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Pancreatic Neoplasms: HELP
Articles by Rachael Stolzenberg-Solomon
Based on 23 articles published since 2009
(Why 23 articles?)
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Between 2009 and 2019, Rachael Stolzenberg-Solomon wrote the following 23 articles about Pancreatic Neoplasms.
 
+ Citations + Abstracts
1 Clinical Trial Dietary consumption of advanced glycation end products and pancreatic cancer in the prospective NIH-AARP Diet and Health Study. 2015

Jiao, Li / Stolzenberg-Solomon, Rachael / Zimmerman, Thea Palmer / Duan, Zhigang / Chen, Liang / Kahle, Lisa / Risch, Adam / Subar, Amy F / Cross, Amanda J / Hollenbeck, Albert / Vlassara, Helen / Striker, Gary / Sinha, Rashmi. ·From the Sections of Gastroenterology and Hepatology (LJ and LC) and Health Services Research (LJ, ZD, and LC), Department of Medicine, Baylor College of Medicine, Houston, TX · the Nutritional Epidemiology Branch, Division of Cancer Epidemiology and Genetics (RS-S and RS) and the Applied Research Program, Division of Cancer Control and Population Sciences (AFS), National Cancer Institute, NIH, Rockville, MD · Westat, Rockville, MD (TPZ) · Information Management Services, Rockville, MD (LK and AR) · the Department of Epidemiology and Biostatistics, School of Public Health, Faculty of Medicine, Imperial College London, London, United Kingdom (AJC) · the Division of Experimental Diabetes and Aging, Mount Sinai School of Medicine, New York, NY (HV and GS) · and AARP, Washington, DC (AH). ·Am J Clin Nutr · Pubmed #25527756.

ABSTRACT: BACKGROUND: Advanced glycation end products (AGEs) are a heterogeneous group of compounds present in uncooked foods as well as in foods cooked at high temperatures. AGEs have been associated with insulin resistance, oxidative stress, and chronic inflammation in patients with diabetes. Dietary AGEs are an important contributor to the AGE pool in the body. N(ϵ)-(carboxymethyl)lysine (CML) AGE is one of the major biologically and chemically well-characterized AGE markers. The consumption of red meat, which is CML-AGE rich, has been positively associated with pancreatic cancer in men. OBJECTIVES: With the use of a published food CML-AGE database, we estimated the consumption of CML AGE in the prospective NIH-AARP Diet and Health Study and evaluated the association between CML-AGE consumption and pancreatic cancer and the mediating effect of CML AGE on the association between red meat consumption and pancreatic cancer. DESIGN: Multivariate Cox proportional hazard regression models were used to estimate HRs and 95% CIs for pancreatic cancer. RESULTS: During an average of 10.5 y of follow-up, we identified 2193 pancreatic cancer cases (1407 men and 786 women) from 528,251 subjects. With the comparison of subjects in the fifth and the first quintiles of CML-AGE consumption, we observed increased pancreatic cancer risk in men (HR: 1.43; 95% CI: 1.06, 1.93, P-trend = 0.003) but not women (HR: 1.14; 95% CI: 0.76, 1.72, P-trend = 0.42). Men in the highest quintile of red meat consumption had higher risk of pancreatic cancer (HR: 1.35; 95% CI: 1.07, 1.70), which attenuated after adjustment for CML-AGE consumption (HR: 1.20; 95% CI: 0.95, 1.53). CONCLUSION: Dietary CML-AGE consumption was associated with modestly increased risk of pancreatic cancer in men and may partially explain the positive association between red meat and pancreatic cancer.

2 Article Serum selenium and pancreatic cancer: a prospective study in the Prostate, Lung, Colorectal and Ovarian Cancer Trial cohort. 2019

Chatterjee, Sharmila / Combs, Gerald F / Chattopadhyay, Amit / Stolzenberg-Solomon, Rachael. ·Metabolic Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, 9609 Medical Center Drive, Rockville, MD, 20850, USA. sharmilahotmail@hotmail.com. · Grand Forks Human Nutrition Research Center, 2420 2nd Ave N, ARS/USDA, Grand Forks, ND, 58203, USA. · School of Dental Medicine, Case Western Reserve University, Cleveland, OH, 44106, USA. · La Trobe, La Trobe University Rural Health School, Melbourne, Australia. · Metabolic Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, 9609 Medical Center Drive, Rockville, MD, 20850, USA. rs221z@nih.gov. ·Cancer Causes Control · Pubmed #30915619.

ABSTRACT: PURPOSE: Pancreatic cancer(PCa) is one of the most lethal cancers with few known consistent nutrition-related risk factors. Epidemiologic associations between the trace element selenium and PCa are inconsistent. This study examined the association of pre-diagnostic serum selenium with incident PCa. METHODS: We conducted a nested case-control study within the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Study (PLCO) cohort of men and women 55-70 years old at baseline (1993-2001). In total, 303 PCa cases developed during the 17-year follow-up period (1993-2009). We selected two controls (n = 606) for each case who were alive at the time the case was diagnosed who were matched on age, sex, race, and date of blood draw. We used conditional logistic regression analysis to calculate the odds ratio (OR) and 95% confidence intervals (CI) adjusting for smoking status and diabetes mellitus. RESULTS: Mean serum selenium concentrations were slightly lower in cases (mean, 95% CI: 139.0 ng/ml, 135.6-138.9) compared to controls (142.5 ng/ml, 140.4-142.4, p = 0.08). Overall, serum selenium was not associated with PCa risk (continuous OR: 0.66; 0.32-1.37). There was no significant interaction by sex, smoking, diabetes, or follow-up time (p > 0.05). CONCLUSION: Our results do not support the hypothesis that serum selenium is associated with PCa risk.

3 Article The Association of Recently Diagnosed Diabetes and Long-term Diabetes With Survival in Pancreatic Cancer Patients: A Pooled Analysis. 2018

Jeon, Christie Y / Li, Donghui / Cleary, Sean / Stolzenberg-Solomon, Rachael / Bosetti, Cristina / La Vecchia, Carlo / Porta, Miquel / Toriola, Adetunji T / Hung, Rayjean J / Kurtz, Robert C / Olson, Sara H. · ·Pancreas · Pubmed #29401167.

ABSTRACT: OBJECTIVES: It is unclear whether long-standing diabetes or new-onset pancreatogenic diabetes contributes to poor prognosis in patients with pancreatic ductal adenocarcinoma (PDAC). METHODS: We investigated the influence of diabetes diagnosed shortly before PDAC and long-term diabetes on overall survival in 2792 PDAC patients who had participated in 3 PDAC case-control studies in the Pancreatic Cancer Case-Control Consortium. There were 300 patients with long-term diabetes of more than 3 years' duration (11%) and 418 patients with recently diagnosed diabetes of 3-year duration or less (15%). We performed Cox regression to determine the association of long-term diabetes and recently diagnosed diabetes with overall survival, adjusting for study site, age, sex, race, stage of disease, surgery, chemotherapy, smoking history, and body mass index at diagnosis. RESULTS: In the overall population, neither long-term diabetes (hazard ratio [HR], 1.10; 95% confidence interval [CI], 0.97-1.26) nor recently diagnosed diabetes (HR, 1.06; 95% CI, 0.94-1.18) was associated with shorter survival. When stratified by stage of disease, long-term diabetes was associated with 42% increase in rate of death in persons with resectable PDAC (HR, 1.42; 95% CI, 1.13-1.78), whereas it was not associated with survival in PDAC patients with more advanced disease. CONCLUSION: Long-term diabetes was associated with increased rate of death in patients with resectable PDAC.

4 Article Pancreatic cancer incidence trends: evidence from the Surveillance, Epidemiology and End Results (SEER) population-based data. 2018

Gordon-Dseagu, Vanessa L / Devesa, Susan S / Goggins, Michael / Stolzenberg-Solomon, Rachael. ·Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, MD 20850, USA. · The Johns Hopkins Hospital, Baltimore, MD 21287, USA. ·Int J Epidemiol · Pubmed #29149259.

