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Pancreatic Neoplasms: HELP
Articles by Ying Bao
Based on 23 articles published since 2010
(Why 23 articles?)
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Between 2010 and 2020, Ying Bao wrote the following 23 articles about Pancreatic Neoplasms.
 
+ Citations + Abstracts
1 Review Nurses' Health Study Contributions on the Epidemiology of Less Common Cancers: Endometrial, Ovarian, Pancreatic, and Hematologic. 2016

Birmann, Brenda M / Barnard, Mollie E / Bertrand, Kimberly A / Bao, Ying / Crous-Bou, Marta / Wolpin, Brian M / De Vivo, Immaculata / Tworoger, Shelley S. ·Brenda M. Birmann, Ying Bao, Marta Crous-Bou, Immaculata De Vivo, and Shelley S. Tworoger are with the Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA. Mollie E. Barnard is with the Department of Epidemiology, Harvard T. H. Chan School of Public Health, Boston. Kimberly A. Bertrand is with the Slone Epidemiology Center, Boston University, Boston. Brian M. Wolpin is with the Department of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School. ·Am J Public Health · Pubmed #27459458.

ABSTRACT: OBJECTIVES: To review the contributions of the Nurses' Health Study (NHS) to epidemiologic knowledge of endometrial, ovarian, pancreatic, and hematologic cancers. METHODS: We reviewed selected NHS publications from 1976 to 2016, including publications from consortia and other pooled studies. RESULTS: NHS studies on less common cancers have identified novel risk factors, such as a reduced risk of endometrial cancer in women of advanced age at last birth, and have clarified or prospectively confirmed previously reported associations, including an inverse association between tubal ligation and ovarian cancer. Through biomarker research, the NHS has furthered understanding of the pathogenesis of rare cancers, such as the role of altered metabolism in pancreatic cancer risk and survival. NHS investigations have also demonstrated the importance of the timing of exposure, such as the finding of a positive association of early life body fatness, but not of usual adult body mass index, with non-Hodgkin lymphoma risk. CONCLUSIONS: Evidence from the NHS has informed prevention strategies and contributed to improved survival from less common but often lethal malignancies, including endometrial, ovarian, pancreatic, and hematologic cancers.

2 Review Folate intake and risk of pancreatic cancer: pooled analysis of prospective cohort studies. 2011

Bao, Ying / Michaud, Dominique S / Spiegelman, Donna / Albanes, Demetrius / Anderson, Kristin E / Bernstein, Leslie / van den Brandt, Piet A / English, Dallas R / Freudenheim, Jo L / Fuchs, Charles S / Giles, Graham G / Giovannucci, Edward / Goldbohm, R Alexandra / Håkansson, Niclas / Horn-Ross, Pamela L / Jacobs, Eric J / Kitahara, Cari M / Marshall, James R / Miller, Anthony B / Robien, Kim / Rohan, Thomas E / Schatzkin, Arthur / Stevens, Victoria L / Stolzenberg-Solomon, Rachael Z / Virtamo, Jarmo / Wolk, Alicja / Ziegler, Regina G / Smith-Warner, Stephanie A. ·Channing Laboratory, Department of Medicine, Brigham and Women’s Hospital and Harvard Medical School, Boston, MA, USA. ·J Natl Cancer Inst · Pubmed #22034634.

ABSTRACT: BACKGROUND: Epidemiological studies evaluating the association between folate intake and risk of pancreatic cancer have produced inconsistent results. The statistical power to examine this association has been limited in previous studies partly because of small sample size and limited range of folate intake in some studies. METHODS: We analyzed primary data from 14 prospective cohort studies that included 319,716 men and 542,948 women to assess the association between folate intake and risk of pancreatic cancer. Folate intake was assessed through a validated food-frequency questionnaire at baseline in each study. Study-specific relative risks (RRs) and 95% confidence intervals (CIs) were estimated using Cox proportional hazards models and then pooled using a random effects model. All statistical tests were two-sided. RESULTS: During 7-20 years of follow-up across studies, 2195 pancreatic cancers were identified. No association was observed between folate intake and risk of pancreatic cancer in men and women (highest vs lowest quintile: dietary folate intake, pooled multivariable RR = 1.06, 95% CI = 0.90 to 1.25, P(trend) = .47; total folate intake [dietary folate and supplemental folic acid], pooled multivariable RR = 0.96, 95% CI = 0.80 to 1.16, P(trend) = .90). No between-study heterogeneity was observed (for dietary folate, P(heterogeneity) = .15; for total folate, P(heterogeneity) = .22). CONCLUSION: Folate intake was not associated with overall risk of pancreatic cancer in this large pooled analysis.

3 Article Postoperative hepatic arterial infusion chemotherapy improved survival of pancreatic cancer after radical pancreatectomy: a retrospective study. 2018

Wang, Yongchun / Xu, Yongqiang / Zheng, Yinyuan / Bao, Ying / Wang, Ping. ·Department of General Surgery, First People's Hospital affiliated to Huzhou Normal College, Huzhou, Zhejiang Province, People's Republic of China. · Department of Radiology, First People's Hospital affiliated to Huzhou Normal College, Huzhou, Zhejiang Province, People's Republic of China. ·Onco Targets Ther · Pubmed #29503565.

ABSTRACT: Objective: To determine the effect of postoperative hepatic arterial infusion chemotherapy (HAIC) on long-term survival of patients with pancreatic cancer (PC) after radical pancreatectomy. Methods: A total of 87 patients with PC underwent radical pancreatectomy in the First People's Hospital affiliated to Huzhou Normal College between June 2008 and May 2013. Among these patients, after surgery, 43 received two sessions of HAIC followed by four sessions of systemic chemotherapy (HAIC group), while 44 received six sessions of systemic chemotherapy alone (control group). Both the HAIC and systemic chemotherapy regimen included 5-fluorouracil (1,000 mg/m Results: No significant difference in patient characteristics between the two groups was found. No chemotherapy-related deaths were recorded, and no significant difference in toxicities was observed between the two groups. The 5-year disease-free survival probability did not differ between the two groups ( Conclusions: Postoperative HAIC has the potential to prevent hepatic metastases and increase long-term survival probability of patients with PC after radical pancreatectomy.

4 Article Long-term patterns of fasting blood glucose levels and pancreatic cancer incidence. 2018

Keum, NaNa / Ha, Kyoung Hwa / Bao, Ying / Chung, Moon Jae / Kim, Hyeon Chang / Giovannucci, Edward L. ·Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, MA, USA. · Severance Biomedical Science Institute, Yonsei University College of Medicine, Seoul, Republic of Korea. · Department of Food Science and Biotechnology, Dongguk University, Goyang, Republic of Korea. · Department of Endocrinology and Metabolism, Ajou University School of Medicine, Suwon, Republic of Korea. · Channing Division of Network Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA. · Department of Internal Medicine, Institute of Gastroenterology, Yonsei University College of Medicine, Seoul, Republic of Korea. · Department of Preventive Medicine and Public Health, Yonsei University College of Medicine, 50-1 Yonsei-ro, Seodaemun-gu, Seoul, 03722, Republic of Korea. hckim@yuhs.ac. · Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, USA. · Department of Medicine, Harvard Medical School, Boston, MA, USA. ·Cancer Causes Control · Pubmed #29197995.

