title: Association between Variants in Atopy-Related Immunologic Candidate Genes and Pancreatic Cancer Risk.
abstract: BACKGROUND
  Many epidemiology studies report that atopic conditions such as allergies are associated with reduced pancreas cancer risk. The reason for this relationship is not yet understood. This is the first study to comprehensively evaluate the association between variants in atopy-related candidate genes and pancreatic cancer risk.
  
  
  METHODS
  A population-based case-control study of pancreas cancer cases diagnosed during 2011-2012 (via Ontario Cancer Registry), and controls recruited using random digit dialing utilized DNA from 179 cases and 566 controls. Following an exhaustive literature review, SNPs in 180 candidate genes were pre-screened using dbGaP pancreas cancer GWAS data; 147 SNPs in 56 allergy-related immunologic genes were retained and genotyped. Logistic regression was used to estimate age-adjusted odd ratio (AOR) for each variant and false discovery rate was used to adjust Wald p-values for multiple testing. Subsequently, a risk allele score was derived based on statistically significant variants.
  
  
  RESULTS
  18 SNPs in 14 candidate genes (CSF2, DENND1B, DPP10, FLG, IL13, IL13RA2, LRP1B, NOD1, NPSR1, ORMDL3, RORA, STAT4, TLR6, TRA) were significantly associated with pancreas cancer risk. After adjustment for multiple comparisons, two LRP1B SNPs remained statistically significant; for example, LRP1B rs1449477 (AA vs. CC: AOR=0.37, 95% CI: 0.22-0.62; p (adjusted)=0.04). Furthermore, the risk allele score was associated with a significant reduction in pancreas cancer risk (p=0.0007).
  
  
  CONCLUSIONS
  Preliminary findings suggest certain atopy-related variants may be associated with pancreas cancer risk. Further studies are needed to replicate this, and to elucidate the biology behind the growing body of epidemiologic evidence suggesting allergies may reduce pancreatic cancer risk.
authors.affiliation: Prevention and Cancer Control, Cancer Care Ontario, Toronto, ON M5G 2L7, Canada; Dalla Lana School of Public Health, University of Toronto, Toronto, ON M5T 3M7, Canada.
authors.forename: Michelle
authors.initials: M
authors.lastname: Cotterchio
authors.affiliation: Prevention and Cancer Control, Cancer Care Ontario, Toronto, ON M5G 2L7, Canada.
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Lowcock
authors.affiliation: Prevention and Cancer Control, Cancer Care Ontario, Toronto, ON M5G 2L7, Canada.
authors.forename: Zoe
authors.initials: Z
authors.lastname: Bider-Canfield
authors.affiliation: Ontario Institute for Cancer Research, Toronto, ON M5G 0A3, Canada.
authors.forename: Mathieu
authors.initials: M
authors.lastname: Lemire
authors.affiliation: Lady Davis Institute for Medical Research, Jewish General Hospital, Montreal, QC H3T 1E2, Canada.
authors.forename: Celia
authors.initials: C
authors.lastname: Greenwood
authors.affiliation: Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, Toronto, ON M5G 1X5, Canada; Division of General Surgery, Toronto General Hospital, Toronto, ON M5G 2C4, Canada.
authors.forename: Steven
authors.initials: S
authors.lastname: Gallinger
authors.affiliation: Ontario Institute for Cancer Research, Toronto, ON M5G 0A3, Canada; Department of Molecular Genetics, University of Toronto, Toronto, ON M5S 1A1, Canada.
authors.forename: Thomas
authors.initials: T
authors.lastname: Hudson
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D016022:Case-Control Studies; D005260:Female; D000091344:Filaggrin Proteins; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D005838:Genotype; D006801:Humans; D006969:Hypersensitivity, Immediate / Q000235:genetics* / Q000276:immunology; D008297:Male; D008875:Middle Aged; D009864:Ontario; D010179:Pancreas / Q000276:immunology; D010190:Pancreatic Neoplasms / Q000453:epidemiology / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D011159:Population Surveillance; D012307:Risk Factors