Department of Epidemiology & Population Health, Albert Einstein College of Medicine, 1300 Morris Park Avenue, Bronx, New York, NY 10461, USA.
Cancer Epidemiol Biomarkers Prev. 2010 Aug;19(8):2106-9. doi: 10.1158/1055-9965.EPI-10-0515. Epub 2010 Jul 20.
Obesity and diabetes are known risk factors for endometrial cancer; thus, the genetic risk factors of these phenotypes might also be associated with endometrial cancer risk. To evaluate this hypothesis, we genotyped tag-single nucleotide polymorphisms (SNP) and candidate SNPs in FTO and HHEX in a primary set of 417 endometrial cancer cases and 406 population-based controls, and validated significant findings in a replication set of approximately 2,347 cases and 3,140 controls from three additional studies.
We genotyped 189 tagSNPs in FTO (including rs8050136) and five tagSNPs in HHEX (including rs1111875) in the primary set and one SNP each in FTO (rs12927155) and HHEX (rs1111875) in the validation set. Per allele odds ratios (OR) and 95% confidence intervals (CI) were calculated to estimate the association between the genotypes of each SNPs (as an ordinal variable) and endometrial cancer risk using unconditional logistic regression models, controlling for age and site.
In the primary study, the most significant finding in FTO was rs12927155 (OR, 1.56; 95% CI, 1.21-2.01; P = 5.8 x 10(-4)), and in HHEX, it was rs1111875 (OR, 0.80; 95% CI, 0.66-0.97; P = 0.026). In the validation studies, the pooled per allele OR, adjusted for age and study for FTO, was rs12927155 (OR, 0.94; 95% CI, 0.83-1.06; P = 0.29), whereas for HHEX, it was rs1111875 (OR, 1.00; 95% CI, 0.92-1.10; P = 0.96).
Our data indicate that common genetic variants in two genes previously related to obesity (FTO) and diabetes (HHEX) by genome-wide association scans were not associated with endometrial cancer risk.
Polymorphisms in FTO and HHEX are unlikely to have large effects on endometrial cancer risk but may have weaker effects.
肥胖和糖尿病是子宫内膜癌的已知风险因素；因此，这些表型的遗传风险因素也可能与子宫内膜癌的风险相关。为了验证这一假设，我们在一个由 417 名子宫内膜癌病例和 406 名基于人群的对照组组成的主要研究组中对 FTO 和 HHEX 中的标签单核苷酸多态性 (SNP) 和候选 SNP 进行了基因分型，并在来自三个额外研究的约 2347 例病例和 3140 例对照组的复制研究组中验证了显著发现。
我们在主要研究组中对 FTO（包括 rs8050136）中的 189 个标签 SNP 和 HHEX（包括 rs1111875）中的 5 个标签 SNP 进行了基因分型，并在验证研究组中对 FTO（rs12927155）和 HHEX（rs1111875）中的每个 SNP 进行了基因分型。使用无条件逻辑回归模型，根据年龄和部位，计算每个 SNP（作为有序变量）基因型与子宫内膜癌风险之间的等位基因比值 (OR) 和 95%置信区间 (CI)，以估计基因型与子宫内膜癌风险之间的关联。
在主要研究中，FTO 中最显著的发现是 rs12927155（OR，1.56；95%CI，1.21-2.01；P = 5.8 x 10(-4)），而在 HHEX 中，是 rs1111875（OR，0.80；95%CI，0.66-0.97；P = 0.026）。在验证研究中，经年龄和研究调整后的 FTO 每个等位基因的 OR 总和为 rs12927155（OR，0.94；95%CI，0.83-1.06；P = 0.29），而对于 HHEX，是 rs1111875（OR，1.00；95%CI，0.92-1.10；P = 0.96）。
我们的数据表明，全基因组关联扫描先前与肥胖（FTO）和糖尿病（HHEX）相关的两个基因中的常见遗传变异与子宫内膜癌风险无关。
FTO 和 HHEX 中的多态性不太可能对子宫内膜癌风险有较大影响，但可能有较弱的影响。
