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Pancreatic Neoplasms: HELP
Articles by Kari G. Rabe
Based on 21 articles published since 2010
(Why 21 articles?)
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Between 2010 and 2020, Kari G. Rabe wrote the following 21 articles about Pancreatic Neoplasms.
 
+ Citations + Abstracts
1 Article Pancreatic cancer and melanoma related perceptions and behaviors following disclosure of CDKN2A variant status as a research result. 2019

Leof, Emma R / Zhu, Xuan / Rabe, Kari G / McCormick, Jennifer B / Petersen, Gloria M / Radecki Breitkopf, Carmen. ·Infectious Disease Epidemiology, Prevention and Control Division, Minnesota Department of Health, Saint Paul, MN, USA. · Department of Health Sciences Research, Mayo Clinic College of Medicine and Science, Mayo Clinic, Rochester, MN, USA. · Department of Humanities, College of Medicine, Pennsylvania State University, Hershey, PA, USA. · Department of Health Sciences Research, Mayo Clinic College of Medicine and Science, Mayo Clinic, Rochester, MN, USA. radeckibreitkopf.carmen@mayo.edu. ·Genet Med · Pubmed #30992552.

ABSTRACT: PURPOSE: This study examined whether participants who learned research results related to a germline CDKN2A variant known to be associated with increased risk of pancreatic cancer and malignant melanoma would pursue confirmatory testing and cancer screening, share the genetic information with health care providers and family, and change risk perceptions. METHODS: Participants were pancreas research registry enrollees whose biological sample was tested in a research laboratory for the variant. In total, 133 individuals were invited to learn a genetic research result and participate in a study about the disclosure process. Perceived cancer risk, screening intentions, and behaviors were assessed predisclosure, immediately postdisclosure, and six months postdisclosure. RESULTS: Eighty individuals agreed to participate and 63 completed the study. Immediately postdisclosure, carriers reported greater intentions to undergo pancreatic cancer and melanoma screening (p values ≤0.024). Seventy-three percent of carriers (47.5% noncarriers) intended to seek confirmatory testing within six months and 20% (2.5% noncarriers) followed through. All participants shared results with ≥1 family member. More carriers shared results with their health care provider than noncarriers (p = 0.028). CONCLUSION: Recipients of cancer genetic research results may not follow through with recommended behaviors (confirmatory testing, screening), despite stated intentions. The research result disclosure motivated follow-up behaviors among carriers more than noncarriers.

2 Article Psychological Impact of Learning CDKN2A Variant Status as a Genetic Research Result. 2018

Zhu, Xuan / Leof, Emma R / Rabe, Kari G / McCormick, Jennifer B / Petersen, Gloria M / Radecki Breitkopf, Carmen. ·Department of Health Sciences Research, Mayo Clinic, Rochester, Minnesota, USA. · Infectious Disease Epidemiology, Prevention, and Control Division, Minnesota Department of Health, St. Paul, Minnesota, USA. · Department of Humanities, College of Medicine, Pennsylvania State University, Hershey, Pennsylvania, USA. · Department of Health Sciences Research, Mayo Clinic, Rochester, Minnesota, USA, RadeckiBreitkopf.Carmen@mayo.edu. ·Public Health Genomics · Pubmed #30999302.

ABSTRACT: OBJECTIVES: Little is known about genetic research participants' responses to receiving individual research results (IRR) from cancer genetic research. We examined the immediate and delayed psychological impact of returning a CDKN2A variant result that is associated with increased risk of pancreatic cancer and melanoma. METHODS: One hundred and thirty-three pancreas research registry enrollees whose samples were tested in a research laboratory for the CDKN2A variant were invited by mail to learn the result by telephone and participate in a study about the disclosure process. Self-rated health, quality of life, and emotional responses were surveyed before and 6 months after disclosure. Genetic testing-specific distress, uncertainty, and positive experiences were assessed 6 months after disclosure. RESULTS: Eighty individuals agreed to participate; 63 completed the study. Both carriers and noncarriers showed no change over time in self-rated health, quality of life, or anxiety levels. Carriers reported more sadness than noncarriers before and 6 months after disclosure. Both carriers and noncarriers showed more hopefulness 6 months after than before disclosure. Carriers experienced greater test-specific distress and uncertainty than noncarriers, but levels were low. -Conclusions: Return of IRR in conjunction with cancer prevention counseling led to low levels of test-specific distress and uncertainty among carriers. No other adverse psychological outcomes were observed.

3 Article Metformin suppresses pancreatic tumor growth with inhibition of NFκB/STAT3 inflammatory signaling. 2015

Tan, Xiang-Lin / Bhattacharyya, Kalyan K / Dutta, Shamit K / Bamlet, William R / Rabe, Kari G / Wang, Enfeng / Smyrk, Thomas C / Oberg, Ann L / Petersen, Gloria M / Mukhopadhyay, Debabrata. ·From the *Division of Epidemiology, Department of Health Sciences Research, Mayo Clinic, Rochester, MN; †Rutgers Cancer Institute of New Jersey, Rutgers, The State University of New Jersey, New Brunswick; ‡Department of Epidemiology, School of Public Health, Rutgers, The State University of New Jersey, Piscataway, NJ; and §Department of Biochemistry and Molecular Biology, ∥Division of Biomedical Statistics and Informatics, Department of Health Sciences Research, and ¶Division of Anatomic Pathology, Mayo Clinic, Rochester, MN. ·Pancreas · Pubmed #25875801.

