Body mass index and obesity- and diabetes-associated genotypes and risk for pancreatic cancer.

Journal Article (Journal Article)

BACKGROUND: The genetic factors predisposing individuals with obesity or diabetes to pancreatic cancer have not been identified. AIMS: To investigate the hypothesis that obesity- and diabetes-related genes modify the risk of pancreatic cancer. METHODS: We genotyped 15 single nucleotide polymorphisms of fat mass and obesity-associated (FTO), peroxisome proliferators-activated receptor gamma (PPARγ), nuclear receptor family 5 member 2 (NR5A2), AMPK, and ADIPOQ genes in 1,070 patients with pancreatic cancer and 1,175 cancer-free controls. Information on risk factors was collected by personal interview. Adjusted ORs (AOR) and 95% CIs were calculated using unconditional logistic regression. RESULTS: The PPARγ P12A GG genotype was inversely associated with risk of pancreatic cancer (AOR, 0.21; 95% CI, 0.07-0.62). Three NR5A2 variants that were previously identified in a genome-wide association study were significantly associated with reduced risk of pancreatic cancer, AORs ranging from 0.57 to 0.79. Two FTO gene variants and one ADIPOQ variant were differentially associated with pancreatic cancer according to levels of body mass index (BMI; P(interaction) = 0.0001, 0.0015, and 0.03). For example, the AOR (95% CI) for FTO IVS1-2777AC/AA genotype was 0.72 (0.55-0.96) and 1.54 (1.14-2.09) in participants with a BMI of less than 25 or 25 kg/m(2) or more, respectively. We observed no significant association between AMPK genotype and pancreatic cancer and no genotype interactions with diabetes or smoking. CONCLUSION: Our findings suggest the PPARγ P12A GG genotype and NR5A2 variants may reduce the risk for pancreatic cancer. A positive association of FTO and ADIPOQ gene variants with pancreatic cancer may be limited to persons who are overweight. IMPACT: The discovery of genetic factors modifying the risk of pancreatic cancer may help to identify high-risk individuals for prevention efforts.

Full Text

Duke Authors

Cited Authors

  • Tang, H; Dong, X; Hassan, M; Abbruzzese, JL; Li, D

Published Date

  • May 2011

Published In

Volume / Issue

  • 20 / 5

Start / End Page

  • 779 - 792

PubMed ID

  • 21357378

Pubmed Central ID

  • PMC3089680

Electronic International Standard Serial Number (EISSN)

  • 1538-7755

Digital Object Identifier (DOI)

  • 10.1158/1055-9965.EPI-10-0845


  • eng

Conference Location

  • United States