title: Energy balance, polymorphisms in the mTOR pathway, and renal cell carcinoma risk.
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.
  
  
  CONCLUSIONS
  Obesity, weight gain, physical activity, and genetic variants in the mTOR pathway may individually and jointly influence susceptibility to RCC.
authors: Department of Epidemiology, Unit 1340, University of Texas MD Anderson Cancer Center, 1155 Pressler Blvd, Houston, TX 77030, USA.
authors: Xiang
authors: X
authors: Shu
authors: Jie
authors: J
authors: Lin
authors: Christopher G
authors: CG
authors: Wood
authors: Nizar M
authors: NM
authors: Tannir
authors: Xifeng
authors: X
authors: Wu
mesh_terms: D000328:Adult; D000368:Aged; D015992:Body Mass Index; D002292:Carcinoma, Renal Cell / Q000209:etiology* / Q000235:genetics / Q000378:metabolism; D016022:Case-Control Studies; D002149:Energy Intake; D004734:Energy Metabolism; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D007680:Kidney Neoplasms / Q000209:etiology* / Q000235:genetics / Q000378:metabolism; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D009043:Motor Activity; D015999:Multivariate Analysis; D009765:Obesity / Q000150:complications*; D016017:Odds Ratio; D020641:Polymorphism, Single Nucleotide; D012307:Risk Factors; D015398:Signal Transduction / Q000235:genetics; D058570:TOR Serine-Threonine Kinases / Q000235:genetics* / Q000378:metabolism; D013781:Texas; D015430:Weight Gain
chemical_list: C546842:MTOR protein, human; D058570:TOR Serine-Threonine Kinases
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