Is dietary fat, vitamin D, or folate associated with pancreatic cancer?

Although potentially modifiable risk factors for pancreatic cancer include smoking, obesity, and diabetes, less is known about the extent to which diet affects cancer risk. Recent studies have demonstrated some consistency for dietary fat being associated with elevated pancreatic cancer risk, particularly from animal sources. However, less is known about which fatty acids pose the greatest risk. Vitamin D, due to its endogenous production following UV‐B exposure, is a unique risk factor in that researchers have created several methods to assess its exposure in humans. Studies that measured vitamin D exposure differently have shown inconsistent results. Dietary studies suggest protective associations, whereas studies of circulating 25‐hydroxyvitamin D status show null or positive associations with low or very high concentrations, respectively. Several, but not all epidemiologic studies provide evidence of an inverse relationship between total and/or dietary folate and risk of pancreatic cancer. Protective associations for circulating folate are more often observed among populations with inadequate status. This article reviews the current epidemiological and experimental evidence investigating the relationship of dietary fat, vitamin D, and folate with pancreatic cancer. Additionally the mechanisms by which these risk factors may contribute to cancer, the methodological challenges involved with assessing risk, and other obstacles encountered when ascertaining the magnitude and direction of these three exposures are discussed. Published 2011. This article is a U.S. Government work and is in the public domain in the USA.

[1]  N. Dávila,et al.  Identification of a Vitamin D response element in the human insulin receptor gene promoter , 2003, The Journal of Steroid Biochemistry and Molecular Biology.

[2]  W. Willett,et al.  Dietary meat, dairy products, fat, and cholesterol and pancreatic cancer risk in a prospective study. , 2003, American journal of epidemiology.

[3]  W. Grant An estimate of premature cancer mortality in the U.S. due to inadequate doses of solar ultraviolet‐B radiation , 2002, Cancer.

[4]  Francis P Boscoe,et al.  Solar ultraviolet-B exposure and cancer incidence and mortality in the United States, 1993–2002 , 2006, BMC Cancer.

[5]  Young-In Kim Folic acid fortification and supplementation--good for some but not so good for others. , 2007, Nutrition reviews.

[6]  E. Giovannucci,et al.  Predicted vitamin D status and pancreatic cancer risk in two prospective cohort studies , 2010, British Journal of Cancer.

[7]  D. Albanes,et al.  Pancreatic cancer risk and nutrition-related methyl-group availability indicators in male smokers. , 1999, Journal of the National Cancer Institute.

[8]  A. Miller,et al.  A collaborative case‐control study of nutrient intake and pancreatic cancer within the search programme , 1992, International journal of cancer.

[9]  E. Holly,et al.  Pancreatic cancer, animal protein and dietary fat in a population-based study, San Francisco Bay Area, California , 2007, Cancer Causes & Control.

[10]  R. Jorde,et al.  Tracking of serum 25-hydroxyvitamin D levels during 14 years in a population-based study and during 12 months in an intervention study. , 2010, American journal of epidemiology.

[11]  R. Jaszewski,et al.  Folic acid supplementation inhibits recurrence of colorectal adenomas: a randomized chemoprevention trial. , 2008, World journal of gastroenterology.

[12]  B. Vessby Dietary fat and insulin action in humans , 2000, British Journal of Nutrition.

[13]  M. Willingham,et al.  Pancreatic cancer cells express 25-hydroxyvitamin D-1α-hydroxylase and their proliferation is inhibited by the prohormone 25-hydroxyvitamin D3 , 2004 .

[14]  R. Goldbohm,et al.  Meat and fat intake and pancreatic cancer risk in the Netherlands Cohort Study , 2009, International journal of cancer.

[15]  M. Saif,et al.  Role of Vitamin D in the Prevention of Pancreatic Cancer , 2011, Journal of nutrition and metabolism.

[16]  Wei-dong Yu,et al.  Calcitriol enhances gemcitabine antitumor activity in vitro and in vivo by promoting apoptosis in a human pancreatic carcinoma model system , 2010, Cell cycle.