ABSTRACT: BACKGROUND: Whether type 2 diabetes is cause or consequence, or both, of pancreatic cancer (PaC) remains unresolved. Leveraging repeated measurements of fasting blood glucose (FBG), we examined the temporal relationship between hyperglycemia and PaC incidence. METHODS: We conducted a nested case-control study of 278 cases and 826 matched-controls from the Korean National Health Insurance Service-Health Screening Cohort. Over 11 years before index date (date of PaC diagnosis for cases), all participants had at least one FBG measurement in each of the three time windows: - 11 to - 8, - 7 to - 4, and - 3 to 0 years. Using conditional logistic regression, we estimated odds ratios(ORs) of PaC and 95% confidence intervals (CIs) for hyperglycemia in the overall period and at each interval; for major long-term patterns of FBG across the three intervals (recent-onset, medium-term, and long-standing hyperglycemia). RESULTS: Higher FBG over the past 11 years was associated with an increased odds of PaC (p CONCLUSION: Recent-onset hyperglycemia may be an early manifestation of undetected PaC, while long-lasting hyperglycemia may serve as a moderate etiologic factor for PaC.

5 Article Cigarette Smoking and Pancreatic Cancer Survival. 2017

Yuan, Chen / Morales-Oyarvide, Vicente / Babic, Ana / Clish, Clary B / Kraft, Peter / Bao, Ying / Qian, Zhi Rong / Rubinson, Douglas A / Ng, Kimmie / Giovannucci, Edward L / Ogino, Shuji / Stampfer, Meir J / Gaziano, John Michael / Sesso, Howard D / Cochrane, Barbara B / Manson, JoAnn E / Fuchs, Charles S / Wolpin, Brian M. ·Chen Yuan, Vicente Morales-Oyarvide, Ana Babic, Zhi Rong Qian, Douglas A. Rubinson, Kimmie Ng, Shuji Ogino, Charles S. Fuchs, and Brian M. Wolpin, Dana-Farber Cancer Institute and Harvard Medical School · Chen Yuan, Peter Kraft, Edward L. Giovannucci, Shuji Ogino, Meir J. Stampfer, Howard D. Sesso, and JoAnn E. Manson, Harvard School of Public Health · Ying Bao, Edward L. Giovannucci, Shuji Ogino, Meir J. Stampfer, John Michael Gaziano, Howard D. Sesso, JoAnn E. Manson, and Charles S. Fuchs, Brigham and Women's Hospital and Harvard Medical School · John Michael Gaziano, Massachusetts Veterans Epidemiology Research and Information Center, VA Boston Healthcare System, Boston · Clary B. Clish, Broad Institute of Massachusetts Institute of Technology and Harvard University, Cambridge, MA · and Barbara B. Cochrane, University of Washington School of Nursing, Seattle, WA. ·J Clin Oncol · Pubmed #28358654.

ABSTRACT: Purpose Cigarette smoking is associated with increased incidence of pancreatic cancer. However, few studies have prospectively evaluated the association of smoking with patient survival. Patients and Methods We analyzed survival by smoking status among 1,037 patients from two large US prospective cohort studies diagnosed from 1986 to 2013. Among 485 patients from four prospective US cohorts, we also evaluated survival by prediagnostic circulating levels of cotinine, a metabolite of nicotine that is proportional to tobacco smoke exposure. On the basis of prediagnosis cotinine levels, we classified patients as nonsmokers (< 3.1 ng/mL), light smokers (3.1-20.9 ng/mL), or heavy smokers (≥ 21.0 ng/mL). We estimated hazard ratios (HRs) for death by using Cox proportional hazards models, with adjustment for age, sex, race/ethnicity, body mass index, diabetes status, diagnosis year, and cancer stage. Results The multivariable-adjusted HR for death was 1.37 (95% CI, 1.11 to 1.69) comparing current smokers with never smokers ( P = .003). A statistically significant negative trend in survival was observed for increasing pack-years of smoking ( P

6 Article Leucocyte telomere length, genetic variants at the 2017

Bao, Ying / Prescott, Jennifer / Yuan, Chen / Zhang, Mingfeng / Kraft, Peter / Babic, Ana / Morales-Oyarvide, Vicente / Qian, Zhi Rong / Buring, Julie E / Cochrane, Barbara B / Gaziano, J Michael / Giovannucci, Edward L / Manson, JoAnn E / Ng, Kimmie / Ogino, Shuji / Rohan, Thomas E / Sesso, Howard D / Stampfer, Meir J / Fuchs, Charles S / De Vivo, Immaculata / Amundadottir, Laufey T / Wolpin, Brian M. ·Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital, and Harvard Medical School, Boston, Massachusetts, USA. · Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, Massachusetts, USA. · Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts, USA. · Laboratory of Translational Genomics, Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, USA. · Department of Biostatistics, Harvard School of Public Health, Boston, Massachusetts, USA. · Division of Preventive Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, USA. · Department of Ambulatory Care and Prevention, Harvard Medical School, Boston, Massachusetts, USA. · University of Washington School of Nursing, Seattle, Washington, USA. · Massachusetts Veterans Epidemiology Research and Information Center (MAVERIC), VA Boston Healthcare System. · Department of Nutrition, Harvard School of Public Health, Boston, Massachusetts, USA. · Division of MPE Molecular Pathological Epidemiology, Department of Pathology, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, USA. · Department of Epidemiology and Population Health, Albert Einstein College of Medicine, Bronx, New York, USA. · Department of Medicine, Brigham and Women's Hospital, and Harvard Medical School, Boston, Massachusetts, USA. ·Gut · Pubmed #27797938.

ABSTRACT: OBJECTIVE: Telomere shortening occurs as an early event in pancreatic tumorigenesis, and genetic variants at the telomerase reverse transcriptase ( DESIGN: We measured prediagnostic leucocyte telomere length in 386 pancreatic cancer cases and 896 matched controls from five prospective US cohorts. ORs and 95% CIs were calculated using conditional logistic regression. Matching factors included year of birth, cohort (which also matches on sex), smoking status, fasting status and month/year of blood collection. We additionally examined single-nucleotide polymorphisms (SNPs) at the RESULTS: Shorter prediagnostic leucocyte telomere length was associated with higher risk of pancreatic cancer (comparing extreme quintiles of telomere length, OR 1.72; 95% CI 1.07 to 2.78; p CONCLUSIONS: Prediagnostic leucocyte telomere length and genetic variants at the

7 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

8 Article Prediagnostic Plasma 25-Hydroxyvitamin D and Pancreatic Cancer Survival. 2016

Yuan, Chen / Qian, Zhi Rong / Babic, Ana / Morales-Oyarvide, Vicente / Rubinson, Douglas A / Kraft, Peter / Ng, Kimmie / Bao, Ying / Giovannucci, Edward L / Ogino, Shuji / Stampfer, Meir J / Gaziano, John Michael / Sesso, Howard D / Buring, Julie E / Cochrane, Barbara B / Chlebowski, Rowan T / Snetselaar, Linda G / Manson, JoAnn E / Fuchs, Charles S / Wolpin, Brian M. ·Chen Yuan, Zhi Rong Qian, Ana Babic, Vicente Morales-Oyarvide, Douglas A. Rubinson, Kimmie Ng, Shuji Ogino, Charles S. Fuchs, and Brian M. Wolpin, Dana-Farber Cancer Institute and Harvard Medical School · Peter Kraft, Edward L. Giovannucci, Shuji Ogino, Meir J. Stampfer, Howard D. Sesso, Julie E. Buring, and JoAnn E. Manson, Harvard School of Public Health · Ying Bao, Edward L. Giovannucci, Shuji Ogino, Meir J. Stampfer, John Michael Gaziano, Howard D. Sesso, JoAnn E. Manson, and Charles S. Fuchs, Brigham and Women's Hospital and Harvard Medical School · John Michael Gaziano, Massachusetts Veterans Epidemiology Research and Information Center, VA Boston Healthcare System, Boston, MA · Barbara B. Cochrane, University of Washington School of Nursing, Seattle, WA · Rowan T. Chlebowski, Los Angeles Biomedical Research Institute at Harbor-University of California, Los Angeles Medical Center, Torrance, CA · and Linda G. Snetselaar, University of Iowa College of Public Health, Iowa City, IA. ·J Clin Oncol · Pubmed #27325858.

