TY - JOUR
T1 - Body mass index and obesity- and diabetes-associated genotypes and risk for pancreatic cancer
AU - Tang, Hongwei
AU - Dong, Xiaoqun
AU - Hassan, Manal
AU - Abbruzzese, James L.
AU - Li, Donghui
PY - 2011/5
Y1 - 2011/5
N2 - 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; Pinteraction = 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 PPARg 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.
AB - 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; Pinteraction = 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 PPARg 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.
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U2 - 10.1158/1055-9965.EPI-10-0845
DO - 10.1158/1055-9965.EPI-10-0845
M3 - Article
C2 - 21357378
AN - SCOPUS:79955752416
SN - 1055-9965
VL - 20
SP - 779
EP - 792
JO - Cancer Epidemiology Biomarkers and Prevention
JF - Cancer Epidemiology Biomarkers and Prevention
IS - 5
ER -