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

Sichong Han; Feng Gao; Wenjun Yang; Yanli Ren; Xue Liang; Xiangyu Xiong; Wenting Pan; Liqing Zhou; Changchun Zhou; Fei Ma; Ming Yang

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

Int J Clin Exp Med. 2015 Sep 15;8(9):16528-35. eCollection 2015.

Authors

Sichong Han¹, Feng Gao², Wenjun Yang³, Yanli Ren¹, Xue Liang¹, Xiangyu Xiong¹, Wenting Pan¹, Liqing Zhou⁴, Changchun Zhou⁵, Fei Ma⁶, Ming Yang¹

Affiliations

¹ State Key Laboratory of Chemical Resource Engineering, Beijing Laboratory of Biomedical Materials, College of Life Science and Technology, Beijing University of Chemical Technology Beijing, China.
² Health Division of Guard Bureau, General Staff Department of Chinese PLA Beijing, China.
³ Oncology Department of Cancer Hospital & Institute, General Hospital, Ningxia Medical University China.
⁴ Clinical Laboratory, Shandong Cancer Hospital, Shandong Academy of Medical Sciences Jinan, Shandong Province, China.
⁵ Department of Radiation Oncology, Huaian No. 2 Hospital Huaian, Jiangsu Province, China.
⁶ Department of Medical Oncology, Cancer Hospital, Chinese Academy of Medical Sciences Beijing, China.

PMID: 26629180
PMCID: PMC4659068

Abstract

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 = 1.1×10(-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.

Keywords: GWAS; RAD52; single nucleotide polymorphism; small cell lung cancer; susceptibility.