ABSTRACT: PURPOSE: Although vitamin D inhibits pancreatic cancer proliferation in laboratory models, the association of plasma 25-hydroxyvitamin D [25(OH)D] with patient survival is largely unexplored. PATIENTS AND METHODS: We analyzed survival among 493 patients from five prospective US cohorts who were diagnosed with pancreatic cancer from 1984 to 2008. We estimated hazard ratios (HRs) for death by plasma level of 25(OH)D (insufficient, < 20 ng/mL; relative insufficiency, 20 to < 30 ng/mL; sufficient ≥ 30 ng/mL) by using Cox proportional hazards regression models adjusted for age, cohort, race and ethnicity, smoking, diagnosis year, stage, and blood collection month. We also evaluated 30 tagging single-nucleotide polymorphisms in the vitamin D receptor gene, requiring P < .002 (0.05 divided by 30 genotyped variants) for statistical significance. RESULTS: Mean prediagnostic plasma level of 25(OH)D was 24.6 ng/mL, and 165 patients (33%) were vitamin D insufficient. Compared with patients with insufficient levels, multivariable-adjusted HRs for death were 0.79 (95% CI, 0.48 to 1.29) for patients with relative insufficiency and 0.66 (95% CI, 0.49 to 0.90) for patients with sufficient levels (P trend = .01). These results were unchanged after further adjustment for body mass index and history of diabetes (P trend = .02). The association was strongest among patients with blood collected within 5 years of diagnosis, with an HR of 0.58 (95% CI, 0.35 to 0.98) comparing patients with sufficient to patients with insufficient 25(OH)D levels. No single-nucleotide polymorphism at the vitamin D receptor gene met our corrected significance threshold of P < .002; rs7299460 was most strongly associated with survival (HR per minor allele, 0.80; 95% CI, 0.68 to 0.95; P = .01). CONCLUSION: We observed longer overall survival in patients with pancreatic cancer who had sufficient prediagnostic plasma levels of 25(OH)D.

9 Article Association of Physical Activity by Type and Intensity With Digestive System Cancer Risk. 2016

Keum, NaNa / Bao, Ying / Smith-Warner, Stephanie A / Orav, John / Wu, Kana / Fuchs, Charles S / Giovannucci, Edward L. ·Department of Nutrition, Harvard T. H. Chan School of Public Health, Boston, Massachusetts. · Channing Division of Network Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts. · Department of Nutrition, Harvard T. H. Chan School of Public Health, Boston, Massachusetts3Department of Epidemiology, Harvard T. H. Chan School of Public Health, Boston, Massachusetts. · Department of Biostatistics, Harvard T. H. Chan School of Public Health, Boston, Massachusetts5Department of Medicine, Harvard Medical School, Boston, Massachusetts. · Department of Medicine, Harvard Medical School, Boston, Massachusetts6Department of Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts. · Department of Nutrition, Harvard T. H. Chan School of Public Health, Boston, Massachusetts2Channing Division of Network Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts3Department of Epidemiology, Harvard T. H. Chan School of Public Health, Boston, Massachusetts5Department of Medicine, Harvard Medical School, Boston, Massachusetts. ·JAMA Oncol · Pubmed #27196375.

ABSTRACT: IMPORTANCE: Accumulating evidence indicates that common carcinogenic pathways may underlie digestive system cancers. Physical activity may influence these pathways. Yet, to our knowledge, no previous study has evaluated the role of physical activity in overall digestive system cancer risk. OBJECTIVE: To examine the association between physical activity and digestive system cancer risk, accounting for amount, type (aerobic vs resistance), and intensity of physical activity. DESIGN, SETTING, AND PARTICIPANTS: A prospective cohort study followed 43 479 men from the Health Professionals Follow-up Study from 1986 to 2012. At enrollment, the eligible participants were 40 years or older, were free of cancer, and reported physical activity. Follow-up rates exceeded 90% in each 2-year cycle. EXPOSURES: The amount of total physical activity expressed in metabolic equivalent of task (MET)-hours/week. MAIN OUTCOMES AND MEASURES: Incident cancer of the digestive system encompassing the digestive tract (mouth, throat, esophagus, stomach, small intestine, and colorectum) and digestive accessory organs (pancreas, gallbladder, and liver). RESULTS: Over 686 924 person-years, we documented 1370 incident digestive system cancers. Higher levels of physical activity were associated with lower digestive system cancer risk (hazard ratio [HR], 0.74 for ≥63.0 vs ≤8.9 MET-hours/week; 95% CI, 0.59-0.93; P value for trend = .003). The inverse association was more evident with digestive tract cancers (HR, 0.66 for ≥63.0 vs ≤8.9 MET-hours/week; 95% CI, 0.51-0.87) than with digestive accessary organ cancers. Aerobic exercise was particularly beneficial against digestive system cancers, with the optimal benefit observed at approximately 30 MET-hours/week (HR, 0.68; 95% CI, 0.56-0.83; P value for nonlinearity = .02). Moreover, as long as the same level of MET-hour score was achieved from aerobic exercise, the magnitude of risk reduction was similar regardless of intensity of aerobic exercise. CONCLUSIONS AND RELEVANCE: Physical activity, as indicated by MET-hours/week, was inversely associated with the risk of digestive system cancers, particularly digestive tract cancers, in men. The optimal benefit was observed through aerobic exercise of any intensity at the equivalent of energy expenditure of approximately 10 hours/week of walking at average pace. Future studies are warranted to confirm our findings and to translate them into clinical and public health recommendation.

