Sequence Variation in X-ray Cross Complimenting (XRCC4, XRCC5, XRCC6 and XRCC7) Genes and the Risk of Gastrointestinal Cancer in South-Western Maharashtra: A Hospital Based Case-Control Study.

OBJECTIVE

A number of X-ray repair cross complementing group (XRCC) genes are found to be involved in the DNA repair by the repair of single strand breaks (SSBs). Variation in these genes may lead to variation in DNA repair capacity, thereby increasing the genetic susceptibility to numerous human cancers. Among the known genetic polymorphisms of the DNA repair genes, there are many functional genetic variants have been identified in the XRCC genes particularly XRCC4, XRCC5, XRCC6 and XRCC7 that shows the positive association with the multiple cancers including cancers of GI tract. Therefore, in the present study, polymorphic variants of XRCC4, XRCC5, XRCC6 and XRCC7 were chosen to be studied in association with gastrointestinal cancer susceptibility in the south western Maharashtrian population.  Methods: A total of 200 histologically confirmed cases of gastrointestinal cancer (GI) and 200 hospital-based controls were included in the study. The genotyping for XRCC4, XRCC5, XRCC6 and XRCC7 genes was carried out by polymerase chain reaction-restriction fragment length polymorphism.

RESULTS

We found that tobacco consumption in any form either smoking or chewing (OR = 4.03; 95% CI: 2.65-6.11) and alcohol drinking habit (OR = 4.45; CI: 2.15-9.22) is strongly associated with gastrointestinal cancer risk.  Similarly, data analysis of cases and control group showed that XRCC4.2 G1394T is significantly associated with GI cancer risk. Our studies also revealed that fewer repeats (1R/1R, 0R/0R) of XRCC5 in the promoter region were found to be associated with the increased risk of GI cancer. In case of XRCC7 6721G>T our findings suggest a strong association with development of GI cancer risk in south-western Maharashtrian population.  However, we did not find any association of polymorphic variants of XRCC4.1 cd247, XRCC4.5 Intron-7 and XRCC6 61C>G with GI cancer risk in the study population. However, multicentric studies with larger sample size are needed to substantiate the findings.