Association between the ERCC2 Asp312Asn polymorphism and risk of cancer

// Feifan Xiao 1, 2, * , Jian Pu 3, * , Qiongxian Wen 4, * , Qin Huang 5, * , Qinle Zhang 6, * , Birong Huang 1, 2 , Shanshan Huang 1, 2 , Aihua Lan 1, 2 , Yuening Zhang 1 , Jiatong Li 1 , Dong Zhao 1 , Jing Shen 1 , Huayu Wu 7 , Yan He 8 , Hongtao Li 1 and Xiaoli Yang 1 1 Medical Scientific Research Center, Guangxi Medical University, Nanning, Guangxi, P.R. China 2 First Clinical Academy, Guangxi Medical University, Nanning, Guangxi, P.R. China 3 Liver and Gall Surgical Department, The Affiliated Hospital of Youjiang Medical College for Nationalities, Baise, Guangxi, P.R. China 4 School of Nursing, The Second Affiliated Hospital of Guilin Medical University, Guilin, Guangxi, P.R. China 5 Guangxi Key Laboratory of Chemistry and Engineering of Forest Products, Guangxi University for Nationalities, Nanning, Guangxi, P.R. China 6 Genetic and Metabolic Central Laboratory, The Maternal and Children Health Hospital of Guangxi, Nanning, Guangxi, P.R. China 7 Department of Cell Biology and Genetics, School of Premedical Sciences, Guangxi Medical University, Nanning, Guangxi, P.R. China 8 Geriatrics Cardiology Division, First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, P.R. China * These authors have contributed equally to this work and should be considered as co-first authors Correspondence to: Xiaoli Yang, email: cncsyxl@126.com Keywords: ERCC2 Asp312Asn, polymorphism, cancer, meta-analysis, trial sequence analysis Received: September 23, 2016 Accepted: April 04, 2017 Published: April 20, 2017 ABSTRACT Cancer is the leading cause of death in economically developed countries and the second leading cause of death in developing countries. The relationship between genetic polymorphisms and the risk of cancers has been widely researched. Excision repair cross-complementing group 2 ( ERCC2 ) gene plays important roles in the nucleotide excision repair pathway. There is contrasting evidence on the association between the ERCC2 Asp312Asn polymorphism and the risk of cancer. We conducted a comprehensive meta-analysis in order to assess the correlation between these factors. We searched the PubMed, EMBASE, Science Direct, Web of Science, and CNKI databases for studies published from January 1, 2005 to January 1, 2016. Finally, 86 articles with 38,848 cases and 48,928 controls were included in the analysis. The overall analysis suggested a significant association between the ERCC2 Asp312Asn polymorphism and cancer risk. Furthermore, control source, ethnicity, genotyping method, and cancer type were used for subgroup analysis. The result of a trial sequential analysis indicated that the cumulative evidence is adequate; hence, further trials were unnecessary in the overall analysis for homozygote comparison. In summary, our results suggested that ERCC2 Asp312Asn polymorphism is associated with increased cancer risk. A significantly increased cancer risk was observed in Asian populations, but not in Caucasian populations. Furthermore, the ERCC2 Asp312Asn polymorphism is associated with bladder, esophageal, and gastric cancers, but not with breast, head and neck, lung, prostate, and skin cancers, and non-Hodgkin lymphoma. Further multi-center, well-designed studies are required to validate our results.