10 Article Circulating Metabolites and Survival Among Patients With Pancreatic Cancer. 2016

Yuan, Chen / Clish, Clary B / Wu, Chen / Mayers, Jared R / Kraft, Peter / Townsend, Mary K / Zhang, Mingfeng / Tworoger, Shelley S / Bao, Ying / Qian, Zhi Rong / Rubinson, Douglas A / Ng, Kimmie / Giovannucci, Edward L / Ogino, Shuji / Stampfer, Meir J / Gaziano, John Michael / Ma, Jing / Sesso, Howard D / Anderson, Garnet L / Cochrane, Barbara B / Manson, JoAnn E / Torrence, Margaret E / Kimmelman, Alec C / Amundadottir, Laufey T / Vander Heiden, Matthew G / Fuchs, Charles S / Wolpin, Brian M. ·Department of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, MA (CY, ZRQ, DAR, KN, SO, MGVH, CSF, BMW) · Broad Institute of MIT and Harvard University, Cambridge, MA (CBC, MGVH) · Department of Etiology and Carcinogenesis, Cancer Institute and Hospital, Chinese Academy of Medical Science and Peking Union Medical College, Beijing, China (CW) · Koch Institute for Integrative Cancer Research and Department of Biology, Massachusetts Institute of Technology, Cambridge, MA (JRM, MET, MGVH) · Department of Epidemiology (PK, SST, ELG, SO, MJS, JM, HDS, JEM), Department of Biostatistics (PK), and Department of Nutrition (ELG, MJS), Harvard School of Public Health, Boston, MA · Department of Pathology (SO), and Channing Division of Network Medicine (MKT, SST, YB, ELG, MJS, JM, JEM, CSF) and Division of Preventive Medicine (JMG, HDS, JEM), Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA · Laboratory of Translational Genomics, Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, MD (MZ, LTA) · Massachusetts Veterans Epidemiology Research and Information Center (MAVERIC), VA Boston Healthcare System, Boston, MA (JMG) · Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, WA (GLA) · University of Washington School of Nursing, Seattle, WA (BBC) · Division of Genomic Stability and DNA repair, Department of Radiation Oncology, Dana-Farber Cancer Institute, Boston, MA (ACK). ·J Natl Cancer Inst · Pubmed #26755275.

ABSTRACT: BACKGROUND: Pancreatic tumors cause changes in whole-body metabolism, but whether prediagnostic circulating metabolites predict survival is unknown. METHODS: We measured 82 metabolites by liquid chromatography-mass spectrometry in prediagnostic plasma from 484 pancreatic cancer case patients enrolled in four prospective cohort studies. Association of metabolites with survival was evaluated using Cox proportional hazards models adjusted for age, cohort, race/ethnicity, cancer stage, fasting time, and diagnosis year. After multiple-hypothesis testing correction, a P value of .0006 or less (.05/82) was considered statistically significant. Based on the results, we evaluated 33 tagging single-nucleotide polymorphisms (SNPs) in the ACO1 gene, requiring a P value of less than .002 (.05/33) for statistical significance. All statistical tests were two-sided. RESULTS: Two metabolites in the tricarboxylic acid (TCA) cycle--isocitrate and aconitate--were statistically significantly associated with survival. Participants in the highest vs lowest quintile had hazard ratios (HRs) for death of 1.89 (95% confidence interval [CI] = 1.06 to 3.35, Ptrend < .001) for isocitrate and 2.54 (95% CI = 1.42 to 4.54, Ptrend < .001) for aconitate. Isocitrate is interconverted with citrate via the intermediate aconitate in a reaction catalyzed by the enzyme aconitase 1 (ACO1). Therefore, we investigated the citrate to aconitate plus isocitrate ratio and SNPs in the ACO1 gene. The ratio was strongly associated with survival (P trend < .001) as was the SNP rs7874815 in the ACO1 gene (hazard ratio for death per minor allele = 1.37, 95% CI = 1.16 to 1.61, P < .001). Patients had an approximately three-fold hazard for death when possessing one or more minor alleles at rs7874851 and high aconitate or isocitrate. CONCLUSIONS: Prediagnostic circulating levels of TCA cycle intermediates and inherited ACO1 genotypes were associated with survival among patients with pancreatic cancer.

11 Article Survival among patients with pancreatic cancer and long-standing or recent-onset diabetes mellitus. 2015

Yuan, Chen / Rubinson, Douglas A / Qian, Zhi Rong / Wu, Chen / Kraft, Peter / Bao, Ying / Ogino, Shuji / Ng, Kimmie / Clancy, Thomas E / Swanson, Richard S / Gorman, Megan J / Brais, Lauren K / Li, Tingting / Stampfer, Meir J / Hu, Frank B / Giovannucci, Edward L / Kulke, Matthew H / Fuchs, Charles S / Wolpin, Brian M. ·Chen Yuan, Douglas A. Rubinson, Zhi Rong Qian, Shuji Ogino, Kimmie Ng, Megan J. Gorman, Lauren K. Brais, Tingting Li, Matthew H. Kulke, Charles S. Fuchs, and Brian M. Wolpin, Dana-Farber Cancer Institute · Chen Wu, Peter Kraft, Shuji Ogino, Meir J. Stampfer, Frank B. Hu, and Edward L. Giovannucci, Harvard School of Public Health · and Ying Bao, Shuji Ogino, Kimmie Ng, Thomas E. Clancy, Richard S. Swanson, Meir J. Stampfer, Frank B. Hu, Edward L. Giovannucci, Matthew H. Kulke, Charles S. Fuchs, and Brian M. Wolpin, Brigham and Women's Hospital and Harvard Medical School, Boston, MA. ·J Clin Oncol · Pubmed #25403204.

ABSTRACT: PURPOSE: Long-standing diabetes is a risk factor for pancreatic cancer, and recent-onset diabetes in the several years before diagnosis is a consequence of subclinical pancreatic malignancy. However, the impact of diabetes on survival is largely unknown. PATIENTS AND METHODS: We analyzed survival by diabetes status among 1,006 patients diagnosed from 1986 to 2010 from two prospective cohort studies: the Nurses' Health Study (NHS) and Health Professionals Follow-Up Study (HPFS). We validated our results among 386 patients diagnosed from 2004 to 2013 from a clinic-based case series at Dana-Farber Cancer Institute (DFCI). We estimated hazard ratios (HRs) for death using Cox proportional hazards models, with adjustment for age, sex, race/ethnicity, smoking, diagnosis year, and cancer stage. RESULTS: In NHS and HPFS, HR for death was 1.40 (95% CI, 1.15 to 1.69) for patients with long-term diabetes (> 4 years) compared with those without diabetes (P < .001), with median survival times of 3 months for long-term diabetics and 5 months for nondiabetics. Adjustment for a propensity score to reduce confounding by comorbidities did not change the results. Among DFCI patient cases, HR for death was 1.53 (95% CI, 1.07 to 2.20) for those with long-term diabetes compared with those without diabetes (P = .02), with median survival times of 9 months for long-term diabetics and 13 months for nondiabetics. Compared with nondiabetics, survival times were shorter for long-term diabetics who used oral hypoglycemics or insulin. We observed no statistically significant association of recent-onset diabetes (< 4 years) with survival. CONCLUSION: Long-standing diabetes was associated with statistically significantly decreased survival among patients with pancreatic cancer enrolled onto three longitudinal studies.

12 Article Hepatic arterial infusion chemotherapy reduced hepatic metastases from pancreatic cancer after pancreatectomy. 2014

Zheng, Yin Yuan / Tang, Cheng Wu / Xu, Yong Qiang / Feng, Wen Ming / Bao, Ying / Fei, Mao Yun. · ·Hepatogastroenterology · Pubmed #25436319.