[17]  E. Holly,et al.  Vitamin D, calcium, and retinol intake, and pancreatic cancer in a population-based case–control study in the San Francisco Bay area , 2010, Cancer Causes & Control.

[18]  Yan Liu,et al.  Prospective study of predictors of vitamin D status and cancer incidence and mortality in men. , 2006, Journal of the National Cancer Institute.

[19]  S. Larsson,et al.  Folate intake and pancreatic cancer incidence: a prospective study of Swedish women and men. , 2006, Journal of the National Cancer Institute.

[20]  D. Albanes,et al.  A prospective nested case-control study of vitamin D status and pancreatic cancer risk in male smokers. , 2006, Cancer research.

[21]  D. Silverman,et al.  Dietary fatty acids and pancreatic cancer in the NIH-AARP diet and health study. , 2009, Journal of the National Cancer Institute.

[22]  S. Mohr,et al.  Ultraviolet B Irradiance and Vitamin D Status are Inversely Associated With Incidence Rates of Pancreatic Cancer Worldwide , 2010, Pancreas.

[23]  M. Holick,et al.  Vitamin D status: measurement, interpretation, and clinical application. , 2009, Annals of epidemiology.

[24]  F. Clavel-Chapelon,et al.  A U-shaped relationship between plasma folate and pancreatic cancer risk in the European Prospective Investigation into Cancer and Nutrition. , 2011, European journal of cancer.

[25]  C. Koumenis,et al.  19-nor-1α,25-Dihydroxyvitamin D2 (Paricalcitol) inhibits the proliferation of human pancreatic cancer cells in vitro and in vivo , 2008, Cancer biology & therapy.

[26]  C. Petitclerc,et al.  International comparisons of nutrition and mortality from pancreatic cancer. , 1991, Cancer detection and prevention.

[27]  K. Dodd,et al.  Folate intake post‐folic acid grain fortification and pancreatic cancer risk in the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial , 2010, The American journal of clinical nutrition.

[28]  Jun Liu,et al.  Diabetes mellitus and risk of pancreatic cancer: A meta-analysis of cohort studies. , 2011, European journal of cancer.

[29]  R. Hayes,et al.  Long-term Variation in Serum 25-Hydroxyvitamin D Concentration among Participants in the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial , 2010, Cancer Epidemiology, Biomarkers & Prevention.

[30]  S. López,et al.  Distinctive postprandial modulation of beta cell function and insulin sensitivity by dietary fats: monounsaturated compared with saturated fatty acids. , 2008, The American journal of clinical nutrition.

[31]  E. Rimm,et al.  A prospective study of folate intake and the risk of pancreatic cancer in men and women. , 2004, American journal of epidemiology.

[32]  廣畑 富雄,et al.  Food, Nutrition, Physical Activity, and the Prevention of Cancer: a Global Perspective , 2007 .

[33]  D. Albanes,et al.  Dietary and other methyl-group availability factors and pancreatic cancer risk in a cohort of male smokers. , 2001, American journal of epidemiology.

[34]  W. Willett,et al.  A randomized trial on folic acid supplementation and risk of recurrent colorectal adenoma. , 2009, The American journal of clinical nutrition.

[35]  Elizabeth L. Barry,et al.  Folic acid for the prevention of colorectal adenomas: a randomized clinical trial. , 2007, JAMA.

[36]  A. Saha,et al.  Anti-growth effect of 1,25-dihydroxyvitamin D3-3-bromoacetate alone or in combination with 5-amino-imidazole-4-carboxamide-1-beta-4-ribofuranoside in pancreatic cancer cells. , 2010, Anticancer research.

[37]  E. Holly,et al.  Intake of fatty acids and antioxidants and pancreatic cancer in a large population‐based case‐control study in the San Francisco Bay Area , 2010, International journal of cancer.

[38]  Brian E Henderson,et al.  Meat and fat intake as risk factors for pancreatic cancer: the multiethnic cohort study. , 2005, Journal of the National Cancer Institute.

[39]  R. Hayes,et al.  Circulating 25-Hydroxyvitamin D and Risk of Pancreatic Cancer , 2010, American journal of epidemiology.

