title: 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.
  
  
  METHODS
  We performed genotyping for both SNPs for 250 GIC patients and 572 healthy volunteers using a polymerase chain reaction- restriction 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.
authors.affiliation: Biotechnology Programme, Faculty of Science and Natural Resources, Universiti Malaysia Sabah, Malaysia E-mail : leepc@ums.edu.my.
authors.forename: Noor Hanis Abu
authors.initials: NH
authors.lastname: Halim
authors.forename: Eric Tzyy Jiann
authors.initials: ET
authors.lastname: Chong
authors.forename: Lucky Poh Wah
authors.initials: LP
authors.lastname: Goh
authors.forename: Jitt Aun
authors.initials: JA
authors.lastname: Chuah
authors.forename: Edwin Un Hean
authors.initials: EU
authors.lastname: See
authors.forename: Kek Heng
authors.initials: KH
authors.lastname: Chua
authors.forename: Ping-Chin
authors.initials: PC
authors.lastname: Lee
mesh_terms: D000328:Adult; D000368:Aged; D000483:Alleles; D014408:Biomarkers, Tumor / Q000235:genetics*; D001893:Borneo / Q000453:epidemiology; D016022:Case-Control Studies; D004268:DNA-Binding Proteins / Q000235:genetics*; D005260:Female; D005500:Follow-Up Studies; D005770:Gastrointestinal Neoplasms / Q000453:epidemiology / Q000209:etiology* / Q000473:pathology; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D010865:Pilot Projects; D016133:Polymerase Chain Reaction; D012150:Polymorphism, Restriction Fragment Length; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D011379:Prognosis; D012307:Risk Factors; D000076105:X-ray Repair Cross Complementing Protein 1
chemical_list: D014408:Biomarkers, Tumor; D004268:DNA-Binding Proteins; D000076105:X-ray Repair Cross Complementing Protein 1; C000619371:XRCC1 protein, human