title: Genetic variants in vitamin d pathway genes and risk of pancreas cancer; results from a population-based case-control study in ontario, Canada.
abstract: Recent studies of 25-hydroxyvitamin D (25(OH)D) levels and pancreas cancer have suggested a potential role of the vitamin D pathway in the etiology of this fatal disease. Variants in vitamin-D related genes are known to affect 25(OH)D levels and function and it is unknown if these variants may influence pancreatic cancer risk. The association between 87 single nucleotide polymorphisms (SNPs) in 11 genes was evaluated within the Ontario Pancreas Cancer Study, a population-based case-control study. Pancreatic cancer cases with pathology confirmed adenocarcinoma were identified from the Ontario Cancer Registry (n = 628) and controls were identified through random digit dialing (n = 1193). Age and sex adjusted odds ratios (OR) and 95% confidence intervals (CI) were estimated by multivariate logistic regression. SNPs in the CYP24A1, CYP2R1, calcium sensing receptor (CASR), vitamin D binding protein (GC), retinoid X receptor-alpha (RXRA) and megalin (LRP2) genes were significantly associated with pancreas cancer risk. For example, pancreas cancer risk was inversely associated with CYP2R1 rs10741657 (AA versus GG, OR = 0.70; 95%CI: 0.51-0.95) and positively with CYP24A1 rs6127119 (TT versus CC. OR = 1.94; 95%CI: 1.28-2.94). None of the associations were statistically significant after adjustment for multiple comparisons. Vitamin D pathway gene variants may be associated with pancreas cancer risk and future studies are needed to understand the possible role of vitamin D in tumorigenesis and may have implications for cancer-prevention strategies.
authors.affiliation: Samuel Lunenfeld Research Institute, Mount Sinai Hospital, Toronto, Ontario, Canada.
authors.forename: Laura N
authors.initials: LN
authors.lastname: Anderson
authors.forename: Michelle
authors.initials: M
authors.lastname: Cotterchio
authors.forename: Julia A
authors.initials: JA
authors.lastname: Knight
authors.forename: Ayelet
authors.initials: A
authors.lastname: Borgida
authors.forename: Steven
authors.initials: S
authors.lastname: Gallinger
authors.forename: Sean P
authors.initials: SP
authors.lastname: Cleary
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002170:Canada; D016022:Case-Control Studies; D053493:Cholestanetriol 26-Monooxygenase / Q000235:genetics; D000072467:Cytochrome P450 Family 2; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics; D006801:Humans; D026561:Low Density Lipoprotein Receptor-Related Protein-2 / Q000235:genetics; D008297:Male; D008875:Middle Aged; D010190:Pancreatic Neoplasms / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D044169:Receptors, Calcium-Sensing / Q000235:genetics; D047490:Retinoid X Receptor alpha / Q000235:genetics; D013250:Steroid Hydroxylases / Q000235:genetics; D014807:Vitamin D / Q000235:genetics / Q000378:metabolism*; D014809:Vitamin D-Binding Protein / Q000235:genetics; D065668:Vitamin D3 24-Hydroxylase; D055815:Young Adult
chemical_list: D026561:Low Density Lipoprotein Receptor-Related Protein-2; D044169:Receptors, Calcium-Sensing; D047490:Retinoid X Receptor alpha; D014809:Vitamin D-Binding Protein; D014807:Vitamin D; D013250:Steroid Hydroxylases; D000072467:Cytochrome P450 Family 2; C506833:CYP2R1 protein, human; D053493:Cholestanetriol 26-Monooxygenase; C585549:CYP24A1 protein, human; D065668:Vitamin D3 24-Hydroxylase