ABSTRACT: OBJECTIVES: To further elucidate the anticancer mechanisms of metformin against pancreatic cancer, we evaluated the inhibitory effects of metformin on pancreatic tumorigenesis in a genetically engineered mouse model and investigated its possible anti-inflammatory and antiangiogenesis effects. METHODS: Six-week-old LSL-Kras;Trp53 mice (10 per group) were administered once daily intraperitoneally with saline (control) for 1 week or metformin (125 mg/kg) for 1 week (Met_1wk) or 3 weeks (Met_3wk) before tumor initiation. All mice continued with their respective injections for 6 weeks after tumor initiation. Molecular changes were evaluated through quantitative polymerase chain reaction, immunohistochemistry, and Western blotting. RESULTS: At euthanasia, pancreatic tumor volume in the Met_1wk (median, 181.8 mm) and Met_3wk (median, 137.9 mm) groups was significantly lower than those in the control group (median, 481.1 mm; P = 0.001 and 0.0009, respectively). No significant difference was observed between the Met_1wk and Met_3wk groups (P = 0.51). These results were further confirmed using tumor weight and tumor burden measurements. Furthermore, metformin treatment decreased the phosphorylation of nuclear factor κB and signal transducer and activator of transcription 3 as well as the expression of specificity protein 1 transcription factor and several nuclear factor κB-regulated genes. CONCLUSIONS: Metformin may inhibit pancreatic tumorigenesis by modulating multiple molecular targets in inflammatory pathways.

4 Article Do variants associated with susceptibility to pancreatic cancer and type 2 diabetes reciprocally affect risk? 2015

Wu, Lang / Rabe, Kari G / Petersen, Gloria M. ·Department of Health Sciences Research, Mayo Clinic, Rochester, Minnesota, United States of America; Center for Clinical and Translational Science; Mayo Clinic, Rochester, Minnesota, United States of America. · Department of Health Sciences Research, Mayo Clinic, Rochester, Minnesota, United States of America. ·PLoS One · Pubmed #25658847.

ABSTRACT: OBJECTIVES: Although type 2 diabetes mellitus is a known risk factor for pancreatic cancer, the existence of shared genetic susceptibility is largely unknown. We evaluated whether any reported genetic risk variants of either disease found by genome-wide association studies reciprocally confer susceptibility. METHODS: Data that were generated in previous genome-wide association studies (GENEVA Type 2 Diabetes; PanScan) were obtained through the National Institutes of Health database of Genotypes and Phenotypes (dbGaP). Using the PanScan datasets, we tested for association of 38 variants within 37 genomic regions known to be susceptibility factors for type 2 diabetes. We further examined whether type 2 diabetes variants predispose to pancreatic cancer risk stratified by diabetes status. Correspondingly, we examined the association of fourteen pancreatic cancer susceptibility variants within eight genomic regions in the GENEVA Type 2 Diabetes dataset. RESULTS: Four plausible associations of diabetes variants and pancreatic cancer risk were detected at a significance threshold of p = 0.05, and one pancreatic cancer susceptibility variant was associated with diabetes risk at threshold of p = 0.05, but none remained significant after correction for multiple comparisons. CONCLUSION: Currently identified GWAS susceptibility variants are unlikely to explain the potential shared genetic etiology between Type 2 diabetes and pancreatic cancer.

5 Article BRCA1, BRCA2, PALB2, and CDKN2A mutations in familial pancreatic cancer: a PACGENE study. 2015

Zhen, David B / Rabe, Kari G / Gallinger, Steven / Syngal, Sapna / Schwartz, Ann G / Goggins, Michael G / Hruban, Ralph H / Cote, Michele L / McWilliams, Robert R / Roberts, Nicholas J / Cannon-Albright, Lisa A / Li, Donghui / Moyes, Kelsey / Wenstrup, Richard J / Hartman, Anne-Renee / Seminara, Daniela / Klein, Alison P / Petersen, Gloria M. ·Department of Internal Medicine, Mayo Clinic, Rochester, Minnesota, USA. · Department of Health Sciences Research, Mayo Clinic, Rochester, Minnesota, USA. · Divison of General Surgery, University of Toronto, Toronto, Ontario, Canada. · Population Sciences Division, Dana-Farber Cancer Institute, and Gastroenterology Division, Brigham and Women's Hospital, Boston, Massachusetts, USA. · Department of Oncology, Karmanos Cancer Institute and Wayne State University, Detroit, Michigan, USA. · The Sol Goldman Pancreatic Cancer Research Center, Department of Pathology, Johns Hopkins University, Baltimore, Maryland, USA. · Department of Oncology, Mayo Clinic, Rochester, Minnesota, USA. · 1] The Sol Goldman Pancreatic Cancer Research Center, Department of Pathology, Johns Hopkins University, Baltimore, Maryland, USA [2] Ludwig Center for Cancer Genetics, Johns Hopkins University, Baltimore, Maryland, USA. · Division of Genetic Epidemiology, University of Utah School of Medicine, Salt Lake City, Utah, USA. · Department of Gastrointestinal Medical Oncology, University of Texas MD Anderson Cancer Center, Houston, Texas, USA. · Myriad Genetic Laboratories, Inc., Salt Lake City, Utah, USA. · Division of Cancer Control and Population Sciences, National Cancer Institute, Bethesda, Maryland, USA. ·Genet Med · Pubmed #25356972.

ABSTRACT: PURPOSE: Familial pancreatic cancer kindreds contain at least two affected first-degree relatives. Comprehensive data are needed to assist clinical risk assessment and genetic testing. METHODS: Germ-line DNA samples from 727 unrelated probands with positive family history (521 met criteria for familial pancreatic cancer) were tested in compliance with the Clinical Laboratory Improvement Amendments for mutations in BRCA1 and BRCA2 (including analysis of deletions and rearrangements), PALB2, and CDKN2A. We compared prevalence of deleterious mutations between familial pancreatic cancer probands and nonfamilial pancreatic cancer probands (kindreds containing at least two affected biological relatives, but not first-degree relatives). We also examined the impact of family history on breast and ovarian cancers and melanoma. RESULTS: Prevalence of deleterious mutations (excluding variants of unknown significance) among familial pancreatic cancer probands was: BRCA1, 1.2%; BRCA2, 3.7%; PALB2, 0.6%; and CDKN2A, 2.5%. Four novel deleterious mutations were detected. Familial pancreatic cancer probands carry more mutations in the four genes (8.0%) than nonfamilial pancreatic cancer probands (3.5%) (odds ratio: 2.40; 95% confidence interval: 1.06-5.44; P = 0.03). The probability of testing positive for deleterious mutations in any of the four genes ranges up to 10.4%, depending on family history of cancers. BRCA2 and CDKN2A account for the majority of mutations in familial pancreatic cancer. CONCLUSION: Genetic testing of multiple relevant genes in probands with a positive family history is warranted, particularly for familial pancreatic cancer.