ABSTRACT: Background: Annual pancreatic cancer incidence rates have been increasing. We examine pancreatic cancer incidence trends by demographics and histologic type. Methods: Data from the Surveillance, Epidemiology and End Results (SEER) registries were available to assess temporal trends and pancreatic cancer rates from 1974 to 2013. Results: Pancreatic cancer incidence rates declined between the 1970s and 1990s but increased from 1994 to 2013 among White males. Among non-Hispanic White and Hispanic males, the annual percent change (APC) in incidence between 1992 and 2013 was 0.84% and 0.73%, respectively. Rates also rose among White non-Hispanic, Hispanic and Asian females (APC = 0.81%, 0.56% and 1.23%, respectively) and even more rapidly among females aged 25-34 years (APC > 2.5%). Rates among Black males and females remained unchanged, but higher compared with the other racial/ethnic groups. By histologic type, the increases were greatest for non-secretory endocrine cancers ( > 6%), followed by ductal adenocarcinomas (∼5%) and adenocarcinoma, NOS (∼1.4%)-the largest histologic subgroup of pancreatic cancer. Rates for mucinous adenocarcinomas and poorly specified pancreatic cancer decreased. Overall, incidence rates during 2000-13 were higher among males than females [MF incidence rate ratio (IRR) = 1.28]. The IRR was >1.00 at all ages ≥ 35, but rates among females were higher at younger ages (IRRs 15-24: 0.66, 25-34: 0.81). The MF IRRs for most of the histologic types were elevated among males apart from solid pseudopapillary adenocarcinoma and cystic carcinomas (IRR = 0.22, confidence interval: 0.14-0.34 and 0.52, 0.41-0.65, respectively). Conclusion: Pancreatic cancer has been increasing overall, but patterns differ by demographic group and histologic type. Many of the trends parallel changing prevalence of lifestyle risk factors such as smoking, overweight and obesity, and diabetes in the USA, particularly for pancreatic adenocarcinoma, and improved diagnosis methods during the past 40 years.

5 Article Human oral microbiome and prospective risk for pancreatic cancer: a population-based nested case-control study. 2018

Fan, Xiaozhou / Alekseyenko, Alexander V / Wu, Jing / Peters, Brandilyn A / Jacobs, Eric J / Gapstur, Susan M / Purdue, Mark P / Abnet, Christian C / Stolzenberg-Solomon, Rachael / Miller, George / Ravel, Jacques / Hayes, Richard B / Ahn, Jiyoung. ·Department of Population Health, New York University School of Medicine, New York, New York, USA. · Departments of Public Health Sciences and Oral Health Sciences, Biomedical Informatics Center, Program for Human Microbiome Research, Medical University of South Carolina, Charleston, South Carolina, USA. · Epidemiology Research Program, American Cancer Society, Atlanta, Georgia, USA. · Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, USA. · Department of Surgery, New York University School of Medicine, New York, New York, USA. · Department of Cell Biology, New York University School of Medicine, New York, New York, USA. · NYU Perlmutter Cancer Center, New York, New York, USA. · Institute for Genome Sciences, University of Maryland School of Medicine, Baltimore, Maryland, USA. ·Gut · Pubmed #27742762.

ABSTRACT: OBJECTIVE: A history of periodontal disease and the presence of circulating antibodies to selected oral pathogens have been associated with increased risk of pancreatic cancer; however, direct relationships of oral microbes with pancreatic cancer have not been evaluated in prospective studies. We examine the relationship of oral microbiota with subsequent risk of pancreatic cancer in a large nested case-control study. DESIGN: We selected 361 incident adenocarcinoma of pancreas and 371 matched controls from two prospective cohort studies, the American Cancer Society Cancer Prevention Study II and the National Cancer Institute Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial. From pre-diagnostic oral wash samples, we characterised the composition of the oral microbiota using bacterial 16S ribosomal RNA (16S rRNA) gene sequencing. The associations between oral microbiota and risk of pancreatic cancer, controlling for the random effect of cohorts and other covariates, were examined using traditional and L1-penalised least absolute shrinkage and selection operator logistic regression. RESULTS: Carriage of oral pathogens, CONCLUSIONS: This study provides supportive evidence that oral microbiota may play a role in the aetiology of pancreatic cancer.

6 Article Prediagnosis Circulating Insulin-Like Growth Factors and Pancreatic Cancer Survival. 2017

Toriola, Adetunji T / Ziegler, Mark / Li, Yize / Pollak, Michael / Stolzenberg-Solomon, Rachael. ·Department of Surgery, Division of Public Health Sciences, and Siteman Cancer Center, Washington University School of Medicine, St. Louis, MO, USA. a.toriola@wustl.edu. · Department of Surgery, Division of Public Health Sciences, and Siteman Cancer Center, Washington University School of Medicine, St. Louis, MO, USA. · Department of Oncology, McGill University, Montreal, Canada. · Branch of Nutritional Epidemiology, Division of Cancer Epidemiology and Genetics, Department of Health and Human Services, National Cancer Institute, National Institutes of Health, Rockville, MD, USA. ·Ann Surg Oncol · Pubmed #28681154.

ABSTRACT: BACKGROUND: Prediagnosis obesity and diabetes are associated with survival from pancreatic cancer, but the underlying mechanisms have not been characterized. Because both are associated with dysregulation in circulating insulin-like growth factor (IGF) levels, we evaluated the associations of prediagnosis IGF levels (IGF-I, IGF-II) and IGF binding protein 3 (IGFBP-3) with pancreatic cancer survival. METHODS: Participants were subjects enrolled in the intervention arm of the PLCO Cancer Screening Trial who developed exocrine pancreatic cancer during follow-up (N = 178, 116 men and 67 women). Participants provided blood samples at enrollment, before cancer diagnosis. Cox proportional hazards regression model, adjusted for confounders was used to investigate associations of IGF biomarkers with pancreatic cancer survival. Because of the well-documented, gender-specific differences in circulating IGF biomarkers, and differential associations of IGF biomarkers with mortality, we evaluated associations separately among males and females. RESULTS: Median survival was 172 days. Higher IGF-II and IGFBP-3 levels were associated with pancreatic cancer survival among males but not among females. The hazard ratios (HR) of death among men in the highest tertiles of IGF-II and IGFBP-3 compared with men in the lowest tertiles were 0.40 (95% confidence interval (CI) 0.23-0.71, p < 0.01) and 0.59 (95% CI 0.35-0.97, p = 0.10), respectively. There were no statistically significant associations between IGF-I concentrations, IGF-I/IGFBP-3, and pancreatic cancer survival. CONCLUSIONS: Higher prediagnosis circulating IGF-II and IGFBP-3 levels are associated with better pancreatic cancer survival among men but not women. A greater understanding of how IGF signaling is related to pancreatic cancer survival could have utility in improving pancreatic cancer prognosis.

7 Article A Cohort Study of Adolescent and Midlife Diet and Pancreatic Cancer Risk in the NIH-AARP Diet and Health Study. 2017

Gordon-Dseagu, Vanessa L Z / Thompson, Frances E / Subar, Amy F / Ruder, Elizabeth H / Thiébaut, Anne C M / Potischman, Nancy / Stolzenberg-Solomon, Rachael. · ·Am J Epidemiol · Pubmed #28459946.

ABSTRACT: Given the long latency period of pancreatic cancer, exploring the influence of early and midlife exposures will further advance our understanding of the disease. We assessed associations between diet and pancreatic cancer incidence in the National Institutes of Health (NIH)-AARP (formerly American Association of Retired Persons) Diet and Health Study. In 1996, a total of 303,094 participants completed 2 food frequency questionnaires that assessed diet at ages 12-13 years and 10 years previously. We used Cox proportional hazards regression to estimate adjusted hazard ratios and 95% confidence intervals. Through the end of 2006, a total of 1,322 pancreatic cancer cases occurred (average follow up time = 10.1 years). When comparing the highest tertiles with the lowest, carbohydrate intake during adolescence (hazard ratio (HR) = 0.87, 95% confidence interval (CI): 0.76, 0.99), but not 10 years before baseline, was inversely associated with pancreatic cancer risk. Total fat intake 10 years before baseline was significantly associated with increased risk (HR = 1.17, 95% CI: 1.02, 1.34), while risk was higher for high fat intake during both adolescence and midlife. Calcium intake 10 years before baseline was associated with reduced risk (HR = 0.87, 95% CI: 0.76, 0.99), as was a change from low intake in adolescence to high intake in midlife (HR = 0.71, 95% CI: 0.54, 0.93). Our study found a number of dietary factors present during adolescence and midlife to be associated with pancreatic cancer.

8 Article No Association Between Nonsteroidal Anti-inflammatory Drug Use and Pancreatic Cancer Incidence and Survival. 2017

Lad, Alisha A / Ma, Yinjiao / Lee, Jung Ae / Park, Yikyung / Liao, Linda M / Stolzenberg-Solomon, Rachael / Toriola, Adetunji T. ·Department of Surgery, Division of Public Health Sciences, Siteman Cancer Center, Washington University School of Medicine, St. Louis, MO; Metabolic Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institute of Health Bethesda, MD; Department of Surgery, Division of Public Health Sciences, Siteman Cancer Center, Washington University School of Medicine, St. Louis, MO. a.toriola@wustl.edu. ·Pancreas · Pubmed #28426499.

