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

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.

Single Nucleotide Polymorphism (K589E) of the EXO1 Gene: Association with Colorectal Cancer Susceptibility and Clinicopathological Features

“…Jin et al [48] found that K589E polymorphism is associated with the risk of lung cancer in a Chinese population. Similar conclusion was obtained in the study of Taiwanese population, when it was found that the A allele of this polymorphism has a significant association and increase risk of lung cancer (P=0.0097) [35]. Interestingly, in other Taiwanese studies, in 2009, Wang et al [17], Tsai et al [44] & Bau et al [45] reported that the A allele EXO1 K589E conferred a significantly increased risk of gastric, oral and breast …”

“…Regarding the important role of EXO1 in MMR system, this gene has become a famous target gene and widely investigated for its association with several cancers such as oral, CRC, lung and breast [17,35,37,44,47]. In this regard, numerous studies have reported several SNPs of EXO1 as genetic risk factors of cancer.…”

“…MutSα and MutLα have an ATPase activity. ATP binding and hydrolytic activities of hEXO1 are necessary for efficient MMR [18][19][20]. Microsatellite instability (MSI) is caused by a failure of the MMR system.…”

“…According to well-defined role of defective MMR in CRC, it is important to inspect if common variants in the involved genes affect susceptibility to the disease at a population level. Several studies have reported K589E as the genetic risk factor of oral, breast, lung and gastric cancers [17,[35][36][37][38]. Our recent knowledge shows that there isn't any report to evaluate K589E polymorphism and risk of CRC.…”

Individual capacity for detoxification of genotoxic compounds and repair of DNA damage. Commonly used methods for assessment of capacity for DNA repair

“…Mul ple polymorphisms in the EXO1 gene have been described, in the noncoding regions as well as in exons of the gene. One polymorphism, EXO1 Glu589Lys (rs1047840) was found to be associated with suscep bility to lung cancer, breast cancer and gastric cancer in Asian popula ons [159][160][161][162]. The effect of the carriership of the Glu589Lys polymorphism may be modified by smoking status.…”