TY - JOUR

T1 - Identification of an SCLC susceptibility rs7963551 genetic polymorphism in a previously GWAS-identified 12p13.33 RAD52 lung cancer risk locus in the Chinese population

AU - Han, Sichong

AU - Gao, Feng

AU - Yang, Wenjun

AU - Ren, Yanli

AU - Liang, Xue

AU - Xiong, Xiangyu

AU - Pan, Wenting

AU - Zhou, Liqing

AU - Zhou, Changchun

AU - Ma, Fei

AU - Yang, Ming

PY - 2015

Y1 - 2015

N2 - As a well-known DNA repair gene, RAD52 plays an essential role in homologous recombination repair of double strand break, maintenance of genomic stability and prevention of cell malignant transformation. Previous genome-wide association studies (GWASs) have identified common genetic variants at 12p13.33 RAD52 locus associated with lung cancer risk in Caucasians. However, little or nothing has been known about the RAD52 single nucleotide polymorphisms (SNPs) in small cell lung cancer (SCLC) in the Chinese population. As a result, we examined the association between six RAD52 SNPs (rs10849605, rs1051669, rs10774474, rs11571378, rs7963551 and rs6489769) and SCLC susceptibility in Chinese. After 520 SCLC cases and 1040 controls in two independent case-control sets were genotyped, odds ratios (ORs) and 95% confidence intervals (CIs) were calculated by logistic regression. We found that only the RAD52 rs7963551 SNP was significantly associated with SCLC risk among six RAD52 SNPs genotyped. The odds of having the rs7963551 CA genotype in SCLC patients was 0.38 (95% CI = 0.24-0.62, P = 1.1x10(-4)) compared with the CC genotype. Stratified analyses of association between rs7963551 SNP and SCLC risk indicated that the functional polymorphism was only significantly associated with decreased risk among smokers but not nonsmokers. Our results demonstrated that the functional RAD52 rs7963551 SNP contributes to susceptibility to developing SCLC in the Chinese population.

AB - As a well-known DNA repair gene, RAD52 plays an essential role in homologous recombination repair of double strand break, maintenance of genomic stability and prevention of cell malignant transformation. Previous genome-wide association studies (GWASs) have identified common genetic variants at 12p13.33 RAD52 locus associated with lung cancer risk in Caucasians. However, little or nothing has been known about the RAD52 single nucleotide polymorphisms (SNPs) in small cell lung cancer (SCLC) in the Chinese population. As a result, we examined the association between six RAD52 SNPs (rs10849605, rs1051669, rs10774474, rs11571378, rs7963551 and rs6489769) and SCLC susceptibility in Chinese. After 520 SCLC cases and 1040 controls in two independent case-control sets were genotyped, odds ratios (ORs) and 95% confidence intervals (CIs) were calculated by logistic regression. We found that only the RAD52 rs7963551 SNP was significantly associated with SCLC risk among six RAD52 SNPs genotyped. The odds of having the rs7963551 CA genotype in SCLC patients was 0.38 (95% CI = 0.24-0.62, P = 1.1x10(-4)) compared with the CC genotype. Stratified analyses of association between rs7963551 SNP and SCLC risk indicated that the functional polymorphism was only significantly associated with decreased risk among smokers but not nonsmokers. Our results demonstrated that the functional RAD52 rs7963551 SNP contributes to susceptibility to developing SCLC in the Chinese population.

KW - GWAS

KW - RAD52

KW - single nucleotide polymorphism

KW - small cell lung cancer

KW - susceptibility

KW - GENOME-WIDE ASSOCIATION

KW - HOMOLOGOUS RECOMBINATION

KW - SYNTHETICALLY LETHAL

KW - BINDING-SITE

KW - HAN CHINESE

KW - VARIANTS

KW - BRCA2

KW - CARCINOMA

KW - INACTIVATION

KW - CONTRIBUTE

M3 - Journal article

VL - 8

SP - 16528

EP - 16535

JO - International Journal of Clinical and Experimental Medicine

JF - International Journal of Clinical and Experimental Medicine

SN - 1940-5901

IS - 9

ER -