ABSTRACT: -- No abstract --

9 Article Helicobacter pylori infection, chronic corpus atrophic gastritis and pancreatic cancer risk in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort: A nested case-control study. 2017

Huang, Jiaqi / Zagai, Ulrika / Hallmans, Göran / Nyrén, Olof / Engstrand, Lars / Stolzenberg-Solomon, Rachael / Duell, Eric J / Overvad, Kim / Katzke, Verena A / Kaaks, Rudolf / Jenab, Mazda / Park, Jin Young / Murillo, Raul / Trichopoulou, Antonia / Lagiou, Pagona / Bamia, Christina / Bradbury, Kathryn E / Riboli, Elio / Aune, Dagfinn / Tsilidis, Konstantinos K / Capellá, Gabriel / Agudo, Antonio / Krogh, Vittorio / Palli, Domenico / Panico, Salvatore / Weiderpass, Elisabete / Tjønneland, Anne / Olsen, Anja / Martínez, Begoña / Redondo-Sanchez, Daniel / Chirlaque, Maria-Dolores / Hm Peeters, Petra / Regnér, Sara / Lindkvist, Björn / Naccarati, Alessio / Ardanaz, Eva / Larrañaga, Nerea / Boutron-Ruault, Marie-Christine / Rebours, Vinciane / Barré, Amélie / Bueno-de-Mesquita, H B As / Ye, Weimin. ·Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Solna, Sweden. · Department of Public Health and Clinical Nutrition, Umeå University, Umeå, Sweden. · Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, Stockholm, Sweden. · Metabolic Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Rockville, MD. · Unit of Nutrition and Cancer, Cancer Epidemiology Research Program, Catalan Institute of Oncology (ICO-IDIBELL), Barcelona, Spain. · Department of Public Health, Section for Epidemiology, Aarhus University, Aarhus, Denmark. · Division of Cancer Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Germany. · Prevention and Implementation Group, Section of Early Detection and Prevention, Section of Nutrition and Metabolism, International Agency for Research on Cancer, Lyon, France. · Hellenic Health Foundation, Athens, Greece. · WHO Collaborating Center for Nutrition and Health, Unit of Nutritional Epidemiology and Nutrition in Public Health, Department of Hygiene, Epidemiology and Medical Statistics, School of Medicine, National and Kapodistrian University of Athens, Athens, Greece. · Department of Epidemiology, Harvard T. H. Chan School of Public Health, Boston, MA. · Cancer Epidemiology Unit, Nuffield Department of Population Health, University of Oxford, Oxford, United Kingdom. · Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London, United Kingdom. · Department of Hygiene and Epidemiology, University of Ioannina School of Medicine, Ioannina, Greece. · Translational Research Laboratory, IDIBELL-Catalan Institute of Oncology, Barcelona, Spain. · Unit of Nutrition and Cancer. Cancer Epidemiology Research Program. Catalan Institute of Oncology-IDIBELL. L'Hospitalet de Llobregat, Barcelona, Spain. · Epidemiology and Prevention Unit, Fondazione IRCCS Istituto Nazionale dei Tumori, Milano, Italy. · Cancer Risk Factors and Life-Style Epidemiology Unit, Cancer Research and Prevention Institute - ISPO, Florence, Italy. · Dipartimento di medicina clinica e chirurgia Federico II, Naples, Italy. · Department of Community Medicine, University of Tromsø, The Arctic University of Norway, Tromsø, Norway. · Department of Research, Cancer Registry of Norway, Institute of Population-Based Cancer Research, Oslo, Norway. · Genetic Epidemiology Group, Folkhälsan Research Center, Helsinki, Finland. · Danish Cancer Society Research Center, Copenhagen, Denmark. · Andalusian School of Public Health, Instituto De Investigación Biosanitaria Ibs, Granada, Spain. · CIBER of Epidemiology and Public Health (CIBERESP), Madrid, Spain. · Escuela Andaluza de Salud Pública, Instituto de Investigación Biosanitaria ibs, Granada, Hospitales Universitarios de Granada/Universidad de Granada, Granada, Spain. · Department of Epidemiology, Regional Health Council, IMIB-Arrixaca, Murcia, Spain. · Department of Health and Social Sciences, Universidad de Murcia, Murcia, Spain. · Department of Epidemiology, Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht, The Netherlands. · Department of Surgery, Institution of Clinical Sciences Malmö, Lund University, Malmö, Sweden. · Department of Medicine, Sahlgrenska University Hospital, Gothenburg, Sweden. · Molecular and Genetic Epidemiology Unit, Human Genetics Foundation, Turin, Italy. · Navarra Public Health Institute, Pamplona, Spain; IdiSNA, Navarra Institute for Health Research, Pamplona, Spain. · Public Health Division of Gipuzkoa, Regional Government of the Basque Country, Spain. · Hormones and Women's Health Team, INSERM, Centre for Research in Epidemiology and Population Health (CESP), U1018, Nutrition, Villejuif, F-94805, France. · Université Paris Sud, UMRS 1018, Villejuif, F-94805, France. · Institut Gustave Roussy, Villejuif, F-94805, France. · Department of Gastroenterology and Pancreatology, Beaujon Hospital, University Paris 7, Clichy, France. · Université Paris Sud and Gastroenterology Unit, Hôpitaux Universitaires Paris Sud, CHU de Bicêtre, AP-HP, Le Kremlin Bicêtre, France. · Department for Determinants of Chronic Diseases (DCD), National Institute for Public Health and the Environment (RIVM), Bilthoven, The Netherlands. · Department of Gastroenterology and Hepatology, University Medical Centre, Utrecht, The Netherlands. · Department of Epidemiology and Biostatistics, The School of Public Health, Imperial College London, London, United Kingdom. · Department of Social & Preventive Medicine, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia. · The Medical Biobank at Umeå University, Umeå, Sweden. ·Int J Cancer · Pubmed #28032715.

ABSTRACT: The association between H. pylori infection and pancreatic cancer risk remains controversial. We conducted a nested case-control study with 448 pancreatic cancer cases and their individually matched control subjects, based on the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort, to determine whether there was an altered pancreatic cancer risk associated with H. pylori infection and chronic corpus atrophic gastritis. Conditional logistic regression models were applied to calculate odds ratios (ORs) and corresponding 95% confidence intervals (CIs), adjusted for matching factors and other potential confounders. Our results showed that pancreatic cancer risk was neither associated with H. pylori seropositivity (OR = 0.96; 95% CI: 0.70, 1.31) nor CagA seropositivity (OR = 1.07; 95% CI: 0.77, 1.48). We also did not find any excess risk among individuals seropositive for H. pylori but seronegative for CagA, compared with the group seronegative for both antibodies (OR = 0.94; 95% CI: 0.63, 1.38). However, we found that chronic corpus atrophic gastritis was non-significantly associated with an increased pancreatic cancer risk (OR = 1.35; 95% CI: 0.77, 2.37), and although based on small numbers, the excess risk was particularly marked among individuals seronegative for both H. pylori and CagA (OR = 5.66; 95% CI: 1.59, 20.19, p value for interaction < 0.01). Our findings provided evidence supporting the null association between H. pylori infection and pancreatic cancer risk in western European populations. However, the suggested association between chronic corpus atrophic gastritis and pancreatic cancer risk warrants independent verification in future studies, and, if confirmed, further studies on the underlying mechanisms.

