Variant Alleles in XRCC1 Arg194Trp and Arg399Gln Polymorphisms Increase Risk of Gastrointestinal Cancer in Sabah, North Borneo

Abstract

Background: The XRCC1 protein facilitates various DNA repair pathways; single-nucleotide polymorphisms (SNPs) in this gene are associated with a risk of gastrointestinal cancer (GIC) with inconsistent results, but no data have been previously reported for the Sabah, North Borneo, population. We accordingly investigated the XRCC1 Arg194Trp and Arg399Gln SNPs in terms of GIC risk in Sabah. Materials and Methods: We performed genotyping for both SNPs for 250 GIC patients and 572 healthy volunteers using a polymerase chain reactionrestriction fragment length polymorphism approach. We validated heterozygosity and homozygosity for both SNPs using direct sequencing. Results: The presence of a variant 194Trp allele in the Arg194Trp SNP was significantly associated with a higher risk of GIC, especially with gastric and colorectal cancers. We additionally found that the variant 399Gln allele in Arg399Gln SNP was associated with a greater risk of developing gastric cancer. Our combined analysis revealed that inheritance of variant alleles in both SNPs increased the GIC risk in Sabah population. Based on our etiological analysis, we found that subjects ≥50 years and males who carrying the variant 194Trp allele, and Bajau subjects carrying the 399Gln allele had a significantly increased risk of GIC. Conclusions: Our findings suggest that inheritance of variant alleles in XRCC1 Arg194Trp and Arg399Gln SNPs may act as biomarkers for the early detection of GIC, especially for gastric and colorectal cancers in the Sabah population.

XRCC1 Gene Polymorphisms and miR-21 Expression in Patients with Colorectal Carcinoma

“…In agreement with our results, Halim et al [14] reported that the 194Trp allele is significantly associated with high risk for the development of CRC. The frequency of the 194Trp allele in our study was similar to that previously reported in studies from Egypt and Mexico [15,16].…”

Influence of Two DNA Repair Pathway Polymorphisms in Colorectal Cancer Risk in Southwest Iran

“…The outcomes of some investigation about the association of XRCC1 (rs25487) polymorphism with colorectal cancer risk have been contradictory. For example, two recent studies indicated association with increased risk of colorectal cancer (Karam et al, 2016;Abu Halim et al, 2016), while a case-control study in Sweden found no association with CRC risk (Salimzadeh et al, 2020). Also, other findings about the association of OGG1 (rs1052133) polymorphism with susceptibility to CRC remain controversial (Lai et al, 2016;Zou et al, 2016).…”

A Review of Gastric Cancer Research in Malaysia

“…The 399Gln allele frequency was found higher when compared to Egyptian, Han Chinese, Japanese, Korean and Western Mexican populations but was lower than in the Thai population gastrointestinal cancer population. (Halim et al, 2016) Rajadurai (2017) has found human epidermal growth factor receptor2 (HER2) overexpression, a biomarker of breast cancer, in advanced GCa and gastroesophageal junction cancer. HER2 overexpression was evident in nearly 24.6% (56/288) of the Malaysian,and significantly more among males and diffuse-type tumors.…”