Year: 2013
Type: article
Study design: Observational Study
Abstract: 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.
DOI: 10.1093/jnci/djt005
Institution: The University of Texas MD Anderson Cancer Center
Language: English
Topic: Cancer Risks and Factors
Subfield: Oncology
Field: Medicine
Domain: Health Sciences
Open Access status: bronze
Funder: National Cancer Institute
Awards: Inflammation Genes and Lung Cancer Risk, G1135378803, G1394878971, G1767672275, Genetic Polymorphisms in TRAIL Pathway as Susceptibility Markers for Lung Cancer, Molecular pathways linking obesity and RCC tumorigenesis (PQ1), Lung Cancer Chemoradiation: Predictors of Survival, Adenocarcinoma of the Lung: role of NNK susceptibility, Targeting Lung Cancer Vulnerabilities, DNA repair, Cell cycle Checkpoints and Apoptosis and Bladder Cancer Risk, Cancer Center Support Grant
OpenAlex ID: W2150623476