ABSTRACT: BACKGROUND/AIMS: This study aims to investigate the safety and efficacy of hepatic arterial infusion chemotherapy (HAIC) on liver metastases from pancreatic cancer after pancreatectomy. METHODOLOGY: We randomly assigned 106 patients with pancreatic cancer after pancreatectomy between 2005 and 2010 to receive 2 cycles of HAIC plus 4 cycles of systemic chemotherapy (Combined Therapy) or 6 cycles of systemic chemotherapy alone (Monotherapy). Both the HAIC and systemic chemotherapy regimen consisted of a 5-hour infusion of 5-fluorouracil 1000 mg/m2 on day 1 followed by gemcitabine 800 mg/m2 as an over 30-min infusion on day 1 and day 8. The treatment was started on an average of 21.2 days after surgery and repeated every 4 weeks. The disease-free survival, overall survival and liver metastases-free survival were compared. RESULTS: There was no significant difference in adverse effects between two groups. Significant differences were found in 3-year overall survival (Combined Therapy, 23.08 %; Monotherapy, 14.81%; P=0.0473) and liver metastases-free survival (Combined Therapy, 80.77%; Monotherapy, 55.56%; P=0.0014). CONCLUSIONS: HAIC effectively and safely prevents liver metastases and improves the prognosis of patients with pancreatic cancer after pancreatectomy.

13 Article Elevation of circulating branched-chain amino acids is an early event in human pancreatic adenocarcinoma development. 2014

Mayers, Jared R / Wu, Chen / Clish, Clary B / Kraft, Peter / Torrence, Margaret E / Fiske, Brian P / Yuan, Chen / Bao, Ying / Townsend, Mary K / Tworoger, Shelley S / Davidson, Shawn M / Papagiannakopoulos, Thales / Yang, Annan / Dayton, Talya L / Ogino, Shuji / Stampfer, Meir J / Giovannucci, Edward L / Qian, Zhi Rong / Rubinson, Douglas A / Ma, Jing / Sesso, Howard D / Gaziano, John Michael / Cochrane, Barbara B / Liu, Simin / Wactawski-Wende, Jean / Manson, JoAnn E / Pollak, Michael N / Kimmelman, Alec C / Souza, Amanda / Pierce, Kerry / Wang, Thomas J / Gerszten, Robert E / Fuchs, Charles S / Vander Heiden, Matthew G / Wolpin, Brian M. ·Koch Institute for Integrative Cancer Research and Department of Biology, Massachusetts Institute of Technology, Cambridge, MA. · Department of Etiology and Carcinogenesis, Cancer Institute and Hospital, Chinese Academy of Medical Science and Peking Union Medical College, Beijing, China. · Department of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, MA. · Department of Epidemiology, Harvard School of Public Health, Boston, MA. · Broad Institute of MIT and Harvard University, Cambridge, MA. · Department of Biostatistics, Harvard School of Public Health, Boston, MA. · Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA. · Division of Genomic Stability and DNA repair, Department of Radiation Oncology, Dana- Farber Cancer Institute, Boston, MA 02215. · Department of Pathology, Brigham and Women's Hospital and Harvard Medical School, Boston, MA. · Department of Nutrition, Harvard School of Public Health, Boston, MA. · Division of Preventive Medicine, Department of Medicine, Brigham and Women's Hospital, and Harvard Medical School, Boston, MA. · Massachusetts Veterans Epidemiology Research and Information Center (MAVERIC), VA Boston Healthcare System. · University of Washington School of Nursing, Seattle, WA. · Departments of Epidemiology and Medicine, Brown University, Providence, RI. · Department of Social and Preventive Medicine, University at Buffalo, SUNY, Buffalo, NY. · Departments of Oncology and Medicine, McGill University, Montreal, QC, Canada. · Division of Cardiovascular Medicine, Vanderbilt University, Nashville, TN. · Cardiology Division, Massachusetts General Hospital, and Harvard Medical School, Boston, MA. · Department of Medicine, Brigham and Women's Hospital, and Harvard Medical School, Boston, MA. ·Nat Med · Pubmed #25261994.

ABSTRACT: Most patients with pancreatic ductal adenocarcinoma (PDAC) are diagnosed with advanced disease and survive less than 12 months. PDAC has been linked with obesity and glucose intolerance, but whether changes in circulating metabolites are associated with early cancer progression is unknown. To better understand metabolic derangements associated with early disease, we profiled metabolites in prediagnostic plasma from individuals with pancreatic cancer (cases) and matched controls from four prospective cohort studies. We find that elevated plasma levels of branched-chain amino acids (BCAAs) are associated with a greater than twofold increased risk of future pancreatic cancer diagnosis. This elevated risk was independent of known predisposing factors, with the strongest association observed among subjects with samples collected 2 to 5 years before diagnosis, when occult disease is probably present. We show that plasma BCAAs are also elevated in mice with early-stage pancreatic cancers driven by mutant Kras expression but not in mice with Kras-driven tumors in other tissues, and that breakdown of tissue protein accounts for the increase in plasma BCAAs that accompanies early-stage disease. Together, these findings suggest that increased whole-body protein breakdown is an early event in development of PDAC.

14 Article Spleen-preserving distal pancreatectomy or distal pancreatectomy with splenectomy?: Perioperative and patient-reported outcome analysis. 2014

Tang, Cheng Wu / Feng, Wen Ming / Bao, Ying / Fei, Mao Yun / Tao, Yu Long. ·Department of Hepatobiliary Surgery, First People's Hospital affiliated to Huzhou University Medical College, Huzhou, Zhejiang Province, China. ·J Clin Gastroenterol · Pubmed #24231937.

ABSTRACT: GOALS: We designed this study to evaluate the efficacy of spleen salvage during distal pancreatectomy for patients with benign and borderline malignant tumors. BACKGROUND: Despite the emphasis on its role, the spleen has commonly been removed in distal pancreatectomy. STUDY: From January 2005 to July 2009, 82 patients underwent distal pancreatectomy with splenectomy (DPS) and 78 patients underwent spleen-preserving distal pancreatectomy (SPDP). Medical records were retrospectively reviewed. RESULTS: There were no significant differences in demographics, final diagnoses, estimated blood loss, intraoperative transfusion, and operative time between the 2 groups. More perioperative complications occurred in the DPS group than in the SPDP group (P=0.0344). Consequently, postoperative hospital stay was significantly shorter in the SPDP group than in the DPS group (P=0.0273). In the follow-up survey, episodes of common cold or flu were apparently more frequent in the DPS group (P=0.047). More patients in the DPS group felt fatigue (P=0.0481) and poor health condition (P=0.0371). Less newly developed (P=0.0193) and aggravated diabetes mellitus (P=0.0361) were also observed in the SPDP group. Platelet counts on postoperative day (POD) 5, hemoglobin on POD 3, WBC counts, and CRP level on POD 2 were significantly higher in the DPS group than in the SPDP group and these differences continued to be significant for months after surgery. CONCLUSIONS: In addition to frequent higher grade complications, prolonged hospital stays, and severe hematological abnormalities, DPS seemed to result in poor health condition based on the follow-up survey. Even an effort to preserve an adult spleen in distal pancreatectomy is worthwhile.

15 Article Prediagnostic body mass index and pancreatic cancer survival. 2013

Yuan, Chen / Bao, Ying / Wu, Chen / Kraft, Peter / Ogino, Shuji / Ng, Kimmie / Qian, Zhi Rong / Rubinson, Douglas A / Stampfer, Meir J / Giovannucci, Edward L / Wolpin, Brian M. ·Chen Yuan, Shuji Ogino, Kimmie Ng, Zhi Rong Qian, Douglas A. Rubinson, and Brian M. Wolpin, Dana-Farber Cancer Institute · Ying Bao, Shuji Ogino, Kimmie Ng, Meir J. Stampfer, Edward L. Giovannucci, and Brian M. Wolpin, Brigham and Women's Hospital, Harvard Medical School · and Chen Wu, Peter Kraft, Shuji Ogino, Meir J. Stampfer, and Edward L. Giovannucci, Harvard School of Public Health, Boston, MA. ·J Clin Oncol · Pubmed #24145341.

