TY - JOUR
T1 - Energy balance, polymorphisms in the mTOR pathway, and renal cell carcinoma risk
AU - Shu, Xiang
AU - Lin, Jie
AU - Wood, Christopher G.
AU - Tannir, Nizar M.
AU - Wu, Xifeng
N1 - Funding Information:
This work was supported in part by grants from the National Cancer Institute (R01 CA111646, P50 CA070907, R01 CA127219, R01 CA55769, and R03 CA128079).
PY - 2013/3/20
Y1 - 2013/3/20
N2 - Background 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. Methods 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. Results 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. Conclusion Obesity, weight gain, physical activity, and genetic variants in the mTOR pathway may individually and jointly influence susceptibility to RCC.
AB - Background 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. Methods 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. Results 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. Conclusion Obesity, weight gain, physical activity, and genetic variants in the mTOR pathway may individually and jointly influence susceptibility to RCC.
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U2 - 10.1093/jnci/djt005
DO - 10.1093/jnci/djt005
M3 - Article
C2 - 23378641
AN - SCOPUS:84875586535
SN - 0027-8874
VL - 105
SP - 424
EP - 432
JO - Journal of the National Cancer Institute
JF - Journal of the National Cancer Institute
IS - 6
ER -