[40]  I. Rosenberg,et al.  A Temporal Association between Folic Acid Fortification and an Increase in Colorectal Cancer Rates May Be Illuminating Important Biological Principles: A Hypothesis , 2007, Cancer Epidemiology Biomarkers & Prevention.

[41]  W. Willett,et al.  Vitamin D Intake and the Risk for Pancreatic Cancer in Two Cohort Studies , 2006, Cancer Epidemiology Biomarkers & Prevention.

[42]  B. M. Rasmussen,et al.  Substituting dietary saturated for monounsaturated fat impairs insulin sensitivity in healthy men and women: The KANWU study , 2001, Diabetologia.

[43]  M. Okada,et al.  Geographical distribution for malignant neoplasm of the pancreas in relation to selected climatic factors in Japan , 2007, International journal of health geographics.

[44]  Patrick Maisonneuve,et al.  Epidemiology of pancreatic cancer: an overview , 2009, Nature Reviews Gastroenterology &Hepatology.

[45]  JoAnn E. Manson,et al.  The 2011 Report on Dietary Reference Intakes for Calcium and Vitamin D from the Institute of Medicine: What Clinicians Need to Know , 2010, The Journal of clinical endocrinology and metabolism.

[46]  D. Albanes,et al.  Prospective study of diet and pancreatic cancer in male smokers. , 2002, American journal of epidemiology.

[47]  T. Fahey,et al.  Bile acids induce cyclooxygenase-2 expression in human pancreatic cancer cell lines. , 2003, Carcinogenesis.

[48]  R. Woutersen,et al.  Dietary fat and carcinogenesis. , 1999, Mutation research.

[49]  S. Larsson,et al.  Folate intake, MTHFR polymorphisms, and risk of esophageal, gastric, and pancreatic cancer: a meta-analysis. , 2006, Gastroenterology.

[50]  R. Hayes,et al.  American Journal of Epidemiology Original Contribution Circulating 25-hydroxyvitamin D and Risk of Kidney Cancer Cohort Consortium Vitamin D Pooling Project of Rarer Cancers , 2022 .

[51]  D. Krewski,et al.  Specific fatty acid intake and the risk of pancreatic cancer in Canada , 2005, British Journal of Cancer.

[52]  J. Mason,et al.  Effects of dietary folate on intestinal tumorigenesis in the apcMin mouse. , 2000, Cancer research.

[53]  Young-In Kim Role of folate in colon cancer development and progression. , 2003, The Journal of nutrition.

[54]  D. Albanes,et al.  Insulin, glucose, insulin resistance, and pancreatic cancer in male smokers. , 2005, JAMA.

[55]  B. Blumberg,et al.  The steroid and xenobiotic receptor (SXR), beyond xenobiotic metabolism , 2009, Nuclear receptor signaling.

[56]  G. Block,et al.  The Effect of Folate Fortification of Cereal-Grain Products on Blood Folate Status, Dietary Folate Intake, and Dietary Folate Sources among Adult Non-Supplement Users in the United States , 2005, Journal of the American College of Nutrition.

[57]  K. Anderson,et al.  Physical Activity, Diet, and Pancreatic Cancer: A Population-Based, Case-Control Study in Minnesota , 2009, Nutrition and cancer.

[58]  H. Berkel,et al.  Animal fat consumption and pancreatic cancer incidence: evidence of interaction with cigarette smoking. , 2005, Annals of epidemiology.

[59]  R. Goldbohm,et al.  Dietary Folate and Folate Vitamers and the Risk of Pancreatic Cancer in the Netherlands Cohort Study , 2009, Cancer Epidemiology Biomarkers & Prevention.

[60]  M. Stampfer,et al.  Plasma folate, vitamin B6, vitamin B12, and homocysteine and pancreatic cancer risk in four large cohorts. , 2007, Cancer research.

[61]  M. Woodward,et al.  Type-II diabetes and pancreatic cancer: a meta-analysis of 36 studies , 2005, British Journal of Cancer.

[62]  R. Hayes,et al.  Serum vitamin D and risk of pancreatic cancer in the prostate, lung, colorectal, and ovarian screening trial. , 2009, Cancer research.