6 Article Risk factors for pancreatic neuroendocrine tumors: a clinic-based case-control study. 2014

Halfdanarson, Thorvardur R / Bamlet, William R / McWilliams, Robert R / Hobday, Timothy J / Burch, Patrick A / Rabe, Kari G / Petersen, Gloria M. ·From the *Division of Hematology and Medical Oncology, Mayo Clinic Arizona, Scottsdale, AZ; †Division of Medical Oncology; and ‡Department of Health Sciences Research, Mayo Clinic College of Medicine, Rochester, MN. ·Pancreas · Pubmed #25291526.

ABSTRACT: OBJECTIVES: Pancreatic neuroendocrine tumors (PNETs) are uncommon, and little is known about their risk factors and association with other cancers. We evaluated whether the following risk factors known to be associated with pancreatic adenocarcinoma are also associated with PNETs: smoking, alcohol use, family history of PNET, and other cancers, and personal history of diabetes as potential risk factors. METHODS: Patients with PNETs seen at Mayo Clinic Rochester between 2000 and 2011 were compared with controls seen for a general medical evaluation. Patients and controls completed the same questionnaires. After excluding insulinoma and high-grade PNETs, 355 cases were evaluated, and 309 were matched to 602 controls (2:1) on age, sex, and region of residence. RESULTS: Personal smoking history was not associated with PNETs. Alcohol use was less common among cases (54% vs 67%, P < 0.001). Cases were more likely to report a family member with sarcoma (P = 0.02), PNET (P = 0.02), gallbladder cancer (P = 0.02), ovarian cancer (P = 0.04), and gastric cancer (P = 0.01). There was no association with other cancers in family members. Diabetes was more commonly reported by cases than controls (19% vs 11%, P < 0.001). CONCLUSIONS: With the exception of diabetes, risk factors that are associated with pancreatic adenocarcinoma are not risk factors for PNETs.

7 Article Impact of diabetes mellitus on clinical outcomes in patients undergoing surgical resection for pancreatic cancer: a retrospective, cohort study. 2014

Hart, Phil A / Law, Ryan J / Frank, Ryan D / Bamlet, William R / Burch, Patrick A / Petersen, Gloria M / Rabe, Kari G / Chari, Suresh T. ·1] Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota, USA [2] Present address: Division of Gastroenterology, Hepatology, and Nutrition, Ohio State University Wexner Medical Center, Columbus, Ohio, USA. · Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota, USA. · Department of Health Sciences Research, Mayo Clinic, Rochester, Minnesota, USA. ·Am J Gastroenterol · Pubmed #25070053.

ABSTRACT: OBJECTIVES: Diabetes mellitus (DM) has a bidirectional association with pancreatic cancer (PaC); however, its effect on clinical outcomes has not been thoroughly evaluated. We analyzed these data in a large sample of PaC subjects who had undergone surgical resection. METHODS: Subjects enrolled in the Mayo Clinic Pancreatic Cancer SPORE registry from 2000 to 2010 who had resection with curative intent were identified (n=488). Tumor size, cancer stage, and postoperative median survival were evaluated. Median survivals were compared with Kaplan-Meier curves and Cox proportional hazards regression modeling. RESULTS: A total of 275 (56%) subjects had DM before surgery. DM subjects had larger tumors compared with those without DM (3.6 cm vs. 3.3, P=0.002), even after controlling for covariates including age, body mass index, and tumor grade. Cancer stage at the time of surgery was not affected by DM status (P=0.575). Preoperative DM was not associated with an increased risk of death using a multivariable survival analysis (hazard ratio 1.06, 95% confidence interval 0.81-1.38, P=0.676). The median survival following cancer resection was similar between subjects with and without DM (24 vs. 26 months, P=0.610). In addition, postoperative survival was similar on the basis of the duration of DM (new-onset vs. long-standing) and prior use of antidiabetic treatments in diabetic subjects. CONCLUSIONS: PaC subjects with DM have larger tumors than nondiabetic subjects. Despite this observation, preoperative DM does not negatively impact the cancer stage at the time of surgery or postoperative survival. Thus, the effect of DM on tumor size is either overshadowed by early metastatic spread of the cancer or is mitigated by the tumor resection.

8 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.

9 Article Fatty acids found in dairy, protein and unsaturated fatty acids are associated with risk of pancreatic cancer in a case-control study. 2014

Jansen, Rick J / Robinson, Dennis P / Frank, Ryan D / Anderson, Kristin E / Bamlet, William R / Oberg, Ann L / Rabe, Kari G / Olson, Janet E / Sinha, Rashmi / Petersen, Gloria M / Stolzenberg-Solomon, Rachael Z. ·Division of Epidemiology Department of Health Sciences Research, Mayo Clinic, Rochester, MN. ·Int J Cancer · Pubmed #24590454.

