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Body Mass Index and Obesity- and Diabetes-Associated Genotypes and Risk for Pancreatic Cancer
- Source :
- Cancer Epidemiology, Biomarkers & Prevention. 20:779-792
- Publication Year :
- 2011
- Publisher :
- American Association for Cancer Research (AACR), 2011.
-
Abstract
- 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/m2 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. Cancer Epidemiol Biomarkers Prev; 20(5); 779–92. ©2011 AACR.
- Subjects :
- Male
Oncology
medicine.medical_specialty
Pancreatic disease
Genotype
Epidemiology
Alpha-Ketoglutarate-Dependent Dioxygenase FTO
Receptors, Cytoplasmic and Nuclear
AMP-Activated Protein Kinases
Adenocarcinoma
ADIPOQ Gene
Polymorphism, Single Nucleotide
FTO gene
Article
Body Mass Index
Diabetes Complications
Risk Factors
Pancreatic cancer
Internal medicine
Humans
Medicine
Obesity
Aged
business.industry
Proteins
Cancer
Middle Aged
Overweight
medicine.disease
PPAR gamma
Pancreatic Neoplasms
Endocrinology
Diabetes Mellitus, Type 2
Case-Control Studies
Female
business
Body mass index
Subjects
Details
- ISSN :
- 15387755 and 10559965
- Volume :
- 20
- Database :
- OpenAIRE
- Journal :
- Cancer Epidemiology, Biomarkers & Prevention
- Accession number :
- edsair.doi.dedup.....d2285b2201a5413a20835552e91aff3d