title: Association of obesity-related genetic variants with endometrial cancer risk: a report from the Shanghai Endometrial Cancer Genetics Study.
abstract: Obesity is a well-established risk factor for endometrial cancer, the most common gynecologic malignancy. Recent genome-wide association studies (GWAS) have identified multiple genetic markers for obesity. The authors evaluated the association of obesity-related single nucleotide polymorphisms (SNPs) with endometrial cancer using GWAS data from their recently completed study, the Shanghai Endometrial Cancer Genetics Study, which comprised 832 endometrial cancer cases and 2,049 controls (1996-2005). Thirty-five SNPs previously associated with obesity or body mass index (BMI; weight (kg)/height (m)(2)) at a minimum significance level of ≤5 × 10(-7) in the US National Human Genome Research Institute's GWAS catalog (http://genome.gov/gwastudies) and representing 26 unique loci were evaluated by either direct genotyping or imputation. The authors found that for 22 of the 26 unique loci tested (84.6%), the BMI-associated risk variants were present at a higher frequency in cases than in population controls (P = 0.0003). Multiple regression analysis showed that 9 of 35 BMI-associated variants, representing 7 loci, were significantly associated (P ≤ 0.05) with the risk of endometrial cancer; for all but 1 SNP, the direction of association was consistent with that found for BMI. For consistent SNPs, the allelic odds ratios ranged from 1.15 to 1.29. These 7 loci are in the SEC16B/RASAL, TMEM18, MSRA, SOX6, MTCH2, FTO, and MC4R genes. The associations persisted after adjustment for BMI, suggesting that genetic markers of obesity provide value in addition to BMI in predicting endometrial cancer risk.
authors: Vanderbilt Epidemiology Center, 2525 West End Avenue, Nashville, TN 37203-1738, USA.
authors: Ryan J
authors: RJ
authors: Delahanty
authors: Alicia
authors: A
authors: Beeghly-Fadiel
authors: Yong-Bing
authors: YB
authors: Xiang
authors: Jirong
authors: J
authors: Long
authors: Qiuyin
authors: Q
authors: Cai
authors: Wanqing
authors: W
authors: Wen
authors: Wang-Hong
authors: WH
authors: Xu
authors: Hui
authors: H
authors: Cai
authors: Jing
authors: J
authors: He
authors: Yu-Tang
authors: YT
authors: Gao
authors: Wei
authors: W
authors: Zheng
authors: Xiao Ou
authors: XO
authors: Shu
mesh_terms: D000328:Adult; D000368:Aged; D015992:Body Mass Index; D002681:China / Q000453:epidemiology; D016889:Endometrial Neoplasms / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D005838:Genotype; D015438:Health Behavior; D006801:Humans; D008875:Middle Aged; D009765:Obesity / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D012044:Regression Analysis; D012307:Risk Factors; D012959:Socioeconomic Factors