ABSTRACT: Although many studies have investigated meat and total fat in relation to pancreatic cancer risk, few have investigated dairy, fish and specific fatty acids (FAs). We evaluated the association between intake of meat, fish, dairy, specific FAs and related nutrients and pancreatic cancer. In our American-based Mayo Clinic case-control study 384 cases and 983 controls frequency matched on recruitment age, race, sex and residence area (Minnesota, Wisconsin or Iowa, USA) between 2004 and 2009. All subjects provided demographic information and completed 144-item food frequency questionnaire. Logistic regression-calculated odds ratios (ORs) and 95% confidence intervals (95% CIs) were adjusted for age, sex, cigarette smoking, body mass index and diabetes mellitus. Significant inverse association (trend p-value < 0.05) between pancreatic cancer and the groupings (highest vs. lowest consumption quintile OR [95% CI]) was as follows: meat replacement (0.67 [0.43-1.02]), total protein (0.58 [0.39-0.86]), vitamin B12 (0.67 [0.44, 1.01]), zinc (0.48 [0.32, 0.71]), phosphorus (0.62 [0.41, 0.93]), vitamin E (0.51 [0.33, 0.78]), polyunsaturated FAs (0.64 [0.42, 0.98]) and linoleic acid (FA 18:2) (0.62 [0.40-0.95]). Increased risk associations were observed for saturated FAs (1.48 [0.97-2.23]), butyric acid (FA 4:0) (1.77 [1.19-2.64]), caproic acid (FA 6:0) (2.15 [1.42-3.27]), caprylic acid (FA 8:0) (1.87 [1.27-2.76]) and capric acid (FA 10:0) (1.83 [1.23-2.74]). Our study suggests that eating a diet high in total protein and certain unsaturated FAs is associated with decreased risk of developing pancreatic cancer in a dose-dependent manner, whereas fats found in dairy increase risk.

10 Article An absolute risk model to identify individuals at elevated risk for pancreatic cancer in the general population. 2013

Klein, Alison P / Lindström, Sara / Mendelsohn, Julie B / Steplowski, Emily / Arslan, Alan A / Bueno-de-Mesquita, H Bas / Fuchs, Charles S / Gallinger, Steven / Gross, Myron / Helzlsouer, Kathy / Holly, Elizabeth A / Jacobs, Eric J / Lacroix, Andrea / Li, Donghui / Mandelson, Margaret T / Olson, Sara H / Petersen, Gloria M / Risch, Harvey A / Stolzenberg-Solomon, Rachael Z / Zheng, Wei / Amundadottir, Laufey / Albanes, Demetrius / Allen, Naomi E / Bamlet, William R / Boutron-Ruault, Marie-Christine / Buring, Julie E / Bracci, Paige M / Canzian, Federico / Clipp, Sandra / Cotterchio, Michelle / Duell, Eric J / Elena, Joanne / Gaziano, J Michael / Giovannucci, Edward L / Goggins, Michael / Hallmans, Göran / Hassan, Manal / Hutchinson, Amy / Hunter, David J / Kooperberg, Charles / Kurtz, Robert C / Liu, Simin / Overvad, Kim / Palli, Domenico / Patel, Alpa V / Rabe, Kari G / Shu, Xiao-Ou / Slimani, Nadia / Tobias, Geoffrey S / Trichopoulos, Dimitrios / Van Den Eeden, Stephen K / Vineis, Paolo / Virtamo, Jarmo / Wactawski-Wende, Jean / Wolpin, Brian M / Yu, Herbert / Yu, Kai / Zeleniuch-Jacquotte, Anne / Chanock, Stephen J / Hoover, Robert N / Hartge, Patricia / Kraft, Peter. ·Department of Oncology, Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, Maryland, United States of America ; Department of Pathology, Sol Goldman Pancreatic Cancer Research Center, Johns Hopkins School of Medicine, Baltimore, Maryland, United States of America ; Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, United States of America. ·PLoS One · Pubmed #24058443.

ABSTRACT: PURPOSE: We developed an absolute risk model to identify individuals in the general population at elevated risk of pancreatic cancer. PATIENTS AND METHODS: Using data on 3,349 cases and 3,654 controls from the PanScan Consortium, we developed a relative risk model for men and women of European ancestry based on non-genetic and genetic risk factors for pancreatic cancer. We estimated absolute risks based on these relative risks and population incidence rates. RESULTS: Our risk model included current smoking (multivariable adjusted odds ratio (OR) and 95% confidence interval: 2.20 [1.84-2.62]), heavy alcohol use (>3 drinks/day) (OR: 1.45 [1.19-1.76]), obesity (body mass index >30 kg/m(2)) (OR: 1.26 [1.09-1.45]), diabetes >3 years (nested case-control OR: 1.57 [1.13-2.18], case-control OR: 1.80 [1.40-2.32]), family history of pancreatic cancer (OR: 1.60 [1.20-2.12]), non-O ABO genotype (AO vs. OO genotype) (OR: 1.23 [1.10-1.37]) to (BB vs. OO genotype) (OR 1.58 [0.97-2.59]), rs3790844(chr1q32.1) (OR: 1.29 [1.19-1.40]), rs401681(5p15.33) (OR: 1.18 [1.10-1.26]) and rs9543325(13q22.1) (OR: 1.27 [1.18-1.36]). The areas under the ROC curve for risk models including only non-genetic factors, only genetic factors, and both non-genetic and genetic factors were 58%, 57% and 61%, respectively. We estimate that fewer than 3/1,000 U.S. non-Hispanic whites have more than a 5% predicted lifetime absolute risk. CONCLUSION: Although absolute risk modeling using established risk factors may help to identify a group of individuals at higher than average risk of pancreatic cancer, the immediate clinical utility of our model is limited. However, a risk model can increase awareness of the various risk factors for pancreatic cancer, including modifiable behaviors.

11 Article Polymorphisms in metabolism/antioxidant genes may mediate the effect of dietary intake on pancreatic cancer risk. 2013

Jansen, Rick J / Robinson, Dennis P / Stolzenberg-Solomon, Rachael Z / Bamlet, William R / Tan, XiangLin / Cunningham, Julie M / Li, Ying / Rider, David N / Oberg, Ann L / Rabe, Kari G / Anderson, Kristin E / Sinha, Rashmi / Petersen, Gloria M. ·From the Divisions of *Epidemiology, and †Biomedical Statistics and Informatics, Department of Health Sciences Research, Mayo Clinic, Rochester, MN; ‡Department of Epidemiology, National Institutes of Health, Bethesda, MD; §Department of Epidemiology and Community Health, University of Minnesota, Minneapolis, MN; and ∥Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD. ·Pancreas · Pubmed #24051964.