10 Article Functional characterization of a chr13q22.1 pancreatic cancer risk locus reveals long-range interaction and allele-specific effects on DIS3 expression. 2016

Hoskins, Jason W / Ibrahim, Abdisamad / Emmanuel, Mickey A / Manmiller, Sarah M / Wu, Yinglun / O'Neill, Maura / Jia, Jinping / Collins, Irene / Zhang, Mingfeng / Thomas, Janelle V / Rost, Lauren M / Das, Sudipto / Parikh, Hemang / Haake, Jefferson M / Matters, Gail L / Kurtz, Robert C / Bamlet, William R / Klein, Alison / Stolzenberg-Solomon, Rachael / Wolpin, Brian M / Yarden, Ronit / Wang, Zhaoming / Smith, Jill / Olson, Sara H / Andresson, Thorkell / Petersen, Gloria M / Amundadottir, Laufey T. ·Laboratory of Translational Genomics, Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA. · Protein Characterization Laboratory, Frederick National Laboratory for Cancer Research, Frederick, MD, USA. · Department of Epidemiology and Biostatistics, Memorial Sloan-Kettering Cancer Center, New York, NY, USA. · Department of Human Science, NHS, Georgetown University Medical Center, NW, Washington DC, USA. · Department of Biochemistry and Molecular Biology, The Pennsylvania State University College of Medicine, Hershey, PA, USA. · Department of Medicine, Memorial Sloan-Kettering Cancer Center, New York, New York, USA. · Department of Health Sciences Research, Mayo Clinic, Rochester, Minnesota, USA. · Department of Oncology, the Johns Hopkins University School of Medicine, Baltimore, Maryland, USA · Department of Epidemiology, the Bloomberg School of Public Health, Baltimore, Maryland, USA · Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA. · Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts, USA. · Department of Computational Biology, St. Jude Children’s Research Hospital, Memphis, TN, USA · Department of Medicine, Georgetown University Hospital, Washington, DC, and Department of Medicine, Penn State University College of Medicine, Hershey PA, USA. ·Hum Mol Genet · Pubmed #28172817.

ABSTRACT: Genome-wide association studies (GWAS) have identified multiple common susceptibility loci for pancreatic cancer. Here we report fine-mapping and functional analysis of one such locus residing in a 610 kb gene desert on chr13q22.1 (marked by rs9543325). The closest candidate genes, KLF5, KLF12, PIBF1, DIS3 and BORA, range in distance from 265-586 kb. Sequencing three sub-regions containing the top ranked SNPs by imputation P-value revealed a 30 bp insertion/deletion (indel) variant that was significantly associated with pancreatic cancer risk (rs386772267, P = 2.30 × 10

11 Article Pancreatic Cancer Risk Associated with Prediagnostic Plasma Levels of Leptin and Leptin Receptor Genetic Polymorphisms. 2016

Babic, Ana / Bao, Ying / Qian, Zhi Rong / Yuan, Chen / Giovannucci, Edward L / Aschard, Hugues / Kraft, Peter / Amundadottir, Laufey T / Stolzenberg-Solomon, Rachael / Morales-Oyarvide, Vicente / Ng, Kimmie / Stampfer, Meir J / Ogino, Shuji / Buring, Julie E / Sesso, Howard D / Gaziano, John Michael / Rifai, Nader / Pollak, Michael N / Anderson, Matthew L / Cochrane, Barbara B / Luo, Juhua / Manson, JoAnn E / Fuchs, Charles S / Wolpin, Brian M. ·Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts. · Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital, and Harvard Medical School, Boston, Massachusetts. · Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, Massachusetts. · Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, Massachusetts. · Department of Biostatistics, Harvard T.H. Chan School of Public Health, Boston, Massachusetts. · Laboratory of Translational Genomics, Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, Bethesda, Maryland. · Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, DHHS, Bethesda, Maryland. · Division of MPE Molecular Pathological Epidemiology, Department of Pathology, Brigham and Women's Hospital, Boston, Massachusetts. · Division of Preventive Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts. · Department of Ambulatory Care and Prevention, Harvard Medical School, Boston, Massachusetts. · Massachusetts Veterans Epidemiology Research and Information Center (MAVERIC), VA Boston Healthcare System, Boston, Massachusetts. · Department of Laboratory Medicine, Children's Hospital Boston, Boston, Massachusetts. · Cancer Prevention Research Unit, Department of Oncology, Faculty of Medicine, McGill University, Montreal, Quebec, Canada. · Department of Obstetrics and Gynecology, Baylor College of Medicine, Houston, Texas. · University of Washington School of Nursing, Seattle, Washington. · Department of Community Medicine, West Virginia University, Morgantown, West Virginia. · Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts. bwolpin@partners.org. ·Cancer Res · Pubmed #27780823.

ABSTRACT: Leptin is an adipokine involved in regulating energy balance, which has been identified as a potential biologic link in the development of obesity-associated cancers, such as pancreatic cancer. In this prospective, nested case-control study of 470 cases and 1,094 controls from five U.S. cohorts, we used conditional logistic regression to evaluate pancreatic cancer risk by prediagnostic plasma leptin, adjusting for race/ethnicity, diabetes, body mass index, physical activity, plasma C-peptide, adiponectin, and 25-hydroxyvitamin D. Because of known differences in leptin levels by gender, analyses were conducted separately for men and women. We also evaluated associations between 32 tagging SNPs in the leptin receptor (LEPR) gene and pancreatic cancer risk. Leptin levels were higher in female versus male control participants (median, 20.8 vs. 6.7 ng/mL; P < 0.0001). Among men, plasma leptin was positively associated with pancreatic cancer risk and those in the top quintile had a multivariable-adjusted OR of 3.02 [95% confidence interval (CI), 1.27-7.16; P

12 Article Association of Common Susceptibility Variants of Pancreatic Cancer in Higher-Risk Patients: A PACGENE Study. 2016

Childs, Erica J / Chaffee, Kari G / Gallinger, Steven / Syngal, Sapna / Schwartz, Ann G / Cote, Michele L / Bondy, Melissa L / Hruban, Ralph H / Chanock, Stephen J / Hoover, Robert N / Fuchs, Charles S / Rider, David N / Amundadottir, Laufey T / Stolzenberg-Solomon, Rachael / Wolpin, Brian M / Risch, Harvey A / Goggins, Michael G / Petersen, Gloria M / Klein, Alison P. ·Department of Oncology, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins School of Medicine, Baltimore, Maryland. · Department of Health Sciences Research, Mayo Clinic College of Medicine, Rochester, Minnesota. · Lunenfeld-Tanenbaum Research Institute of Mount Sinai Hospital, Toronto, Ontario, Canada. · Population Sciences Division, Dana-Farber Cancer Institute, and Gastroenterology Division, Brigham and Women's Hospital, Boston, Massachusetts. · Department of Oncology, Karmanos Cancer Institute and Wayne State University, Detroit, Michigan. · Baylor College of Medicine, Dan L. Duncan Cancer Center, Houston, Texas. · Department of Oncology, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins School of Medicine, Baltimore, Maryland. Department of Pathology, Sol Goldman Pancreatic Cancer Research Center, Johns Hopkins School of Medicine, Baltimore, Maryland. · Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, U.S. Department of Health and Human Services, Bethesda, Maryland. · Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts. Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts. · Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts. Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts. · Department of Chronic Disease Epidemiology, Yale School of Public Health, New Haven, Connecticut. · Department of Pathology, Sol Goldman Pancreatic Cancer Research Center, Johns Hopkins School of Medicine, Baltimore, Maryland. · Department of Oncology, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins School of Medicine, Baltimore, Maryland. Department of Pathology, Sol Goldman Pancreatic Cancer Research Center, Johns Hopkins School of Medicine, Baltimore, Maryland. aklein1@jhmi.edu. ·Cancer Epidemiol Biomarkers Prev · Pubmed #27197284.

ABSTRACT: Individuals from pancreatic cancer families are at increased risk, not only of pancreatic cancer, but also of melanoma, breast, ovarian, and colon cancers. While some of the increased risk may be due to mutations in high-penetrance genes (i.e., BRCA2, PALB2, ATM, p16/CDKN2A or DNA mismatch repair genes), common genetic variants may also be involved. In a high-risk population of cases with either a family history of pancreatic cancer or early-onset pancreatic cancer (diagnosis before the age of 50 years), we examined the role of genetic variants previously associated with risk of pancreatic, breast, ovarian, or prostate cancer. We genotyped 985 cases (79 early-onset cases, 906 cases with a family history of pancreatic cancer) and 877 controls for 215,389 SNPs using the iSelect Collaborative Oncological Gene-Environment Study (iCOGS) array with custom content. Logistic regression was performed using a log-linear additive model. We replicated several previously reported pancreatic cancer susceptibility loci, including recently identified variants on 2p13.3 and 7p13 (2p13.3, rs1486134: OR = 1.36; 95% CI, 1.13-1.63; P = 9.29 × 10(-4); 7p13, rs17688601: OR = 0.76; 95% CI, 0.63-0.93; P = 6.59 × 10(-3)). For the replicated loci, the magnitude of association observed in these high-risk patients was similar to that observed in studies of unselected patients. In addition to the established pancreatic cancer loci, we also found suggestive evidence of association (P < 5 × 10(-5)) to pancreatic cancer for SNPs at HDAC9 (7p21.1) and COL6A2 (21q22.3). Even in high-risk populations, common variants influence pancreatic cancer susceptibility. Cancer Epidemiol Biomarkers Prev; 25(7); 1185-91. ©2016 AACR.

