Department of Epidemiology, Unit 1340, University of Texas MD Anderson Cancer Center, 1155 Pressler Blvd, Houston, TX 77030, USA.
J Natl Cancer Inst. 2013 Mar 20;105(6):424-32. doi: 10.1093/jnci/djt005. Epub 2013 Feb 2.
The interplay between obesity, physical activity, weight gain, and genetic variants in the mTOR pathway has not been studied in renal cell carcinoma (RCC). We examined the associations between obesity, weight gain, physical activity, and RCC risk. We also analyzed whether genetic variants in the mTOR pathway could modify the association.
Incident RCC case subjects and healthy control subjects were recruited from the University of Texas MD Anderson Cancer Center in Houston, Texas. Case subjects and control subjects were frequency matched. Epidemiologic data were collected by in-person interview. One hundred ninety single nucleotide polymorphisms (SNPs) from 22 genes in the mTOR pathway were extracted from previous genome-wide association studies. Logistic regression and regression spline were performed to obtain odds ratios (ORs). All statistical tests were two-sided.
A total of 577 non-Hispanic white case subjects and 593 healthy control subjects were included. Obesity at age 20 years (OR = 1.92, 95% confidence interval [CI] = 1.05 to 3.50; P = .03) and age 40 years (OR = 2.03, 95% CI = 1.38 to 2.98; P < .001) and moderate (OR = 1.46, 95% CI = 1.02 to 2.09; P = .04) and massive weight gain (OR = 1.62, 95% CI = 1.10 to 2.39; P = .01) from age 20 to 40 years were each statistically significantly associated with increased RCC risk. Low physical activity was associated with a 4.08-fold increased risk. Among 190 SNPs in the mTOR pathway, six SNPs located in the AKT3 gene were statistically significantly associated with increased risk, and those with three or more unfavorable genotypes had a 1.72-fold increased risk of RCC.
Obesity, weight gain, physical activity, and genetic variants in the mTOR pathway may individually and jointly influence susceptibility to RCC.
肥胖、体力活动、体重增加和 mTOR 通路中的遗传变异之间的相互作用尚未在肾细胞癌 (RCC) 中进行研究。我们检查了肥胖、体重增加、体力活动与 RCC 风险之间的关联。我们还分析了 mTOR 通路中的遗传变异是否可以改变这种关联。
来自德克萨斯州休斯顿的德克萨斯大学 MD 安德森癌症中心的 RCC 病例和健康对照被招募。病例和对照按频率匹配。通过面对面访谈收集流行病学数据。从之前的全基因组关联研究中提取了 mTOR 通路中的 22 个基因中的 190 个单核苷酸多态性 (SNP)。使用逻辑回归和回归样条获得比值比 (OR)。所有统计检验均为双侧。
共纳入 577 名非西班牙裔白人病例和 593 名健康对照。20 岁时肥胖 (OR = 1.92，95%置信区间 [CI] = 1.05 至 3.50；P =.03) 和 40 岁时肥胖 (OR = 2.03，95% CI = 1.38 至 2.98；P <.001) 以及从 20 岁到 40 岁之间的中度 (OR = 1.46，95% CI = 1.02 至 2.09；P =.04) 和大量体重增加 (OR = 1.62，95% CI = 1.10 至 2.39；P =.01) 均与 RCC 风险增加有统计学意义。体力活动不足与风险增加 4.08 倍相关。在 mTOR 通路中的 190 个 SNP 中，位于 AKT3 基因中的 6 个 SNP 与增加的风险有统计学意义，并且具有三个或更多不利基因型的患者患 RCC 的风险增加 1.72 倍。
肥胖、体重增加、体力活动和 mTOR 通路中的遗传变异可能单独和共同影响 RCC 的易感性。