ABSTRACT: OBJECTIVES: A source of variation for inconsistent dietary-pancreatic cancer associations may be individuals carrying constitutional metabolism/antioxidant gene variants that differentially benefit compared to homozygous individuals. Seventy-six tag single-nucleotide polymorphisms were genotyped in 13 candidate genes to test differential associations with pancreatic adenocarcinoma. METHODS: A clinic-based case-control design was used to rapidly ascertain 251 cases and 970 frequency matched controls who provided blood samples and completed a 144-item food frequency questionnaire. Single-nucleotide polymorphisms were evaluated using a dominant genetic model and dietary categories split on controls' median intake. Logistic regression was used to calculate odds ratios and 95% confidence intervals, adjusted for potential confounders. RESULTS: Significant increased associations (Bonferroni corrected P ≤ 0.0007) were observed for carriers of greater than or equal to 1 minor allele for rs3816257 (glucosidase, α; acid [GAA]) and lower intake of deep-yellow vegetables (1.90 [1.28-2.83]); and carriers of no minor allele for rs12807961 (catalase [CAT]) and high total grains intake (2.48 [1.50-4.09]), whereas those with greater than or equal to 1 minor allele had a decreasing slope (across grains). The reference group was no minor alleles with low dietary intake. CONCLUSIONS: Interindividual variation in metabolism/antioxidant genes could interact with dietary intake to influence pancreatic cancer risk.

12 Article Meat-related mutagens and pancreatic cancer: null results from a clinic-based case-control study. 2013

Jansen, Rick J / Robinson, Dennis P / Frank, Ryan D / Stolzenberg-Solomon, Rachael Z / Bamlet, William R / Oberg, Ann L / Rabe, Kari G / Olson, Janet E / Petersen, Gloria M / Sinha, Rashmi / Anderson, Kristin E. ·Division of Epidemiology, Department of Health Sciences Research, Mayo Clinic, Rochester, MN 55905, USA. ·Cancer Epidemiol Biomarkers Prev · Pubmed #23632817.

ABSTRACT: BACKGROUND: Pancreatic cancer is a devastating disease for which the role of dietary factors remains inconclusive. The study objective was to evaluate risk of pancreatic cancer associated with meat preparation methods and meat-related mutagen consumption using a clinic-based case-control design. METHODS: There were 384 cases and 983 controls; subjects provided demographic information and completed a 144-item food frequency questionnaire, which was used to estimate meat mutagen intake using the National Cancer Institute's CHARRED database (Bethesda, MD). Logistic regression was used to calculate ORs and 95% confidence intervals (CI), adjusted for factors including age, sex, cigarette smoking, body mass index, and diabetes mellitus. RESULTS: Overall, the findings were null with respect to meat mutagen intake and pancreatic cancer. CONCLUSIONS: The results do not support an association between well-done meat or meat-related mutagen intake and pancreatic cancer and contrast with generally increased risks reported in previous studies. IMPACT: These data contribute to evidence about pancreatic cancer and potentially carcinogenic compounds in meat.

13 Article Nutrients from fruit and vegetable consumption reduce the risk of pancreatic cancer. 2013

Jansen, Rick J / Robinson, Dennis P / Stolzenberg-Solomon, Rachael Z / Bamlet, William R / de Andrade, Mariza / Oberg, Ann L / Rabe, Kari G / Anderson, Kristin E / Olson, Janet E / Sinha, Rashmi / Petersen, Gloria M. ·Division of Epidemiology, Department of Health Sciences Research, Mayo Clinic, 200 First Street SW, Rochester, MN 55905, USA. jansen.rick@mayo.edu ·J Gastrointest Cancer · Pubmed #23620017.

ABSTRACT: PURPOSE: Pancreatic cancer is a devastating disease for which the role of dietary factors remains inconclusive. Our objective was to evaluate the risk of pancreatic cancer associated with nutrients found in fruits and vegetables and nutrient supplementation using a clinic-based case-control design. METHODS: Our study included 384 rapidly ascertained cases and 983 controls frequency-matched on age at time of recruitment (in 5-year increments), race, sex, and region of residence. All subjects provided demographic information and completed a 144-item food frequency questionnaire in which they reported no change to their diet within 5 years prior to entering the study. Logistic regression was used to calculate odds ratios and 95 % confidence intervals, adjusted for age, sex, smoking, body mass index, energy intake, and alcohol consumption. RESULTS: Results show a significant (trend p value < 0.05) inverse association between pancreatic cancer and nutrient/supplement groupings in a dose-dependent manner including magnesium, potassium, selenium, alpha-carotene, beta-carotene, beta-cryptoxanthin, lutein and zeaxanthin, niacin, total alpha-tocopherol, total vitamin A activity, vitamin B6, and vitamin C. Adjusting for diabetes or total sugar intake did not result in significant changes. CONCLUSION: We conclude that most nutrients obtained through consumption of fruits and vegetables may reduce the risk of developing pancreatic cancer.

14 Article Polymorphisms in genes related to one-carbon metabolism are not related to pancreatic cancer in PanScan and PanC4. 2013

