Energy Balance, Polymorphisms in the mTOR Pathway, and Renal Cell Carcinoma Risk

• Published in: JNCI : Journal of the National Cancer Institute Vol. 105; no. 6; pp. 424 - 432
• Main Authors: XIANG SHU, JIE LIN, WOOD, Christopher G, TANNIR, Nizar M, XIFENG WU
• Format: Journal Article
• Language: English
• Published: Cary, NC Oxford University Press 20.03.2013; Oxford Publishing Limited (England)
• Subjects: Adult; Aged; Biological and medical sciences; Body Mass Index; Carcinoma, Renal Cell - etiology; Carcinoma, Renal Cell - genetics; Carcinoma, Renal Cell - metabolism; Case-Control Studies; Energy Intake; Energy Metabolism; Female; Genetic Predisposition to Disease; Humans; Kidney cancer; Kidney Neoplasms - etiology; Kidney Neoplasms - genetics; Kidney Neoplasms - metabolism; Kidneys; Logistic Models; Male; Medical research; Medical sciences; Middle Aged; Motor Activity; Multiple tumors. Solid tumors. Tumors in childhood (general aspects); Multivariate Analysis; Nephrology. Urinary tract diseases; Obesity - complications; Odds Ratio; Polymorphism; Polymorphism, Single Nucleotide; Risk Factors; Signal Transduction - genetics; Texas; TOR Serine-Threonine Kinases - genetics; TOR Serine-Threonine Kinases - metabolism; Tumors; Tumors of the urinary system; Weight Gain; Texas; Kidney disease; Urinary system disease; Carcinoma; Genetic variability; Genotype; Risk; Malignant tumor; Energy balance; Cancerology; Kidney cancer; Risk factor; Mammalian target of rapamycin; Grawitz tumor; Cancer; Polymorphism
• ISSN: 0027-8874; 1460-2105
• DOI: 10.1093/jnci/djt005

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.