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Cancer Epidemiol Biomarkers Prev. 2017 Sep;26(9):1436-1442. doi: 10.1158/1055-9965.EPI-17-0141. Epub 2017 Jun 16.

Potential Susceptibility Loci Identified for Renal Cell Carcinoma by Targeting Obesity-Related Genes.

Author information

1
Department of Epidemiology, The University of Texas MD Anderson Cancer Center, Houston, Texas.
2
Division of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville, Maryland.
3
Department of Urology, The University of Texas MD Anderson Cancer Center, Houston, Texas.
4
Department of Genitourinary Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas.
5
Epidemiology Research Program, American Cancer Society, Atlanta, Georgia.
6
Department of Epidemiology, The University of Texas MD Anderson Cancer Center, Houston, Texas. xwu@mdanderson.org.

Abstract

Background: Obesity is an established risk factor for renal cell carcinoma (RCC). Although genome-wide association studies (GWAS) of RCC have identified several susceptibility loci, additional variants might be missed due to the highly conservative selection.Methods: We conducted a multiphase study utilizing three independent genome-wide scans at MD Anderson Cancer Center (MDA RCC GWAS and MDA RCC OncoArray) and National Cancer Institute (NCI RCC GWAS), which consisted of a total of 3,530 cases and 5,714 controls, to investigate genetic variations in obesity-related genes and RCC risk.Results: In the discovery phase, 32,946 SNPs located at ±10 kb of 2,001 obesity-related genes were extracted from MDA RCC GWAS and analyzed using multivariable logistic regression. Proxies (R2 > 0.8) were searched or imputation was performed if SNPs were not directly genotyped in the validation sets. Twenty-one SNPs with P < 0.05 in both MDA RCC GWAS and NCI RCC GWAS were subsequently evaluated in MDA RCC OncoArray. In the overall meta-analysis, significant (P < 0.05) associations with RCC risk were observed for SNP mapping to IL1RAPL2 [rs10521506-G: ORmeta = 0.87 (0.81-0.93), Pmeta = 2.33 × 10-5], PLIN2 [rs2229536-A: ORmeta = 0.87 (0.81-0.93), Pmeta = 2.33 × 10-5], SMAD3 [rs4601989-A: ORmeta = 0.86 (0.80-0.93), Pmeta = 2.71 × 10-4], MED13L [rs10850596-A: ORmeta = 1.14 (1.07-1.23), Pmeta = 1.50 × 10-4], and TSC1 [rs3761840-G: ORmeta = 0.90 (0.85-0.97), Pmeta = 2.47 × 10-3]. We did not observe any significant cis-expression quantitative trait loci effect for these SNPs in the TCGA KIRC data.Conclusions: Taken together, we found that genetic variation of obesity-related genes could influence RCC susceptibility.Impact: The five identified loci may provide new insights into disease etiology that reveal importance of obesity-related genes in RCC development. Cancer Epidemiol Biomarkers Prev; 26(9); 1436-42. ©2017 AACR.

PMID:
28626070
PMCID:
PMC5581698
DOI:
10.1158/1055-9965.EPI-17-0141
[Indexed for MEDLINE]
Free PMC Article

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