Leenders, Max / Bhattacharjee, Samsiddhi / Vineis, Paolo / Stevens, Victoria / Bueno-de-Mesquita, H Bas / Shu, Xiao-Ou / Amundadottir, Laufey / Gross, Myron / Tobias, Geoffrey S / Wactawski-Wende, Jean / Arslan, Alan A / Duell, Eric J / Fuchs, Charles S / Gallinger, Steven / Hartge, Patricia / Hoover, Robert N / Holly, Elizabeth A / Jacobs, Eric J / Klein, Alison P / Kooperberg, Charles / LaCroix, Andrea / Li, Donghui / Mandelson, Margaret T / Olson, Sara H / Petersen, Gloria / Risch, Harvey A / Yu, Kai / Wolpin, Brian M / Zheng, Wei / Agalliu, Ilir / Albanes, Demetrius / Boutron-Ruault, Marie-Christine / Bracci, Paige M / Buring, Julie E / Canzian, Federico / Chang, Kenneth / Chanock, Stephen J / Cotterchio, Michelle / Gaziano, J Michael / Giovanucci, Edward L / Goggins, Michael / Hallmans, Göran / Hankinson, Susan E / Hoffman-Bolton, Judith A / Hunter, David J / Hutchinson, Amy / Jacobs, Kevin B / Jenab, Mazda / Khaw, Kay-Tee / Kraft, Peter / Krogh, Vittorio / Kurtz, Robert C / McWilliams, Robert R / Mendelsohn, Julie B / Patel, Alpa V / Rabe, Kari G / Riboli, Elio / Tjønneland, Anne / Trichopoulos, Dimitrios / Virtamo, Jarmo / Visvanathan, Kala / Elena, Joanne W / Yu, Herbert / Zeleniuch-Jacquotte, Anne / Stolzenberg-Solomon, Rachael Z. ·Department of Epidemiology and Biostatistics, School of Public Health, Imperial College, London, UK. M.Leenders-6@umcutrecht.nl ·Cancer Causes Control · Pubmed #23334854.

ABSTRACT: PURPOSE: The evidence of a relation between folate intake and one-carbon metabolism (OCM) with pancreatic cancer (PanCa) is inconsistent. In this study, the association between genes and single-nucleotide polymorphisms (SNPs) related to OCM and PanCa was assessed. METHODS: Using biochemical knowledge of the OCM pathway, we identified thirty-seven genes and 834 SNPs to examine in association with PanCa. Our study included 1,408 cases and 1,463 controls nested within twelve cohorts (PanScan). The ten SNPs and five genes with lowest p values (<0.02) were followed up in 2,323 cases and 2,340 controls from eight case-control studies (PanC4) that participated in PanScan2. The correlation of SNPs with metabolite levels was assessed for 649 controls from the European Prospective Investigation into Cancer and Nutrition. RESULTS: When both stages were combined, we observed suggestive associations with PanCa for rs10887710 (MAT1A) (OR 1.13, 95 %CI 1.04-1.23), rs1552462 (SYT9) (OR 1.27, 95 %CI 1.02-1.59), and rs7074891 (CUBN) (OR 1.91, 95 %CI 1.12-3.26). After correcting for multiple comparisons, no significant associations were observed in either the first or second stage. The three suggested SNPs showed no correlations with one-carbon biomarkers. CONCLUSIONS: This is the largest genetic study to date to examine the relation between germline variations in OCM-related genes polymorphisms and the risk of PanCa. Suggestive evidence for an association between polymorphisms and PanCa was observed among the cohort-nested studies, but this did not replicate in the case-control studies. Our results do not strongly support the hypothesis that genes related to OCM play a role in pancreatic carcinogenesis.

15 Article Identification of germline genomic copy number variation in familial pancreatic cancer. 2012

Al-Sukhni, Wigdan / Joe, Sarah / Lionel, Anath C / Zwingerman, Nora / Zogopoulos, George / Marshall, Christian R / Borgida, Ayelet / Holter, Spring / Gropper, Aaron / Moore, Sara / Bondy, Melissa / Klein, Alison P / Petersen, Gloria M / Rabe, Kari G / Schwartz, Ann G / Syngal, Sapna / Scherer, Stephen W / Gallinger, Steven. ·Samuel Lunenfeld Research Institute, Mount Sinai Hospital, Toronto, ON, Canada. wigdan.al.sukhni@utoronto.ca ·Hum Genet · Pubmed #22665139.

ABSTRACT: Adenocarcinoma of the pancreas is a significant cause of cancer mortality, and up to 10 % of cases appear to be familial. Heritable genomic copy number variants (CNVs) can modulate gene expression and predispose to disease. Here, we identify candidate predisposition genes for familial pancreatic cancer (FPC) by analyzing germline losses or gains present in one or more high-risk patients and absent in a large control group. A total of 120 FPC cases and 1,194 controls were genotyped on the Affymetrix 500K array, and 36 cases and 2,357 controls were genotyped on the Affymetrix 6.0 array. Detection of CNVs was performed by multiple computational algorithms and partially validated by quantitative PCR. We found no significant difference in the germline CNV profiles of cases and controls. A total of 93 non-redundant FPC-specific CNVs (53 losses and 40 gains) were identified in 50 cases, each CNV present in a single individual. FPC-specific CNVs overlapped the coding region of 88 RefSeq genes. Several of these genes have been reported to be differentially expressed and/or affected by copy number alterations in pancreatic adenocarcinoma. Further investigation in high-risk subjects may elucidate the role of one or more of these genes in genetic predisposition to pancreatic cancer.

16 Article Pathway analysis of genome-wide association study data highlights pancreatic development genes as susceptibility factors for pancreatic cancer. 2012

Li, Donghui / Duell, Eric J / Yu, Kai / Risch, Harvey A / Olson, Sara H / Kooperberg, Charles / Wolpin, Brian M / Jiao, Li / Dong, Xiaoqun / Wheeler, Bill / Arslan, Alan A / Bueno-de-Mesquita, H Bas / Fuchs, Charles S / Gallinger, Steven / Gross, Myron / Hartge, Patricia / Hoover, Robert N / Holly, Elizabeth A / Jacobs, Eric J / Klein, Alison P / LaCroix, Andrea / Mandelson, Margaret T / Petersen, Gloria / Zheng, Wei / Agalliu, Ilir / Albanes, Demetrius / Boutron-Ruault, Marie-Christine / Bracci, Paige M / Buring, Julie E / Canzian, Federico / Chang, Kenneth / Chanock, Stephen J / Cotterchio, Michelle / Gaziano, J Michael / Giovannucci, Edward L / Goggins, Michael / Hallmans, Göran / Hankinson, Susan E / Hoffman Bolton, Judith A / Hunter, David J / Hutchinson, Amy / Jacobs, Kevin B / Jenab, Mazda / Khaw, Kay-Tee / Kraft, Peter / Krogh, Vittorio / Kurtz, Robert C / McWilliams, Robert R / Mendelsohn, Julie B / Patel, Alpa V / Rabe, Kari G / Riboli, Elio / Shu, Xiao-Ou / Tjønneland, Anne / Tobias, Geoffrey S / Trichopoulos, Dimitrios / Virtamo, Jarmo / Visvanathan, Kala / Watters, Joanne / Yu, Herbert / Zeleniuch-Jacquotte, Anne / Amundadottir, Laufey / Stolzenberg-Solomon, Rachael Z. ·Department of Gastrointestinal Medical Oncology, The University of Texas M. D. Anderson Cancer Center, Houston, TX, USA. ·Carcinogenesis · Pubmed #22523087.

