Hong-Xue Ji1, Wen-Shin Chang1, Chia-Wen Tsai2, Ju-Yu Wang3, Nai-Kuei Huang4, An-Sheng Lee5, Ming-Yi Shen6, Wei-Yu Chen7, Yao-Chang Chiang8, Tzu-Ching Shih9, Chin-Mu Hsu10, Da-Tian Bau11. 1. Graduate Institute of Clinical Medical Science, China Medical University, Taichung, Taiwan, R.O.C. Terry Fox Cancer Research Laboratory, China Medical University Hospital, Taichung, Taiwan, R.O.C. 2. Terry Fox Cancer Research Laboratory, China Medical University Hospital, Taichung, Taiwan, R.O.C. 3. Basic Medical Science, Department of Nursing, Hung-Kuang University, Taichung, Taiwan, R.O.C. 4. National Research Institute of Chinese Medicine, Taipei, Taiwan, R.O.C. 5. Department of Medicine, Mackay Medical College, New Taipei, Taiwan, R.O.C. L5 Research Center, China Medical University Hospital, Taichung, Taiwan, R.O.C. 6. Graduate Institute of Clinical Medical Science, China Medical University, Taichung, Taiwan, R.O.C. L5 Research Center, China Medical University Hospital, Taichung, Taiwan, R.O.C. 7. L5 Research Center, China Medical University Hospital, Taichung, Taiwan, R.O.C. Graduate Institute of Basic Medical Science, China Medical University, Taichung, Taiwan, R.O.C. 8. Center for Drug Abuse and Addiction, China Medical University Hospital, Taichung, Taiwan, R.O.C. 9. Department of Biomedical Imaging and Radiological Science, China Medical University, Taichung, Taiwan, R.O.C. artbau2@gmail.com e12013@gmail.com shih@mail.cmu.edu.tw. 10. Terry Fox Cancer Research Laboratory, China Medical University Hospital, Taichung, Taiwan, R.O.C. artbau2@gmail.com e12013@gmail.com shih@mail.cmu.edu.tw. 11. Graduate Institute of Clinical Medical Science, China Medical University, Taichung, Taiwan, R.O.C. Terry Fox Cancer Research Laboratory, China Medical University Hospital, Taichung, Taiwan, R.O.C. Department of Bioinformatics and Medical Engineering, Asia University, Taichung, Taiwan, R.O.C. artbau2@gmail.com e12013@gmail.com shih@mail.cmu.edu.tw.
Abstract
AIM: It has been proposed that genetic variations of DNA repair genes confer susceptibility to cancer, and the DNA repair gene xeroderma pigmentosum group D (XPD), the caretaker of genome stability, is thought to play a major role in the nucleotide excision repair system. We investigated three genotypes of XPD, at promoter -114 (rs3810366), and codon 312 (rs1799793), 751 (rs13181), and their associated with gastric cancer susceptibility in a Taiwanese population. MATERIALS AND METHODS: In the present study, 121 patients with gastric cancer and 363 gender- and age-matched healthy controls were recruited and genotyped for XPD by polymerase chain reaction-based restriction fragment length polymorphism (PCR-RFLP) methodology, and the association of XPD genotype with gastric cancer risk was investigated. RESULTS: We found a significant difference in the distribution of A allele-bearing XPD codon 312 genotypes [odds ratio (OR)=1.64, 95% confidence interval (CI)=1.20-2.25, p=0.0019], but not in XPD codon 751 or promoter -114 sites, between the gastric cancer and control groups. Those who had G/A or A/A at XPD codon 312 had a 1.83-fold (95% CI=1.14-2.95, p=0.0159) and 1.87-fold (95% CI=1.04-3.34, p=0.0378) increased risk of gastric cancer compared to those with G/G. The risk for G/A and A/A genotypes had synergistic effects with alcohol drinking (OR=11.27, 95% CI=3.72-34.17, p=0.0001), cigarette smoking (OR=23.20, 95% CI=6.24-86.23, p=0.0001) and Helicobacter pylori infection (OR=5.38, 95% CI=2.76-10.52, p=0.0001) on gastric cancer susceptibility. CONCLUSION: Our findings suggest that the A allele of XPD codon 312 may contribute to gastric carcinogenesis and may be useful for early detection and prevention of gastric cancer. Copyright
AIM: It has been proposed that genetic variations of DNA repair genes confer susceptibility to cancer, and the DNA repair gene xeroderma pigmentosum group D (XPD), the caretaker of genome stability, is thought to play a major role in the nucleotide excision repair system. We investigated three genotypes of XPD, at promoter -114 (rs3810366), and codon 312 (rs1799793), 751 (rs13181), and their associated with gastric cancer susceptibility in a Taiwanese population. MATERIALS AND METHODS: In the present study, 121 patients with gastric cancer and 363 gender- and age-matched healthy controls were recruited and genotyped for XPD by polymerase chain reaction-based restriction fragment length polymorphism (PCR-RFLP) methodology, and the association of XPD genotype with gastric cancer risk was investigated. RESULTS: We found a significant difference in the distribution of A allele-bearing XPD codon 312 genotypes [odds ratio (OR)=1.64, 95% confidence interval (CI)=1.20-2.25, p=0.0019], but not in XPD codon 751 or promoter -114 sites, between the gastric cancer and control groups. Those who had G/A or A/A at XPD codon 312 had a 1.83-fold (95% CI=1.14-2.95, p=0.0159) and 1.87-fold (95% CI=1.04-3.34, p=0.0378) increased risk of gastric cancer compared to those with G/G. The risk for G/A and A/A genotypes had synergistic effects with alcohol drinking (OR=11.27, 95% CI=3.72-34.17, p=0.0001), cigarette smoking (OR=23.20, 95% CI=6.24-86.23, p=0.0001) and Helicobacter pylori infection (OR=5.38, 95% CI=2.76-10.52, p=0.0001) on gastric cancer susceptibility. CONCLUSION: Our findings suggest that the A allele of XPD codon 312 may contribute to gastric carcinogenesis and may be useful for early detection and prevention of gastric cancer. Copyright
Authors: Fei Chen; Sungshim L Park; Lynne R Wilkens; Peggy Wan; Steven N Hart; Chunling Hu; Siddhartha Yadav; Fergus J Couch; David V Conti; Adam J de Smith; Christopher A Haiman Journal: Cancer Res Date: 2022-09-16 Impact factor: 13.312