ABSTRACT: PURPOSE: Although obesity is associated with increased incidence of pancreatic cancer, studies have not prospectively evaluated prediagnostic body mass index (BMI) and survival. PATIENTS AND METHODS: We analyzed survival by prediagnostic BMI assessed in 1986 among 902 patients from two large prospective cohorts diagnosed from 1988 to 2010. We estimated hazard ratios (HRs) for death using Cox proportional hazards models, with adjustment for age, sex, race/ethnicity, smoking, diagnosis year, and stage. We evaluated the temporal association of BMI with survival by grouping reported BMI by 2-year lag-time intervals before diagnosis. RESULTS: The multivariable-adjusted HR for death was 1.53 (95% CI, 1.11 to 2.09) comparing patients with BMI ≥ 35 kg/m(2) with those with BMI < 25 kg/m(2) (P trend = .001), which was similar after adjustment for stage. The association of BMI with survival was stronger with longer lag times between reported BMI and cancer diagnosis. Among patients with BMI collected 18 to 20 years before diagnosis, HR for death was 2.31 (95% CI, 1.48 to 3.61; P trend < .001), comparing obese with healthy-weight patients. No statistically significant differences were seen by cohort, smoking status, or stage, although the association was stronger among never-smokers (HR, 1.61; 95% CI, 1.01 to 2.57; P trend = .002) than ever-smokers (HR, 1.36; 95% CI, 0.86 to 2.15; P trend = .63), comparing BMI ≥ 35 kg/m(2) with BMI < 25 kg/m(2). Higher prediagnostic BMI was associated with more advanced stage at diagnosis, with 72.5% of obese patients presenting with metastatic disease versus 59.4% of healthy-weight patients (P = .02). CONCLUSION: Higher prediagnostic BMI was associated with statistically significantly decreased survival among patients with pancreatic cancer from two large prospective cohorts.

16 Article Hematological benefits after spleen-preserving distal pancreatectomy: perioperative and long-term outcome analysis. 2013

Xu, Ju Ling / Tang, Cheng Wu / Feng, Wen Ming / Bao, Ying. · ·Hepatogastroenterology · Pubmed #24088313.

ABSTRACT: BACKGROUND/AIMS: Despite the emphasis on its role, the spleen has commonly been removed in distal pancreatectomy. We designed this study to evaluate the efficacy of spleen salvage during distal pancreatectomy for patients with benign and borderline malignant tumors. METHODOLOGY: From January 2005 to July 2009, 82 patients underwent distal pancreatectomy with splenectomy (DPS) and 78 patients underwent spleen-preserving distal pancreatectomy (SPDP). Medical records were retrospectively reviewed. RESULTS: The demographics and final diagnoses were similar between the two groups. There were no significant differences in estimated blood loss, intraoperative transfusion and operative time between the two groups. More perioperative complications occurred in DPS group than in the SPDP group (p = 0.0344). Consequently, postoperative hospital stay was significantly shorter in SPDP group than in DPS group (p = 0.0273). Platelet counts on postoperative day (POD) 5, hemoglobin on POD 3, WBC counts and CRP level on POD 2 were significantly higher in the DPS group than in the SPDP group and these differences continued to be significant for months after surgery. CONCLUSIONS: In addition to frequent higher-grade complications, prolonged hospital stays, DPS appeared to result in severer hematological abnormalities. Even an effort to preserve adult spleen in distal pancreatectomy is worthwhile.

17 Article Spleen-preserving distal pancreatectomy: perioperative and long-term outcome analysis. 2013

Feng, Wen Ming / Tang, Cheng Wu / Bao, Ying / Fei, Mao Yun / Tao, Yu Long. · ·Hepatogastroenterology · Pubmed #23933832.

ABSTRACT: BACKGROUND/AIMS: Despite the emphasis on its role, the spleen has commonly been removed in distal pancreatectomy. We aimed to evaluate the efficacy of spleen salvage during distal pancreatectomy for patients with benign and borderline malignant tumors. METHODOLOGY: 82 patients underwent distal pancreatectomy with splenectomy (DPS) and 78 patients underwent spleen-preserving distal pancreatectomy (SPDP). Medical records were retrospectively reviewed. RESULTS: There were no significant differences in demographics, final diagnoses estimated blood loss, intraoperative transfusion and operative time between the two groups. More perioperative complications occurred in DPS group than in the SPDP group (p = 0.0344). Consequently, postoperative hospital stay was significantly shorter in SPDP group than in DPS group (p = 0.0273). On the follow-up survey, episodes of common cold or flu were apparently more frequent in the DPS group (p = 0.047). More patients in the DPS group felt fatigue (p = 0.0481) and poorer health condition (p = 0.0371). Less newly developed (p = 0.0193) and aggravated diabetes mellitus (p = 0.0361) were also observed in SPDP group. CONCLUSIONS: In addition to frequent higher-grade complications, and prolonged hospital stays, DPS appeared to result in poorer health condition based on follow-up survey. Even an effort to preserve adult spleen in distal pancreatectomy is worthwhile.

18 Article Hyperglycemia, insulin resistance, impaired pancreatic β-cell function, and risk of pancreatic cancer. 2013

Wolpin, Brian M / Bao, Ying / Qian, Zhi Rong / Wu, Chen / Kraft, Peter / Ogino, Shuji / Stampfer, Meir J / Sato, Kaori / Ma, Jing / Buring, Julie E / Sesso, Howard D / Lee, I-Min / Gaziano, John Michael / McTiernan, Anne / Phillips, Lawrence S / Cochrane, Barbara B / Pollak, Michael N / Manson, JoAnn E / Giovannucci, Edward L / Fuchs, Charles S. ·Department of Medicine, Brigham and Women's Hospital, and Harvard Medical School, Boston, MA 02215, USA. bwolpin@partners.org ·J Natl Cancer Inst · Pubmed #23847240.