ABSTRACT: Four loci have been associated with pancreatic cancer through genome-wide association studies (GWAS). Pathway-based analysis of GWAS data is a complementary approach to identify groups of genes or biological pathways enriched with disease-associated single-nucleotide polymorphisms (SNPs) whose individual effect sizes may be too small to be detected by standard single-locus methods. We used the adaptive rank truncated product method in a pathway-based analysis of GWAS data from 3851 pancreatic cancer cases and 3934 control participants pooled from 12 cohort studies and 8 case-control studies (PanScan). We compiled 23 biological pathways hypothesized to be relevant to pancreatic cancer and observed a nominal association between pancreatic cancer and five pathways (P < 0.05), i.e. pancreatic development, Helicobacter pylori lacto/neolacto, hedgehog, Th1/Th2 immune response and apoptosis (P = 2.0 × 10(-6), 1.6 × 10(-5), 0.0019, 0.019 and 0.023, respectively). After excluding previously identified genes from the original GWAS in three pathways (NR5A2, ABO and SHH), the pancreatic development pathway remained significant (P = 8.3 × 10(-5)), whereas the others did not. The most significant genes (P < 0.01) in the five pathways were NR5A2, HNF1A, HNF4G and PDX1 for pancreatic development; ABO for H.pylori lacto/neolacto; SHH for hedgehog; TGFBR2 and CCL18 for Th1/Th2 immune response and MAPK8 and BCL2L11 for apoptosis. Our results provide a link between inherited variation in genes important for pancreatic development and cancer and show that pathway-based approaches to analysis of GWAS data can yield important insights into the collective role of genetic risk variants in cancer.

17 Article New-onset diabetes in pancreatic cancer: a study in the primary care setting. 2012

Aggarwal, Gaurav / Rabe, Kari G / Petersen, Gloria M / Chari, Suresh T. ·Division of Gastroenterology and Hepatology, Mayo Clinic, 200 First Street SW, Rochester, MN 55905, USA. ·Pancreatology · Pubmed #22487526.

ABSTRACT: BACKGROUND: Onset of diabetes mellitus (DM) is often first noted by primary care physicians. New-onset DM (duration <36 months before PaC diagnosis) can be a harbinger of pancreatic cancer (PaC). However, its clinical significance remains unclear. METHODS: To determine the prevalence, onset, and delay in diagnosis of DM in PaC patients in the primary care setting, we retrospectively reviewed the records of consecutive patients followed in Mayo Clinic's primary care clinics (at least one visit in the preceding 2 years) from 1995 to 2009 who were eventually diagnosed with PaC. Onset of DM was the first date the fasting blood glucose was ≥126 mg/dl. RESULTS: Of the 111 PaC patients (59 male, median age 74 years), 52 (47%) had DM of whom 30 (58%) had new-onset DM. Among the 30 with new-onset DM, 24 (80%) were asymptomatic (no cancer-specific symptoms), at DM onset. In these 24 patients, median duration of DM prior to PaC diagnosis was 6.5 (0.5-35) months, and median delay between onset and physician diagnosis of DM was 2.5 (0.25-14) months, which decreased from 8.8 (3.5-14) months in patients with DM onset between 1995 and 1999 to 0 (0-2) months, in patients with DM onset between 2004 and 2009. However, the proportion of patients with undiagnosed DM (~33%) remained unchanged. CONCLUSIONS: Diabetes is very common (~50%) in PaC. In over a fifth of PaC, the onset of DM occurs when the cancer is asymptomatic, providing a potential window-of-opportunity to diagnose early PaC. However, nearly a third of new-onset DM in PaC remains undiagnosed.

18 Article Fruit and vegetable consumption is inversely associated with having pancreatic cancer. 2011

Jansen, Rick J / Robinson, Dennis P / Stolzenberg-Solomon, Rachael Z / Bamlet, William R / de Andrade, Mariza / Oberg, Ann L / Hammer, Traci J / Rabe, Kari G / Anderson, Kristin E / Olson, Janet E / Sinha, Rashmi / Petersen, Gloria M. ·Department of Health Sciences Research, Mayo Clinic, 200 First Street SW, Rochester, MN 55905, USA. Jansen.Rick@mayo.edu ·Cancer Causes Control · Pubmed #21915615.

ABSTRACT: OBJECTIVE: Studies on fruit, vegetable, fiber, and grain consumption and pancreatic cancer risk are inconclusive. We used a clinic-based case-control study specifically designed to address limitations of both cohort and case-control studies to examine the relationship. METHODS: Participants were excluded who reported changing their diet within 5 years prior to study entry. And 384 rapidly ascertained cases and 983 controls (frequency matched on age (±5 years), race, sex, and residence) completed epidemiologic surveys and 144-item food frequency questionnaires. Odds ratios (OR) and 95% confidence intervals were calculated using logistic regression adjusted for age, sex, smoking, body mass index, energy intake, and alcohol consumption. RESULTS: Comparing highest to lowest quintiles, we observed significant inverse associations (OR < 0.8) with significant trends (p (trend) < 0.05) for citrus, melon, and berries, other fruits, dark green vegetables, deep yellow vegetables, tomato, other vegetables, dry bean and pea, insoluble fiber, soluble fiber, whole grains, and orange/grapefruit juice, and an increased association with non-whole grains. Results were similar after adjusting for diabetes or total sugar intake. CONCLUSIONS: We provide evidence that lower consumption of fruits, vegetables, whole grains, and fiber is associated with having pancreatic cancer. This may have a role in developing prevention strategies.