13 Article Are meat and heme iron intake associated with pancreatic cancer? Results from the NIH-AARP diet and health cohort. 2016

Taunk, Pulkit / Hecht, Eric / Stolzenberg-Solomon, Rachael. ·Department of Public Health Sciences, University of Miami Miller School of Medicine, Miami, FL. · Division of Cancer Epidemiology and Genetics, Department of Health and Human Services, National Cancer Institute, National Institutes of Health, Rockville, MD. ·Int J Cancer · Pubmed #26666579.

ABSTRACT: Several studies on pancreatic cancer have reported significant positive associations for intake of red meat but null associations for heme iron. We assessed total, red, white and processed meat intake, meat cooking methods and doneness and heme iron and mutagen intake in relation to pancreatic cancer in the NIH-AARP Diet and Health Study cohort. A total of 322,846 participants (187,265 men and 135,581 women) successfully completed and returned the food frequency questionnaire between 1995 and 1996. After a mean follow-up of 9.2 years (up to 10.17 years), 1,417 individuals (895 men and 522 women) developed exocrine pancreatic cancer. Cox proportional hazard models were used to calculate hazard ratios (HRs) and 95% confidence intervals (CIs), and trends were calculated using the median value of each quantile. Models incorporated age as the time metric and were adjusted for smoking history, body mass index, self-reported diabetes and energy-adjusted saturated fat. Pancreatic cancer risk significantly increased with intake of total meat (Q5 vs. Q1: HR = 1.20, 95% CI 1.02-1.42, p-trend = 0.03), red meat (HR = 1.22, 95% CI 1.01-1.48, p-trend = 0.02), high-temperature cooked meat (HR = 1.21, 95% CI 1.00-1.45, p-trend = 0.02), grilled/barbequed meat (HR = 1.24, 95% CI 1.03-1.50, p-trend = 0.007), well/very well done meat (HR = 1.32, 95% CI 1.10-1.58, p-trend = 0.005) and heme iron from red meat (Q4 vs. Q1: HR = 1.21, 95% CI 1.01-1.45, p-trend = 0.04). When stratified by sex, these associations remained significant in men but not women except for white meat intake in women (HR = 1.33, 95% CI 1.02-1.74, p-trend = 0.04). Additional studies should confirm our findings that consuming heme iron from red meat increases pancreatic cancer risk.

14 Article TERT gene harbors multiple variants associated with pancreatic cancer susceptibility. 2015

Campa, Daniele / Rizzato, Cosmeri / Stolzenberg-Solomon, Rachael / Pacetti, Paola / Vodicka, Pavel / Cleary, Sean P / Capurso, Gabriele / Bueno-de-Mesquita, H B As / Werner, Jens / Gazouli, Maria / Butterbach, Katja / Ivanauskas, Audrius / Giese, Nathalia / Petersen, Gloria M / Fogar, Paola / Wang, Zhaoming / Bassi, Claudio / Ryska, Miroslav / Theodoropoulos, George E / Kooperberg, Charles / Li, Donghui / Greenhalf, William / Pasquali, Claudio / Hackert, Thilo / Fuchs, Charles S / Mohelnikova-Duchonova, Beatrice / Sperti, Cosimo / Funel, Niccola / Dieffenbach, Aida Karina / Wareham, Nicholas J / Buring, Julie / Holcátová, Ivana / Costello, Eithne / Zambon, Carlo-Federico / Kupcinskas, Juozas / Risch, Harvey A / Kraft, Peter / Bracci, Paige M / Pezzilli, Raffaele / Olson, Sara H / Sesso, Howard D / Hartge, Patricia / Strobel, Oliver / Małecka-Panas, Ewa / Visvanathan, Kala / Arslan, Alan A / Pedrazzoli, Sergio / Souček, Pavel / Gioffreda, Domenica / Key, Timothy J / Talar-Wojnarowska, Renata / Scarpa, Aldo / Mambrini, Andrea / Jacobs, Eric J / Jamroziak, Krzysztof / Klein, Alison / Tavano, Francesca / Bambi, Franco / Landi, Stefano / Austin, Melissa A / Vodickova, Ludmila / Brenner, Hermann / Chanock, Stephen J / Delle Fave, Gianfranco / Piepoli, Ada / Cantore, Maurizio / Zheng, Wei / Wolpin, Brian M / Amundadottir, Laufey T / Canzian, Federico. ·Division of Cancer Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Germany. · Genomic Epidemiology Group, German Cancer Research Center (DKFZ), Heidelberg, Germany. · Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, MD. · Oncology Department, ASL1 Massa Carrara, Massa Carrara, Italy. · Department of Molecular Biology of Cancer, Institute of Experimental Medicine, Academy of Science of Czech Republic, Prague, Czech Republic. · Department of Surgery, University Health Network, University of Toronto, Toronto, ON, Canada. · Digestive and Liver Disease Unit, S. Andrea Hospital, 'Sapienza' University of Rome, Rome, Italy. · Department of Determinants of Chronic Diseases (DCD), National Institute for Public Health and the Environment (RIVM), Bilthoven, The Netherlands. · Department of Gastroenterology and Hepatology, University Medical Centre, Utrecht, The Netherlands. · Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London, United Kingdom. · Department of Social and Preventive Medicine, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia. · Department of General Surgery, University Hospital Heidelberg, Heidelberg, Germany. · Department of Basic Medical Science, Laboratory of Biology, School of Medicine, University of Athens, Athens, Greece. · Division of Clinical Epidemiology and Aging Research, German Cancer Research Center (DKFZ), Heidelberg, Germany. · Department of Gastroenterology, Lithuanian University of Health Sciences, Kaunas, Lithuania. · Department of Health Sciences Research, Mayo Clinic College of Medicine, Rochester, MN. · Department of Laboratory Medicine, University Hospital of Padua, Padua, Italy. · Surgical and Oncological Department, Pancreas Institute - University and Hospital Trust of Verona, Verona, Italy. · Department of Surgery, Second Faculty of Medicine, Charles University in Prague and Central Military Hospital, Prague, Czech Republic. · 1st Department of Propaedeutic Surgery, School of Medicine, University of Athens, Athens, Greece. · Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA. · Department of Gastrointestinal Medical Oncology, University of Texas M.D. Anderson Cancer Center, Houston, TX. · National Institute for Health Research Liverpool Pancreas Biomedical Research Unit, University of Liverpool, Liverpool, United Kingdom. · Department of Surgery, Gastroenterology and Oncology (DISCOG), University of Padua, Padua, Italy. · Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA. · Department of Oncology, Palacky University Medical School and Teaching Hospital in Olomouc, Olomouc, Czech Republic. · Department of Surgery, Unit of Experimental Surgical Pathology, University Hospital of Pisa, Pisa, Italy. · German Cancer Consortium (DKTK), Heidelberg, Germany. · MRC Epidemiology Unit, Institute of Metabolic Science, University of Cambridge, Cambridge, United Kingdom. · Divisions of Preventive Medicine and Aging, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA. · Institute of Hygiene and Epidemiology, First Faculty of Medicine, Charles University in Prague, Prague, Czech Republic. · Department of Medicine - DIMED, University of Padua, Padua, Italy. · Department of Epidemiology and Public Health, Yale School of Public Health, New Haven, CT. · Department of Epidemiology, Harvard School of Public Health, Boston, MA. · Department of Epidemiology and Biostatistics, University of California San Francisco, San Francisco, CA. · Pancreas Unit, Department of Digestive Diseases and Internal Medicine, Sant'Orsola-Malpighi Hospital, Bologna, Italy. · Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, NY. · Department of Digestive Tract Diseases, Medical University of Łodz, Łodz, Poland. · Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD. · Division of Epidemiology, Departments of Obstetrics and Gynecology, Environmental Medicine, and Population Health, New York University School of Medicine, New York, NY. · Surgical Clinic 4, University of Padua, Padua, Italy. · Department of Toxicogenomics, National Institute of Public Health, Prague, Czech Republic. · Division of Gastroenterology and Research Laboratory, IRCCS Scientific Institute and Regional General Hospital "Casa Sollievo Della Sofferenza,", San Giovanni Rotondo, Italy. · Cancer Epidemiology Unit, Nuffield Department of Population Health, University of Oxford, Oxford, United Kingdom. · ARC-NET: Centre for Applied Research on Cancer, University and Hospital Trust of Verona, Verona, Italy. · Epidemiology Research Program, American Cancer Society, Atlanta, GA. · Department of Hematology, Institute of Hematology and Transfusion Medicine, Warsaw, Poland. · Department of Oncology, The Johns Hopkins University School of Medicine, Baltimore, MD. · Blood Transfusion Service, Azienda Ospedaliero Universitaria Meyer, Florence, Italy. · Department of Biology, University of Pisa, Pisa, Italy. · Department of Epidemiology, University of Washington, Seattle, WA. · Department of Medicine and Vanderbilt-Ingram Cancer Center, Vanderbilt University Medical Center, Nashville, TN. ·Int J Cancer · Pubmed #25940397.

