TY - JOUR
T1 - Potential susceptibility loci identified for renal cell carcinoma by targeting obesity-related genes
AU - Shu, Xiang
AU - Purdue, Mark P.
AU - Ye, Yuanqing
AU - Tu, Huakang
AU - Wood, Christopher G.
AU - Tannir, Nizar M.
AU - Wang, Zhaoming
AU - Albanes, Demetrius
AU - Gapstur, Susan M.
AU - Stevens, Victoria L.
AU - Rothman, Nathaniel
AU - Chanock, Stephen J.
AU - Wu, Xifeng
N1 - Funding Information:
This work was supported in part by the NIH (grant R01 CA170298 to X. Wu), and the Center for Translational and Public Health Genomics, Duncan Family Institute for Cancer Prevention, The University of Texas MD Anderson Cancer Center. The NCI RCC GWAS was supported by the Intramural Research Program of the NIH, NCI.
Publisher Copyright:
© 2017 American Association for Cancer Research.
PY - 2017/9/1
Y1 - 2017/9/1
N2 - 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 bothMDARCC GWAS and NCI RCC GWAS were subsequently evaluated in MDA RCC OncoArray. In the overall meta-Analysis, significant (P < 0.05) associations withRCC 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.
AB - 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 bothMDARCC GWAS and NCI RCC GWAS were subsequently evaluated in MDA RCC OncoArray. In the overall meta-Analysis, significant (P < 0.05) associations withRCC 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.
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U2 - 10.1158/1055-9965.EPI-17-0141
DO - 10.1158/1055-9965.EPI-17-0141
M3 - Article
C2 - 28626070
AN - SCOPUS:85028917158
SN - 1055-9965
VL - 26
SP - 1436
EP - 1442
JO - Cancer Epidemiology Biomarkers and Prevention
JF - Cancer Epidemiology Biomarkers and Prevention
IS - 9
ER -