title: Body mass index and obesity- and diabetes-associated genotypes and risk for pancreatic cancer.
abstract: BACKGROUND
  The genetic factors predisposing individuals with obesity or diabetes to pancreatic cancer have not been identified.
  
  
  OBJECTIVE
  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.
  
  
  CONCLUSIONS
  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.
  
  
  CONCLUSIONS
  The discovery of genetic factors modifying the risk of pancreatic cancer may help to identify high-risk individuals for prevention efforts.
authors.affiliation: Department of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
authors.forename: Hongwei
authors.initials: H
authors.lastname: Tang
authors.forename: Xiaoqun
authors.initials: X
authors.lastname: Dong
authors.forename: Manal
authors.initials: M
authors.lastname: Hassan
authors.forename: James L
authors.initials: JL
authors.lastname: Abbruzzese
authors.forename: Donghui
authors.initials: D
authors.lastname: Li
mesh_terms: D055372:AMP-Activated Protein Kinases / Q000235:genetics; D000230:Adenocarcinoma / Q000209:etiology*; D000368:Aged; D000071516:Alpha-Ketoglutarate-Dependent Dioxygenase FTO; D015992:Body Mass Index; D016022:Case-Control Studies; D048909:Diabetes Complications / Q000235:genetics*; D003924:Diabetes Mellitus, Type 2 / Q000235:genetics*; D005260:Female; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D009765:Obesity / Q000235:genetics*; D050177:Overweight / Q000235:genetics*; D047495:PPAR gamma / Q000235:genetics; D010190:Pancreatic Neoplasms / Q000209:etiology*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D011506:Proteins / Q000235:genetics; D018160:Receptors, Cytoplasmic and Nuclear / Q000235:genetics; D012307:Risk Factors
chemical_list: C082631:NR5A2 protein, human; D047495:PPAR gamma; D011506:Proteins; D018160:Receptors, Cytoplasmic and Nuclear; D000071516:Alpha-Ketoglutarate-Dependent Dioxygenase FTO; C526492:FTO protein, human; C526181:PRKAA2 protein, human; C526182:PRKAB1 protein, human; C526183:PRKAB2 protein, human; D055372:AMP-Activated Protein Kinases