ABSTRACT: A small number of common susceptibility loci have been identified for pancreatic cancer, one of which is marked by rs401681 in the TERT-CLPTM1L gene region on chromosome 5p15.33. Because this region is characterized by low linkage disequilibrium, we sought to identify whether additional single nucleotide polymorphisms (SNPs) could be related to pancreatic cancer risk, independently of rs401681. We performed an in-depth analysis of genetic variability of the telomerase reverse transcriptase (TERT) and the telomerase RNA component (TERC) genes, in 5,550 subjects with pancreatic cancer and 7,585 controls from the PANcreatic Disease ReseArch (PANDoRA) and the PanScan consortia. We identified a significant association between a variant in TERT and pancreatic cancer risk (rs2853677, odds ratio = 0.85; 95% confidence interval = 0.80-0.90, p = 8.3 × 10(-8)). Additional analysis adjusting rs2853677 for rs401681 indicated that the two SNPs are independently associated with pancreatic cancer risk, as suggested by the low linkage disequilibrium between them (r(2) = 0.07, D' = 0.28). Three additional SNPs in TERT reached statistical significance after correction for multiple testing: rs2736100 (p = 3.0 × 10(-5) ), rs4583925 (p = 4.0 × 10(-5) ) and rs2735948 (p = 5.0 × 10(-5) ). In conclusion, we confirmed that the TERT locus is associated with pancreatic cancer risk, possibly through several independent variants.

15 Article Variants associated with susceptibility to pancreatic cancer and melanoma do not reciprocally affect risk. 2014

Wu, Lang / Goldstein, Alisa M / Yu, Kai / Yang, Xiaohong Rose / Rabe, Kari G / Arslan, Alan A / Canzian, Federico / Wolpin, Brian M / Stolzenberg-Solomon, Rachael / Amundadottir, Laufey T / Petersen, Gloria M. ·Authors' Affiliations: Department of Health Sciences Research, Mayo Clinic, Rochester, Minnesota; Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, Bethesda, Maryland; Departments of Obstetrics and Gynecology and Environmental Medicine, New York University School of Medicine, New York, New York; Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts; and Genomic Epidemiology Group, German Cancer Research Center (DKFZ), Heidelberg, Germany. · Authors' Affiliations: Department of Health Sciences Research, Mayo Clinic, Rochester, Minnesota; Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, Bethesda, Maryland; Departments of Obstetrics and Gynecology and Environmental Medicine, New York University School of Medicine, New York, New York; Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts; and Genomic Epidemiology Group, German Cancer Research Center (DKFZ), Heidelberg, Germany Petersen.Gloria@mayo.edu. ·Cancer Epidemiol Biomarkers Prev · Pubmed #24642353.

ABSTRACT: BACKGROUND: Melanoma cases may exist in pancreatic cancer kindreds, whereas there is increased risk of pancreatic cancer in familial melanoma. The two cancers may share genetic susceptibility variants in common. METHODS: Three dbGaP (datasets in Genotypes and Phenotypes)-deposited GWAS (genome-wide association study) datasets (MD Anderson melanoma, PanScan 1, and PanScan 2 for pancreatic cancer) were used. Thirty-seven melanoma susceptibility variants in 22 genomic regions from published GWAS, plus melanoma-related genes and pathways were examined for pancreatic cancer risk in the PanScan datasets. Conversely, nine known pancreatic cancer susceptibility variants were examined for melanoma risk in the MD Anderson dataset. RESULTS: In the PanScan data, initial associations were found with melanoma susceptibility variants in NCOA6 [rs4911442; OR, 1.32; 95% confidence interval (CI), 1.03-1.70; P = 0.03], YWHAZP5 (rs17119461; OR, 2.62; 95% CI, 1.08-6.35; P = 0.03), and YWHAZP5 (rs17119490; OR, 2.62; 95% CI, 1.08-6.34; P = 0.03), TYRP1 (P = 0.04), and IFNA13 (P = 0.04). In the melanoma dataset, two pancreatic cancer susceptibility variants were associated: NR5A2 (rs12029406; OR, 1.39; 95% CI, 1.01-1.92; P = 0.04) and CLPTM1L-TERT (rs401681; OR, 1.16; 95% CI, 1.01-1.34; P = 0.04). None of these associations remained significant after correcting for multiple comparisons. CONCLUSION: Reported variants of melanoma genes and pathways do not play a role in pancreatic cancer predisposition. Reciprocally, pancreatic cancer susceptibility variants are not associated with melanoma risk. IMPACT: Known melanoma-related genes and pathways, as well as GWAS-derived susceptibility variants of melanoma and pancreatic cancer, do not explain the shared genetic etiology of these two cancers. Cancer Epidemiol Biomarkers Prev; 23(6); 1121-4. ©2014 AACR.

16 Article A fast multilocus test with adaptive SNP selection for large-scale genetic-association studies. 2014

Zhang, Han / Shi, Jianxin / Liang, Faming / Wheeler, William / Stolzenberg-Solomon, Rachael / Yu, Kai. ·Biostatistics Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD, USA. · Department of Statistics, Texas A&M University, College Station, TX, USA and. · Information Management Services, Inc., Silver Spring, MD, USA. ·Eur J Hum Genet · Pubmed #24022295.

ABSTRACT: As increasing evidence suggests that multiple correlated genetic variants could jointly influence the outcome, a multilocus test that aggregates association evidence across multiple genetic markers in a considered gene or a genomic region may be more powerful than a single-marker test for detecting susceptibility loci. We propose a multilocus test, AdaJoint, which adopts a variable selection procedure to identify a subset of genetic markers that jointly show the strongest association signal, and defines the test statistic based on the selected genetic markers. The P-value from the AdaJoint test is evaluated by a computationally efficient algorithm that effectively adjusts for multiple-comparison, and is hundreds of times faster than the standard permutation method. Simulation studies demonstrate that AdaJoint has the most robust performance among several commonly used multilocus tests. We perform multilocus analysis of over 26,000 genes/regions on two genome-wide association studies of pancreatic cancer. Compared with its competitors, AdaJoint identifies a much stronger association between the gene CLPTM1L and pancreatic cancer risk (6.0 × 10(-8)), with the signal optimally captured by two correlated single-nucleotide polymorphisms (SNPs). Finally, we show AdaJoint as a powerful tool for mapping cis-regulating methylation quantitative trait loci on normal breast tissues, and find many CpG sites whose methylation levels are jointly regulated by multiple SNPs nearby.

17 Article Genome-wide association study of survival in patients with pancreatic adenocarcinoma. 2014

Wu, Chen / Kraft, Peter / Stolzenberg-Solomon, Rachael / Steplowski, Emily / Brotzman, Michelle / Xu, Mousheng / Mudgal, Poorva / Amundadottir, Laufey / Arslan, Alan A / Bueno-de-Mesquita, H Bas / Gross, Myron / Helzlsouer, Kathy / Jacobs, Eric J / Kooperberg, Charles / Petersen, Gloria M / Zheng, Wei / Albanes, Demetrius / Boutron-Ruault, Marie-Christine / Buring, Julie E / Canzian, Federico / Cao, Guangwen / Duell, Eric J / Elena, Joanne W / Gaziano, J Michael / Giovannucci, Edward L / Hallmans, Goran / Hutchinson, Amy / Hunter, David J / Jenab, Mazda / Jiang, Guoliang / Khaw, Kay-Tee / LaCroix, Andrea / Li, Zhaoshen / Mendelsohn, Julie B / Panico, Salvatore / Patel, Alpa V / Qian, Zhi Rong / Riboli, Elio / Sesso, Howard / Shen, Hongbing / Shu, Xiao-Ou / Tjonneland, Anne / Tobias, Geoffrey S / Trichopoulos, Dimitrios / Virtamo, Jarmo / Visvanathan, Kala / Wactawski-Wende, Jean / Wang, Chengfeng / Yu, Kai / Zeleniuch-Jacquotte, Anne / Chanock, Stephen / Hoover, Robert / Hartge, Patricia / Fuchs, Charles S / Lin, Dongxin / Wolpin, Brian M. ·Department of Epidemiology, Harvard School of Public Health, , Boston, Massachusetts, USA. ·Gut · Pubmed #23180869.

