Lack of correlation between X-ray repair cross-complementing group 1 gene polymorphisms and the susceptibility to colorectal cancer in a Malaysian cohort

Abstract

X-ray repair cross-complementing group 1 (XRCC1) is one of the key components in the base excision repair pathway that repairs erroneous DNA lesions and removes nonbulky base adducts for the maintenance of genome integrity. Studies have revealed that differences in individual DNA repair capacity can impact the interindividual variation in cancer susceptibility, tumour aggressiveness and treatment response. The relationship between XRCC1 and sporadic colorectal cancer (CRC) susceptibility, which is hitherto inconclusive, has been explored in many association studies of different populations. In view of the conflicting findings generated, we aimed to investigate the association between XRCC1 and genetic predisposition to CRC among Malaysians. The present case-control association study was conducted on 130 CRC patients and 212 age-matched healthy controls. The genotyping of XRCC1 Arg194Trp, Arg280His and Arg399Gln single nucleotide polymorphisms was performed with allele-specific real-time PCR approach. This was followed by basic statistical analysis on the single nucleotide polymorphisms and haplotype data obtained. No significant difference in the allele and genotype frequencies was observed between CRC patients and healthy controls (P>0.05). There was also no association observed between XRCC1 haplotypes and CRC (P>0.05). In conclusion, a positive association between XRCC1 gene polymorphisms and CRC risk was not established in our Malaysian population.

XRCC1 serves as a potential prognostic indicator for clear cell renal cell carcinoma and inhibits its invasion and metastasis through suppressing MMP-2 and MMP-9

“…Many studies have indicated that XRCC1 expression is up-regulated in tumor progression and might be a risk factor for tumor progression [ 8 , 11 ]. However, a recent publication showed a lack of correlation between XRCC1 gene polymorphisms and colorectal cancer susceptibility in a Malaysian cohort [ 12 ]. In addition, it has been verified that XRCC1 has a low expression level in many kinds of cancers, and XRCC1 has been proposed to serve as an anti-cancer marker for diagnosis.…”

XRCC1 R194W and R399Q Polymorphisms and Colorectal Cancer Risk in a Northeastern Mexican Population

“…Regarding the R194W polymorphism, like us, most studies showed no association with CRC, namely, Han Chinese [ 13 ], Japanese [ 14 ], Norwegian [ 20 ], Polish [ 22 ], Italian [ 25 ], Mexican [ 29 ], and Malaysian [ 34 ]. However, some Asian studies reported a risk of CRC in carriers of the 194T allele, specifically in Han Chinese (OR = 1.30 (1.04–1.64), P =0.023) [ 8 ], Northeast Chinese (OR = 1.29 (1.07–1.55), P =0.007) [ 32 ], Korean (OR = 2.87 (2.01–4.11), P < 0.0001) [ 9 ], and Iranian (OR = 4.95, (2.11–11.6), P < 0.001) [ 35 ] ( Table 3 ).…”

Association of XRCC1 Arg399Gln and RAD51 135 G>C Polymorphisms and Epidemiologic Risk Factors with Colorectal Cancer Among Selected Filipinos

“…It interacts with PARP1, OGG1, and APE1 to facilitate the BER processes. 29 Among its more than 300 poly- 18,41 These amino acid substitutions influence the protein-protein interactions between XRCC1 and other BER proteins resulting in altered efficiency, function, and damaged DNA repair capacity leading to genetic instability and carcinogenesis. 13,27,28,31,40,44 Findings regarding the associations of XRCC1 Arg399Gln with CRC have been inconsistent.…”

“…It has been associated with CRC among the Kashmiri population 38 , South Koreans 27 , Han Chinese from Jiangsu Province, East China 45 , Japanese 39 , and southwest Iranians. 40 However, lack of association has been noted in a Malaysian cohort 41 , Han Chinese from the southwest region of China 33 , and Mexican patients. 15 The difference in results from the Han Chinese population from two different parts of China has been reported due to differences in the study participants' geographical location and genetic makeup.…”

“…34 It is also associated with breast cancer development among Saudi females 28 , Chinese 35 , and Filipino 36 populations but not among the Finnish population. 37 XRCC1 Arg399Gln is associated with CRC development among Kashmiri 38 , S. Koreans 27 , Japanese 39 , southwest Iranians 40 but not among Malaysians 41 , and Mexican cohorts. 15 Both XRCC1 Arg399Gln and RAD51 G135C have been associated with ovarian cancer among Serbian women.…”