Lung cancer susceptibility and genetic polymorphism of DNA repair gene XRCC4 in Taiwan

Article type: Research Article

Authors: Hsu, Nan-Yung^{a; d; 1} | Wang, Hwei-Chung^{d; 1} | Wang, Chung-Hsing^{b; d; 1} | Chang, Chia-Lin^d | Chiu, Chang-Fang^{c; d} | Lee, Hong-Zin^d | Tsai, Chia-Wen^d | Bau, Da-Tian^{d; e; *}

Affiliations: [a] Department of Surgery, China Medical University Hospital, Taichung, Taiwan | [b] Department of Pediatrics, China Medical University Hospital, Taichung, Taiwan | [c] Department of Hematology Oncology, China Medical University Hospital, Taichung, Taiwan | [d] Terry Fox Cancer Research Laboratory, China Medical University Hospital, Taichung, Taiwan | [e] Graduate Institute of Chinese Medical Science, China Medical University, Taichung, Taiwan

Correspondence: [*] Corresponding author: Da-Tian Bau, Ph.D., Terry Fox Cancer Research Laboratory, China Medical University Hospital, 2 Yuh-Der Road, Taichung, 404 Taiwan. Tel.: +886422053366 Ext 3312; Fax: +886422053366 Ext 3312; E-mail: [email protected]; [email protected].

Note: [1] These authors contribute equally to this study.

Abstract: Non-homologous end-joining (NHEJ) system is a major route in repairing double strand breaks (DSBs), and is important in maintaining the genome stability. The gene XRCC4 is a central role of the NHEJ system, and it is critical in carcinogenesis. In order to reveal the association between XRCC4 and lung cancer, we recruited 164 lung cancer patients and 649 healthy controls from central Taiwan, investigated seven novel polymorphic variants of XRCC4, includes C-1622T (rs7727691), G-1394T (rs6869366), G-652T (rs2075685), C-571T (rs2075686), intron3 DIP (rs28360071), S247A (rs3734091) and intron7 DIP (rs28360317), and analyzed the association of specific genotype with lung cancer susceptibility. The results showed that the XRCC4 G-1394T is significant in Taiwanese lung cancer and the GT genotype of G-1394T is an obvious risk factor of lung cancer susceptibility (P=0.0049), and the G allele is a risky factor (P=0.0087). As for XRCC4 C-1622T (rs7727691), G-652T (rs2075685), C-571T (rs2075686), intron3 DIP (rs28360071), S247A (rs3734091) and intron7 DIP (rs28360317) polymorphism sites, there was no difference in the distribution between the lung cancer and control groups. The analyzing results of joint effect for smoking habit and XRCC4 G-1394T polymorphism was that people with GT genotype and smoking habit present the highest risk of lung cancer than other groups (OR=2.31, 95% CI=1.43–3.72). The G allele of the XRCC4 G-1394T may be responsible for lung carcinogenesis and maybe useful in early detection and prevention of lung cancer.

Keywords: XRCC4, polymorphism, lung cancer, carcinogenesis

DOI: 10.3233/CBM-2009-0617

Journal: Cancer Biomarkers, vol. 5, no. 4-5, pp. 159-165, 2009