ABSTRACT: BACKGROUND AND OBJECTIVE: Survival of patients with pancreatic adenocarcinoma is limited and few prognostic factors are known. We conducted a two-stage genome-wide association study (GWAS) to identify germline variants associated with survival in patients with pancreatic adenocarcinoma. METHODS: We analysed overall survival in relation to single nucleotide polymorphisms (SNPs) among 1005 patients from two large GWAS datasets, PanScan I and ChinaPC. Cox proportional hazards regression was used in an additive genetic model with adjustment for age, sex, clinical stage and the top four principal components of population stratification. The first stage included 642 cases of European ancestry (PanScan), from which the top SNPs (p≤10(-5)) were advanced to a joint analysis with 363 additional patients from China (ChinaPC). RESULTS: In the first stage of cases of European descent, the top-ranked loci were at chromosomes 11p15.4, 18p11.21 and 1p36.13, tagged by rs12362504 (p=1.63×10(-7)), rs981621 (p=1.65×10(-7)) and rs16861827 (p=3.75×10(-7)), respectively. 131 SNPs with p≤10(-5) were advanced to a joint analysis with cases from the ChinaPC study. In the joint analysis, the top-ranked SNP was rs10500715 (minor allele frequency, 0.37; p=1.72×10(-7)) on chromosome 11p15.4, which is intronic to the SET binding factor 2 (SBF2) gene. The HR (95% CI) for death was 0.74 (0.66 to 0.84) in PanScan I, 0.79 (0.65 to 0.97) in ChinaPC and 0.76 (0.68 to 0.84) in the joint analysis. CONCLUSIONS: Germline genetic variation in the SBF2 locus was associated with overall survival in patients with pancreatic adenocarcinoma of European and Asian ancestry. This association should be investigated in additional large patient cohorts.

18 Article Coffee, tea, and sugar-sweetened carbonated soft drink intake and pancreatic cancer risk: a pooled analysis of 14 cohort studies. 2012

Genkinger, Jeanine M / Li, Ruifeng / Spiegelman, Donna / Anderson, Kristin E / Albanes, Demetrius / Bergkvist, Leif / Bernstein, Leslie / Black, Amanda / van den Brandt, Piet A / English, Dallas R / Freudenheim, Jo L / Fuchs, Charles S / Giles, Graham G / Giovannucci, Edward / Goldbohm, R Alexandra / Horn-Ross, Pamela L / Jacobs, Eric J / Koushik, Anita / Männistö, Satu / Marshall, James R / Miller, Anthony B / Patel, Alpa V / Robien, Kim / Rohan, Thomas E / Schairer, Catherine / Stolzenberg-Solomon, Rachael / Wolk, Alicja / Ziegler, Regina G / Smith-Warner, Stephanie A. ·Mailman School of Public Health, 722 w 168th St, Rm 803, New York, NY 10032, USA. jg3081@columbia.edu ·Cancer Epidemiol Biomarkers Prev · Pubmed #22194529.

ABSTRACT: BACKGROUND: Coffee has been hypothesized to have pro- and anticarcinogenic properties, whereas tea may contain anticarcinogenic compounds. Studies assessing coffee intake and pancreatic cancer risk have yielded mixed results, whereas findings for tea intake have mostly been null. Sugar-sweetened carbonated soft drink (SSB) intake has been associated with higher circulating levels of insulin, which may promote carcinogenesis. Few prospective studies have examined SSB intake and pancreatic cancer risk; results have been heterogeneous. METHODS: In this pooled analysis from 14 prospective cohort studies, 2,185 incident pancreatic cancer cases were identified among 853,894 individuals during follow-up. Multivariate (MV) study-specific relative risks (RR) and 95% confidence intervals (CI) were calculated using Cox proportional hazards models and then pooled using a random-effects model. RESULTS: No statistically significant associations were observed between pancreatic cancer risk and intake of coffee (MVRR = 1.10; 95% CI, 0.81-1.48 comparing ≥900 to <0 g/d; 237g ≈ 8oz), tea (MVRR = 0.96; 95% CI, 0.78-1.16 comparing ≥400 to 0 g/d; 237g ≈ 8oz), or SSB (MVRR = 1.19; 95% CI, 0.98-1.46 comparing ≥250 to 0 g/d; 355g ≈ 12oz; P value, test for between-studies heterogeneity > 0.05). These associations were consistent across levels of sex, smoking status, and body mass index. When modeled as a continuous variable, a positive association was evident for SSB (MVRR = 1.06; 95% CI, 1.02-1.12). CONCLUSION AND IMPACT: Overall, no associations were observed for intakes of coffee or tea during adulthood and pancreatic cancer risk. Although we were only able to examine modest intake of SSB, there was a suggestive, modest positive association for risk of pancreatic cancer for intakes of SSB.

19 Article Pancreatic cancer risk: associations with meat-derived carcinogen intake in the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial (PLCO) cohort. 2012

Anderson, Kristin E / Mongin, Steven J / Sinha, Rashmi / Stolzenberg-Solomon, Rachael / Gross, Myron D / Ziegler, Regina G / Mabie, Jerome E / Risch, Adam / Kazin, Sally S / Church, Timothy R. ·Division of Epidemiology and Community Health, University of Minnesota School of Public Health, Minneapolis, Minnesota 55454, USA. ·Mol Carcinog · Pubmed #22162237.

ABSTRACT: BACKGROUND: Epidemiological studies report positive associations between high-temperature cooked meat intake and pancreatic cancer. We assessed associations between dietary intake of heterocyclic amines (HCAs) and benzo(a)pyrene (BaP)-mutagens formed in meat cooked at high temperatures-and incident exocrine pancreatic cancer in a prospective cohort. METHODS: The 62 581 subjects randomized to screening in the Prostate, Lung, Colorectal, and Ovarian Screening Trial (PLCO) who completed an initial dietary survey that assessed meat intake, cooking methods, and doneness preferences defined the cohort. Subjects were surveyed annually for incident cancers through 2007. A National Cancer Institute research database (CHARRED) was used to estimate HCA and BaP intake and a Mutagenic Activity Index (MAI) from survey data. Proportional hazard ratios (HRs) for risk of pancreatic cancer were estimated from multi-variate Cox regression models by quintile of intake, with the lowest quintile as the referent. RESULTS: During follow-up (median: 10 yr), 248 cases of exocrine pancreatic cancer were confirmed. Preferences for well and very well done meat were generally associated with increased risks. Significant elevations in pancreatic cancer risk were found in upper quintiles of MAI, and individual mutagens 2-amino-3,4,8-trimethylimidazo[4,5-f]quinoxaline (DiMeIQx) and 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx). Compared to the lowest quintile of MAI, the third and fifth quintiles brought HRs of 1.86 (1.22, 2.85) and 1.87 (1.16, 3.02), respectively. These three exposures exhibited significant (P-trend: 0.01-0.03) positive trends in risk as their levels increased CONCLUSION: Consuming well-done meat cooked at high temperatures, which contains high mutagen levels, appears to confer increased risk of pancreatic cancer.

20 Article A U-shaped relationship between plasma folate and pancreatic cancer risk in the European Prospective Investigation into Cancer and Nutrition. 2011

Chuang, Shu-Chun / Stolzenberg-Solomon, Rachael / Ueland, Per Magne / Vollset, Stein Emil / Midttun, Øivind / Olsen, Anja / Tjønneland, Anne / Overvad, Kim / Boutron-Ruault, Marie-Christine / Morois, Sophie / Clavel-Chapelon, Françoise / Teucher, Birgit / Kaaks, Rudolf / Weikert, Cornelia / Boeing, Heiner / Trichopoulou, Antonia / Benetou, Vassiliki / Naska, Androniki / Jenab, Mazda / Slimani, Nadia / Romieu, Isabelle / Michaud, Dominique S / Palli, Domenico / Sieri, Sabina / Panico, Salvatore / Sacerdote, Carlotta / Tumino, Rosario / Skeie, Guri / Duell, Eric J / Rodriguez, Laudina / Molina-Montes, Esther / Huerta, José Marı A / Larrañaga, Nerea / Gurrea, Aurelio Barricarte / Johansen, Dorthe / Manjer, Jonas / Ye, Weimin / Sund, Malin / Peeters, Petra H M / Jeurnink, Suzanne / Wareham, Nicholas / Khaw, Kay-Tee / Crowe, Francesca / Riboli, Elio / Bueno-de-Mesquita, Bas / Vineis, Paolo. ·School of Public Health, Imperial College London, London, UK. ·Eur J Cancer · Pubmed #21411310.