ABSTRACT: BACKGROUND: Obesity and diabetes mellitus are associated with an increased risk of pancreatic cancer. These associations may be secondary to consequences of peripheral insulin resistance, pancreatic β-cell dysfunction, or hyperglycemia itself. Hemoglobin A1c (HbA1c) is a measure of hyperglycemia, whereas plasma insulin and proinsulin are markers of peripheral insulin resistance, and the proinsulin to insulin ratio marks pancreatic β-cell dysfunction. METHODS: This was a prospective, nested case-control study of 449 case patients and 982 control subjects with prediagnostic blood samples and no diabetes history from five prospective US cohorts followed through 2008. Two or three control subjects were matched to each case patient by year of birth, cohort, smoking, and fasting status. Pancreatic cancer risk was assessed by prediagnostic HbA1c, insulin, proinsulin, and proinsulin to insulin ratio with multivariable-adjusted logistic regression. All P values were two-sided. RESULTS: The highest vs lowest quintiles of HbA1c, insulin, and proinsulin were associated with with an increased risk for pancreatic cancer (odds ratio [OR] = 1.79; 95% confidence interval [CI] = 1.17 to 2.72, P trend = .04 for HbA1c; OR = 1.57; 95% CI = 1.08 to 2.30; Ptrend = .002 for insulin; and OR = 2.22; 95% CI = 1.50 to 3.29; P trend < .001 for proinsulin). Proinsulin to insulin ratio was not associated with pancreatic cancer risk. Results were similar across studies (all P heterogeneity > .29). In cancers developing 10 or more years after blood collection, the associations with insulin and proinsulin became stronger (highest vs lowest quintile, OR = 2.77; 95% CI = 1.28 to 5.99 for insulin and OR = 3.60; 95% CI = 1.68 to 7.72 for proinsulin). In mutually adjusted models including HbA1c, insulin, and proinsulin, only proinsulin remained statistically significant ( highest vs lowest quintile, OR = 2.55; 95% CI = 1.54 to 4.21; Ptrend < .001). CONCLUSIONS: Among participants from five large prospective cohorts, circulating markers of peripheral insulin resistance, rather than hyperglycemia or pancreatic β-cell dysfunction, were independently associated with pancreatic cancer risk.

19 Article Inflammatory plasma markers and pancreatic cancer risk: a prospective study of five U.S. cohorts. 2013

Bao, Ying / Giovannucci, Edward L / Kraft, Peter / Qian, Zhi Rong / Wu, Chen / Ogino, Shuji / Gaziano, J Michael / Stampfer, Meir J / Ma, Jing / Buring, Julie E / Sesso, Howard D / Lee, I-Min / Rifai, Nader / Pollak, Michael N / Jiao, Li / Lessin, Lawrence / Cochrane, Barbara B / Manson, Joann E / Fuchs, Charles S / Wolpin, Brian M. ·Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, 181 Longwood Avenue, Boston, MA 02115, USA. ying.bao@channing.harvard.edu ·Cancer Epidemiol Biomarkers Prev · Pubmed #23462920.

ABSTRACT: Chronic inflammation may play a role in the development of pancreatic cancer. However, few prospective studies have examined the association between plasma inflammatory markers and pancreatic cancer risk. Therefore, we investigated the association of prediagnostic circulating C-reactive protein (CRP), interleukin-6 (IL-6), and TNF-α receptor II (TNF-αR2) with subsequent pancreatic cancer risk in a prospective, nested case-control study of 470 cases and 1,094 controls from Health Professionals Follow-up Study, Nurses' Health Study, Physicians' Health Study, Women's Health Initiative, and Women's Health Study. The median follow-up time of cases was 7.2 years (range 1-26 years). No association was observed between plasma CRP, IL-6, and TNF-αR2 and the risk of pancreatic cancer. Comparing extreme quintiles, the multivariate ORs were 1.10 [95% confidence interval (CI), 0.74-1.63; Ptrend = 0.81] for CRP, 1.19 (95% CI, 0.81-1.76; Ptrend = 0.08) for IL-6, and 0.88 (95% CI, 0.58-1.33; Ptrend = 0.57) for TNF-αR2. In conclusion, prediagnostic levels of circulating CRP, IL-6, and TNF-αR2 were not associated with the risk of pancreatic cancer, suggesting that systemic inflammation as measured by circulating inflammatory factors is unlikely to play a major role in the development of pancreatic cancer.

20 Article A prospective study of plasma adiponectin and pancreatic cancer risk in five US cohorts. 2013

Bao, Ying / Giovannucci, Edward L / Kraft, Peter / Stampfer, Meir J / Ogino, Shuji / Ma, Jing / Buring, Julie E / Sesso, Howard D / Lee, I-Min / Gaziano, John Michael / Rifai, Nader / Pollak, Michael N / Cochrane, Barbara B / Kaklamani, Virginia / Lin, Jennifer H / Manson, Joann E / Fuchs, Charles S / Wolpin, Brian M. ·Channing Laboratory, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, 181 Longwood Ave, Boston, MA 02115, USA. ying.bao@channing.harvard.edu ·J Natl Cancer Inst · Pubmed #23243202.

ABSTRACT: BACKGROUND: The adipocyte-secreted hormone adiponectin has insulin-sensitizing and anti-inflammatory properties. Although development of pancreatic cancer is associated with states of insulin resistance and chronic inflammation, the mechanistic basis of the associations is poorly understood. METHODS: To determine whether prediagnostic plasma levels of adiponectin are associated with risk of pancreatic cancer, we conducted a nested case-control study of 468 pancreatic cancer case subjects and 1080 matched control subjects from five prospective US cohorts: Health Professionals Follow-up Study, Nurses' Health Study, Physicians' Health Study, Women's Health Initiative, and Women's Health Study. Control subjects were matched to case subjects by prospective cohort, year of birth, smoking status, fasting status, and month of blood draw. All samples for plasma adiponectin were handled identically in a single batch. Odds ratios were calculated with conditional logistic regression, and linearity of the association between adiponectin and pancreatic cancer was modeled with restricted cubic spline regression. All statistical tests were two-sided. RESULTS: Median plasma adiponectin was lower in case subjects versus control subjects (6.2 vs 6.8 µg/mL, P = .009). Plasma adiponectin was inversely associated with pancreatic cancer risk, which was consistent across the five prospective cohorts (P (heterogeneity) = .49) and independent of other markers of insulin resistance (eg, diabetes, body mass index, physical activity, plasma C-peptide). Compared with the lowest quintile of adiponectin, individuals in quintiles 2 to 5 had multivariable odds ratios ([ORs] 95% confidence intervals [CIs]) of OR = 0.61 (95% CI = 0.43 to 0.86), OR = 0.58 (95% CI = 0.41 to 0.84), OR = 0.59 (95% CI = 0.40 to 0.87), and OR = 0.66 (95% CI = 0.44 to 0.97), respectively (P (trend) = .04). Restricted cubic spline regression confirmed a nonlinear association (P (nonlinearity) < .01). The association was not modified by sex, smoking, body mass index, physical activity, or C-peptide (all P (interaction) > .10). CONCLUSIONS: In this pooled analysis, low prediagnostic levels of circulating adiponectin were associated with an elevated risk of pancreatic cancer.

21 Article Diabetes and risk of pancreatic cancer: a pooled analysis from the pancreatic cancer cohort consortium. 2013

Elena, Joanne W / Steplowski, Emily / Yu, Kai / Hartge, Patricia / Tobias, Geoffrey S / Brotzman, Michelle J / Chanock, Stephen J / Stolzenberg-Solomon, Rachael Z / Arslan, Alan A / Bueno-de-Mesquita, H Bas / Helzlsouer, Kathy / Jacobs, Eric J / LaCroix, Andrea / Petersen, Gloria / Zheng, Wei / Albanes, Demetrius / Allen, Naomi E / Amundadottir, Laufey / Bao, Ying / Boeing, Heiner / Boutron-Ruault, Marie-Christine / Buring, Julie E / Gaziano, J Michael / Giovannucci, Edward L / Duell, Eric J / Hallmans, Göran / Howard, Barbara V / Hunter, David J / Hutchinson, Amy / Jacobs, Kevin B / Kooperberg, Charles / Kraft, Peter / Mendelsohn, Julie B / Michaud, Dominique S / Palli, Domenico / Phillips, Lawrence S / Overvad, Kim / Patel, Alpa V / Sansbury, Leah / Shu, Xiao-Ou / Simon, Michael S / Slimani, Nadia / Trichopoulos, Dimitrios / Visvanathan, Kala / Virtamo, Jarmo / Wolpin, Brian M / Zeleniuch-Jacquotte, Anne / Fuchs, Charles S / Hoover, Robert N / Gross, Myron. ·Division of Cancer Control and Population Science, National Cancer Institute, National Institutes of Health, Department of Health and Human Services, Bethesda, MD 20892, USA. elenajw@mail.nih.gov ·Cancer Causes Control · Pubmed #23112111.