19 Article Weight loss precedes cancer-specific symptoms in pancreatic cancer-associated diabetes mellitus. 2011

Hart, Phil A / Kamada, Pratima / Rabe, Kari G / Srinivasan, Sunil / Basu, Ananda / Aggarwal, Gaurav / Chari, Suresh T. ·Department of Internal Medicine, Mayo Clinic, Rochester, MN55905, USA. ·Pancreas · Pubmed #21654538.

ABSTRACT: OBJECTIVES: New-onset diabetes mellitus (DM) may herald pancreatic cancer (PaC). We determined whether changes in body weight distinguished PaC-associated DM (PaCDM) from type 2 DM. METHODS: Among Olmsted County residents, we identified 29 PaCDM and 43 type 2 DM subjects who had serial fasting blood glucose measurements, new-onset DM, and no cancer-specific symptoms at DM onset. We compared body weight (kg) and fasting blood glucose (mg/dL) at DM onset, 1 to 2 years before and at index date in the 2 groups. RESULTS: Fasting blood glucose values were similar before and at the onset of DM. Before onset of DM, PaCDM and type 2 DM subjects had similar body weight (P = 0.80). However, at onset of DM, 59% of PaCDM subjects lost weight versus 30% of type 2 DM subjects (P = 0.02). At onset of DM, 56% of type 2 DM subjects gained weight versus 31% of PaCDM subjects (P = 0.04). By index date, PaCDM subjects lost more weight than type 2 DM subjects did (8.3 ± 8.3 vs 0.8 ± 4.8 kg, P < 0.01). CONCLUSIONS: Although new-onset primary type 2 DM is typically associated with weight gain, weight loss frequently precedes onset of PaCDM. The paradoxical development of diabetes in the face of ongoing weight loss may be an important clue to understanding the pathogenesis of PaCDM.

20 Article Patterns of pancreatic resection differ between patients with familial and sporadic pancreatic cancer. 2011

Barton, Joshua G / Schnelldorfer, Thomas / Lohse, Christine M / Bamlet, William R / Rabe, Kari G / Petersen, Gloria M / Donohue, John H / Farnell, Michael B / Kendrick, Michael L / Nagorney, David M / Lombardo, Kay M Reid / Que, Florencia G. ·Division of GI and General Surgery, Mayo 12, 200 1st St. SW, Rochester, MN 55905, USA. ·J Gastrointest Surg · Pubmed #21359597.

ABSTRACT: BACKGROUND: Although the increased risk of developing pancreatic cancer (PC) in families with a strong history of the disease is well known, characteristics and outcomes of patients with familial PC is not described well. AIMS: This study aims to evaluate outcomes following resection in patients with familial PC. METHODS: We studied 208 patients who underwent resection of PC from 2000 to 2007 and had prospectively completed family history questionnaires for the Biospecimen Resource for Pancreas Research at our institution. We compared clinical characteristics and outcomes of familial and sporadic PC patients. RESULTS: Familial (N = 15) and sporadic PC patients (N = 193) did not have significantly different demographics, pre-operative CA19-9, pre-operative weight loss, R0 status, or T-staging (all p ≥ 0.05). Familial PC patients had lower pre-operative total serum bilirubin concentrations (p = 0.03) and lesions outside of the pancreatic head more frequently (p = 0.02) than sporadic PC patients. There was no difference in survival at 2 years between familial and sporadic PC patients (p = 0.52). CONCLUSIONS: Familial PC patients appear to develop tumors outside of the pancreatic head more frequently than sporadic PC patients. This difference in tumor distribution may be due to a broader area of cancer susceptibility within the pancreas for familial PC patients.

21 Article Prevalence of CDKN2A mutations in pancreatic cancer patients: implications for genetic counseling. 2011

McWilliams, Robert R / Wieben, Eric D / Rabe, Kari G / Pedersen, Katrina S / Wu, Yanhong / Sicotte, Hugues / Petersen, Gloria M. ·Department of Oncology, Mayo Clinic, Rochester, MN, USA. mcwilliams.robert@mayo.edu ·Eur J Hum Genet · Pubmed #21150883.

ABSTRACT: Germline mutations in CDKN2A have been reported in pancreatic cancer families, but genetic counseling for pancreatic cancer risk has been limited by lack of information on CDKN2A mutation carriers outside of selected pancreatic or melanoma kindreds. Lymphocyte DNA from consecutive, unselected white non-Hispanic patients with pancreatic adenocarcinoma was used to sequence CDKN2A. Frequencies of mutations that alter the coding of p16INK4 or p14ARF were quantified overall and in subgroups. Penetrance and likelihood of carrying mutations by family history were estimated. Among 1537 cases, 9 (0.6%) carried germline mutations in CDKN2A, including three previously unreported mutations. CDKN2A mutation carriers were more likely to have a family history of pancreatic cancer (P=0.003) or melanoma (P=0.03), and a personal history of melanoma (P=0.01). Among cases who reported having a first-degree relative with pancreatic cancer or melanoma, the carrier proportions were 3.3 and 5.3%, respectively. Penetrance for mutation carriers by age 80 was calculated to be 58% for pancreatic cancer (95% confidence interval (CI) 8-86%), and 39% for melanoma (95% CI 0-80). Among cases who ever smoked cigarettes, the risk for pancreatic cancer was higher for carriers compared with non-carriers (HR 25.8, P=2.1 × 10⁻¹³), but among nonsmokers, this comparison did not reach statistical significance. Germline mutations in CDKN2A among unselected pancreatic cancer patients are uncommon, although notably penetrant, especially among smokers. Carriers of germline mutations of CDKN2A should be counseled to avoid tobacco use to decrease risk of pancreatic cancer in addition to taking measures to decrease melanoma risk.