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

Halim, Noor Hanis Abu; Chong, Eric Tzyy Jiann; Goh, Lucky Poh Wah; Chuah, Jitt Aun; See, Edwin Un Hean; Chua, Kek Heng; Lee, Ping-Chin

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저자정보: Halim, Noor Hanis Abu (Biotechnology Programme, Faculty of Science and Natural Resources, Universiti Malaysia Sabah) Chong, Eric Tzyy Jiann (Biotechnology Programme, Faculty of Science and Natural Resources, Universiti Malaysia Sabah) Goh, Lucky Poh Wah (Biotechnology Programme, Faculty of Science and Natural Resources, Universiti Malaysia Sabah) Chuah, Jitt Aun (Surgery Department, Queen Elizabeth Hospital) See, Edwin Un Hean (Surgery Department, Queen Elizabeth Hospital) Chua, Kek Heng (Department of Biomedical Science, Faculty of Medicine, University of Malaya) Lee, Ping-Chin (Biotechnology Programme, Faculty of Science and Natural Resources, Universiti Malaysia Sabah)

저널정보: 아시아태평양암예방학회 Asian Pacific journal of cancer prevention : APJCP Asian Pacific journal of cancer prevention : APJCP 제17권 제4호

발행연도: 2016.1

수록면: 1,925 - 1,931 (7page)

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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 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 ${\geq}50years$ 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.

#Gastrointestinal cancer #Sabah population #XRCC1 polymorphisms

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Halim, Noor Hanis Abu

소속기관 Biotechnology Programme, Faculty of Science and Natural Resources, Universiti Malaysia Sabah