title: FTO polymorphisms are associated with adult body mass index (BMI) and colorectal adenomas in African-Americans.
abstract: Obesity is a known risk factor for colon cancer and higher body mass index (BMI) has been associated with colorectal adenomas, which are precursor lesions to most colorectal cancers. Polymorphisms in the fat-mass and obesity-associated (FTO) gene have been associated with BMI and larger effects in older versus younger children have been reported. However, no studies have examined associations between FTO polymorphisms, BMI throughout adulthood and colorectal adenomas. Therefore, we evaluated associations between FTO polymorphisms (rs1421085, rs17817449, rs8050136, rs9939609, rs8044769), adult BMI (at recruitment, 50s, 40s, 30s, 20s age decades) and colorectal adenomas in 759 Caucasians and 469 African-Americans. We found that the highest versus the lowest BMI tertile at recruitment [odds ratio (OR) = 1.82; 95% confidence interval (CI): 1.07-2.16] and in the 30s (OR = 1.50; 95% CI: 1.04-2.15) was associated with higher adenoma risk. Stratification by ethnicity revealed that these associations only remained significant in Caucasians. We found that, in Caucasians, having two versus no copies of the variant allele in rs17817449, rs8050136 and rs9939609, which are all in strong linkage disequilibrium, was associated with higher BMI in the 30s and 40s but none of the polymorphisms were associated with adenomas. In African-Americans, having one or two copies of the variant in rs17817449 (OR = 0.61; 95% CI: 0.39-0.95) and rs8050136 (OR = 0.59; 95% CI: 0.38-0.93) was associated with colorectal adenomas and, having two variant copies in rs17817449 and rs8050136 was associated with higher BMI at recruitment and in the 40s, respectively. Our results are consistent with prior studies and show for the first time that FTO polymorphisms are associated with colorectal adenomas in African-Americans.
authors.affiliation: Department of Epidemiology and Biostatistics, Case Comprehensive Cancer Center, Case Western Reserve University, Cleveland, OH 44106-7281, USA. nln@case.edu
authors.forename: Nora L
authors.initials: NL
authors.lastname: Nock
authors.forename: Sarah J
authors.initials: SJ
authors.lastname: Plummer
authors.forename: Cheryl L
authors.initials: CL
authors.lastname: Thompson
authors.forename: Graham
authors.initials: G
authors.lastname: Casey
authors.forename: Li
authors.initials: L
authors.lastname: Li
mesh_terms: D000236:Adenoma / Q000208:ethnology / Q000235:genetics*; D000328:Adult; D001741:Black or African American / Q000235:genetics*; D000071516:Alpha-Ketoglutarate-Dependent Dioxygenase FTO; D015992:Body Mass Index; D016022:Case-Control Studies; D003106:Colon / Q000378:metabolism / Q000473:pathology; D015179:Colorectal Neoplasms / Q000208:ethnology / Q000235:genetics*; D004273:DNA, Neoplasm / Q000235:genetics; D005260:Female; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D009765:Obesity / Q000235:genetics; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic / Q000235:genetics*; D011379:Prognosis; D011506:Proteins / Q000235:genetics*; D012007:Rectum / Q000378:metabolism / Q000473:pathology; D012307:Risk Factors; D015996:Survival Rate; D014481:United States; D044465:White People / Q000235:genetics; D055815:Young Adult
chemical_list: D004273:DNA, Neoplasm; D011506:Proteins; D000071516:Alpha-Ketoglutarate-Dependent Dioxygenase FTO; C526492:FTO protein, human