ABSTRACT: PURPOSE: Diabetes is a suspected risk factor for pancreatic cancer, but questions remain about whether it is a risk factor or a result of the disease. This study prospectively examined the association between diabetes and the risk of pancreatic adenocarcinoma in pooled data from the NCI pancreatic cancer cohort consortium (PanScan). METHODS: The pooled data included 1,621 pancreatic adenocarcinoma cases and 1,719 matched controls from twelve cohorts using a nested case-control study design. Subjects who were diagnosed with diabetes near the time (<2 years) of pancreatic cancer diagnosis were excluded from all analyses. All analyses were adjusted for age, race, gender, study, alcohol use, smoking, BMI, and family history of pancreatic cancer. RESULTS: Self-reported diabetes was associated with a forty percent increased risk of pancreatic cancer (OR = 1.40, 95 % CI: 1.07, 1.84). The association differed by duration of diabetes; risk was highest for those with a duration of 2-8 years (OR = 1.79, 95 % CI: 1.25, 2.55); there was no association for those with 9+ years of diabetes (OR = 1.02, 95 % CI: 0.68, 1.52). CONCLUSIONS: These findings provide support for a relationship between diabetes and pancreatic cancer risk. The absence of association in those with the longest duration of diabetes may reflect hypoinsulinemia and warrants further investigation.

22 Article Plasma 25-hydroxyvitamin D and risk of pancreatic cancer. 2012

Wolpin, Brian M / Ng, Kimmie / Bao, Ying / Kraft, Peter / Stampfer, Meir J / Michaud, Dominique S / Ma, Jing / Buring, Julie E / Sesso, Howard D / Lee, I-Min / Rifai, Nader / Cochrane, Barbara B / Wactawski-Wende, Jean / Chlebowski, Rowan T / Willett, Walter C / Manson, JoAnn E / Giovannucci, Edward L / Fuchs, Charles S. ·Department of Medical Oncology, Dana-Farber Cancer Institute, 450 Brookline Avenue, Boston, MA 02215, USA. bwolpin@partners.org ·Cancer Epidemiol Biomarkers Prev · Pubmed #22086883.

ABSTRACT: BACKGROUND: Laboratory studies suggest that vitamin D may inhibit pancreatic cancer cell growth. However, epidemiologic studies of vitamin D and pancreatic cancer risk have been conflicting. METHODS: To determine whether prediagnostic levels of plasma 25-hydroxyvitamin D (25[OH]D; IDS Inc.; enzyme immunoassay) were associated with risk of pancreatic cancer, we conducted a pooled analysis of nested case-control studies with 451 cases and 1,167 controls from five cohorts through 2008. Median follow-up among controls was 14.1 years in Health Professionals Follow-Up Study (HPFS), 18.3 years in Nurses' Health Study (NHS), 25.3 years in Physicians' Health Study (PHS), 12.2 years in Women's Health Initiative-Observational Study (WHI), and 14.4 years in Women's Health Study (WHS). Logistic regression was used to compare the odds of pancreatic cancer by plasma level of 25(OH)D. RESULTS: Mean plasma 25(OH)D was lower in cases versus controls (61.3 vs. 64.5 nmol/L, P = 0.005). In logistic regression models, plasma 25(OH)D was inversely associated with odds of pancreatic cancer. Participants in quintiles two through five had multivariable-adjusted ORs (95% confidence intervals) of 0.79 (0.56-1.10), 0.75 (0.53-1.06), 0.68 (0.48-0.97), and 0.67 (0.46-0.97; P(trend) = 0.03), respectively, compared with the bottom quintile. Compared with those with insufficient levels [25[OH]D, <50 nmol/L], ORs were 0.75 (0.58-0.98) for subjects with relative insufficiency [25[OH]D, 50 to <75 nmol/L] and 0.71 (0.52-0.97) for those with sufficient levels [25[OH]D, ≥ 75 nmol/L]. No increased risk was noted in subjects with 25(OH)D ≥100 nmol/L, as suggested in a prior study. In subgroup analyses, ORs for the top versus bottom quartile of 25(OH)D were 0.72 (0.48-1.08) for women, 0.73 (0.40-1.31) for men, and 0.73 (0.51-1.03) for Whites. CONCLUSIONS: Among participants in five large prospective cohorts, higher plasma levels of 25(OH)D were associated with a lower risk for pancreatic cancer. IMPACT: Low circulating 25(OH)D may predispose individuals to the development of pancreatic cancer.

23 Article Dietary insulin load, dietary insulin index, and risk of pancreatic cancer. 2011

Bao, Ying / Nimptsch, Katharina / Wolpin, Brian M / Michaud, Dominique S / Brand-Miller, Jennie C / Willett, Walter C / Giovannucci, Edward / Fuchs, Charles S. ·Channing Laboratory, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA. ying.bao@channing.harvard.edu ·Am J Clin Nutr · Pubmed #21775564.

ABSTRACT: BACKGROUND: Although hyperinsulinemia and insulin resistance have been hypothesized to be involved in pancreatic carcinogenesis, studies that have examined glycemic load or individual dietary components that influence glucose concentrations yielded inconclusive results. OBJECTIVE: Our objective was to investigate whether dietary insulin load and dietary insulin index are associated with the risk of pancreatic cancer. DESIGN: We prospectively followed 86,740 women and 46,147 men who were free of cancer and diabetes at baseline in the Nurses' Health Study and the Health Professionals Follow-Up Study. During ≤26 y of follow-up, 691 pancreatic cancer cases were documented. Dietary insulin load was calculated as a function of the food insulin index, and the energy content of individual foods was reported on food-frequency questionnaires. The dietary insulin index was calculated by dividing the dietary insulin load by the total energy intake. RESULTS: Dietary insulin load and dietary insulin index were not associated with the overall risk of pancreatic cancer. In a comparison of the highest with the lowest quintiles, the pooled multivariate RRs of pancreatic cancer were 1.05 (95% CI: 0.82, 1.34) for dietary insulin load and 0.96 (95% CI: 0.75, 1.23) for dietary insulin index. In individuals with an elevated BMI (in kg/m(2); ≥27.5) or with low physical activity, a high insulin load was associated with small, nonsignificant increases in the risk of pancreatic cancer; in a comparison of the highest with the lowest tertile of intake, the positive association became more apparent in those who were both overweight and inactive (RR: 2.03; 95% CI: 1.05, 3.93; P-trend = 0.04). CONCLUSIONS: A diet that induces an elevated postprandial insulin response does not influence the overall risk of pancreatic cancer. However, a diet with a high insulin load may increase the risk in individuals with a preexisting state of insulin resistance.