ABSTRACT: Folate intake has shown an inverse association with pancreatic cancer; nevertheless, results from plasma measurements were inconsistent. The aim of this study is to examine the association between plasma total homocysteine, methionine, folate, cobalamin, pyridoxal 5'-phosphate, riboflavin, flavin mononucleotide and pancreatic cancer risk in the European Prospective Investigation into Cancer and Nutrition (EPIC). We conducted a nested case-control study in the EPIC cohort, which has an average of 9.6 years of follow-up (1992-2006), using 463 incident pancreatic cancer cases. Controls were matched to each case by center, sex, age (± 1 year), date (± 1 year) and time (± 3 h) at blood collection and fasting status. Conditional logistic regression was used to calculate the odds ratios (OR) and 95% confidence intervals (CI), adjusting for education, smoking status, plasma cotinine concentration, alcohol drinking, body mass index and diabetes status. We observed a U-shaped association between plasma folate and pancreatic cancer risk. The ORs for plasma folate ≤ 5, 5-10, 10-15 (reference), 15-20, and > 20 nmol/L were 1.58 (95% CI=0.72-3.46), 1.39 (0.93-2.08), 1.0 (reference), 0.79 (0.52-1.21), and 1.34 (0.89-2.02), respectively. Methionine was associated with an increased risk in men (per quintile increment: OR=1.17, 95% CI=1.00-1.38) but not in women (OR=0.91, 95% CI=0.78-1.07; p for heterogeneity <0.01). Our results suggest a U-shaped association between plasma folate and pancreatic cancer risk in both men and women. The positive association that we observed between methionine and pancreatic cancer may be sex dependent and may differ by time of follow-up. However, the mechanisms behind the observed associations warrant further investigation.

21 Article Correlates of circulating 25-hydroxyvitamin D: Cohort Consortium Vitamin D Pooling Project of Rarer Cancers. 2010

McCullough, Marjorie L / Weinstein, Stephanie J / Freedman, D Michal / Helzlsouer, Kathy / Flanders, W Dana / Koenig, Karen / Kolonel, Laurence / Laden, Francine / Le Marchand, Loic / Purdue, Mark / Snyder, Kirk / Stevens, Victoria L / Stolzenberg-Solomon, Rachael / Virtamo, Jarmo / Yang, Gong / Yu, Kai / Zheng, Wei / Albanes, Demetrius / Ashby, Jason / Bertrand, Kimberly / Cai, Hui / Chen, Yu / Gallicchio, Lisa / Giovannucci, Edward / Jacobs, Eric J / Hankinson, Susan E / Hartge, Patricia / Hartmuller, Virginia / Harvey, Chinonye / Hayes, Richard B / Horst, Ronald L / Shu, Xiao-Ou. ·American Cancer Society, Atlanta, Georgia 30303-1002, USA. marji.mccullough@cancer.org ·Am J Epidemiol · Pubmed #20562191.

ABSTRACT: Low vitamin D status is common globally and is associated with multiple disease outcomes. Understanding the correlates of vitamin D status will help guide clinical practice, research, and interpretation of studies. Correlates of circulating 25-hydroxyvitamin D (25(OH)D) concentrations measured in a single laboratory were examined in 4,723 cancer-free men and women from 10 cohorts participating in the Cohort Consortium Vitamin D Pooling Project of Rarer Cancers, which covers a worldwide geographic area. Demographic and lifestyle characteristics were examined in relation to 25(OH)D using stepwise linear regression and polytomous logistic regression. The prevalence of 25(OH)D concentrations less than 25 nmol/L ranged from 3% to 36% across cohorts, and the prevalence of 25(OH)D concentrations less than 50 nmol/L ranged from 29% to 82%. Seasonal differences in circulating 25(OH)D were most marked among whites from northern latitudes. Statistically significant positive correlates of 25(OH)D included male sex, summer blood draw, vigorous physical activity, vitamin D intake, fish intake, multivitamin use, and calcium supplement use. Significant inverse correlates were body mass index, winter and spring blood draw, history of diabetes, sedentary behavior, smoking, and black race/ethnicity. Correlates varied somewhat within season, race/ethnicity, and sex. These findings help identify persons at risk for low vitamin D status for both clinical and research purposes.

22 Article A combined healthy lifestyle score and risk of pancreatic cancer in a large cohort study. 2009

Jiao, Li / Mitrou, Panagiota N / Reedy, Jill / Graubard, Barry I / Hollenbeck, Albert R / Schatzkin, Arthur / Stolzenberg-Solomon, Rachael. ·Nutritional Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Rockville, MD 20852, USA. jiaol@mail.nih.gov ·Arch Intern Med · Pubmed #19398688.

ABSTRACT: BACKGROUND: Smoking, alcohol use, diet, body mass index (calculated as weight in kilograms divided by height in meters squared), and physical activity have been studied independently in relation to pancreatic cancer. We generated a healthy lifestyle score to investigate their joint effect on risk of pancreatic cancer. METHODS: In the prospective National Institutes of Health-AARP Diet and Health Study, a total of 450 416 participants aged 50 to 71 years completed the baseline food frequency questionnaire (1995-1996) eliciting diet and lifestyle information and were followed up through December 31, 2003. We identified 1057 eligible incident pancreatic cancer cases. Participants were scored on 5 modifiable lifestyle factors as unhealthy (0 points) or healthy (1 point) on the basis of current epidemiologic evidence. Participants received 1 point for each respective lifestyle factor: nonsmoking, limited alcohol use, adherence to the Mediterranean dietary pattern, body mass index (> or =18 and <25), or regular physical activity. A combined score (0-5 points) was calculated by summing the scores of the 5 factors. Cox proportional hazards regression models were used to estimate relative risk (95% confidence interval) for pancreatic cancer. RESULTS: Compared with the lowest combined score (0 points), the highest score (5 points) was associated with a 58% reduction in risk of developing pancreatic cancer in all participants (relative risk, 0.42; 95% confidence interval, 0.26-0.66; P(trend) <.001). Scores of less than 5 points were associated with 27% of pancreatic cancer cases in our population. CONCLUSION: Findings from this large study suggest that having a high score, as opposed to a low score, on an index combining 5 modifiable lifestyle factors substantially reduces the risk of developing pancreatic cancer.

23 Article Glycemic index, carbohydrates, glycemic load, and the risk of pancreatic cancer in a prospective cohort study. 2009

Jiao, Li / Flood, Andrew / Subar, Amy F / Hollenbeck, Albert R / Schatzkin, Arthur / Stolzenberg-Solomon, Rachael. ·Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD 20852, USA. jiaol@mail.nih.gov ·Cancer Epidemiol Biomarkers Prev · Pubmed #19336549.

ABSTRACT: Diets with high glycemic index and glycemic load have been associated with insulin resistance. Insulin resistance has been implicated in the etiology of pancreatic cancer. We prospectively investigated the associations between glycemic index, carbohydrates, glycemic load, and available carbohydrates dietary constituents (starch and simple sugar) intake and the risk of pancreatic cancer. We followed the participants in the NIH-AARP Diet and Health Study from 1995/1996 through December 2003. A baseline self-administered food frequency questionnaire was used to assess the dietary intake and exposure information. A total of 1,151 exocrine pancreatic cancer cases were identified from 482,362 participants after excluding first-year of follow-up. We used multivariate Cox proportional hazards regression models to calculate relative risks (RR) and 95% confidence intervals (95% CI) for pancreatic cancer. There were no associations between glycemic index, total or available carbohydrates, gycemic load, and pancreatic cancer risk. Participants with high free fructose and glucose intake were at a greater risk of developing pancreatic cancer (highest compared with lowest quintile, RR, 1.29; 95% CI, 1.04-1.59; P trend = 0.004 and RR, 1.35; 95% CI, 1.10-1.67; P trend = 0.005, respectively). There were no statistically significant interactions by body mass index, physical activity, or smoking status. Our results do not support an association between glycemic index, total or available carbohydrate intake, and glycemic load and pancreatic cancer risk. The higher risk associated with high free fructose intake needs further confirmation and elucidation.