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- Title
Combined Effects of Polymorphisms of DNA-repair Protein Genes and Metabolic Enzyme Genes on the Risk of Cholangiocarcinoma.
- Authors
Zeng, Lu; You, Gyokukou; Tanaka, Hideaki; Srivatanakul, Petcharin; Ohta, Emi; Viwatthanasittiphong, Chutiwan; Matharit, Mantana; Chenvidhya, Dhiraphol; Jedpiyawongse, Adisorn; Tanaka, Masakazu; Fujii, Takahiro; Sripa, Banchob; Ohshima, Kazuhiko; Miwa, Masanao; Honjo, Satoshi
- Abstract
Objective Although Opisthorchis viverrini is a risk factor for cholangiocarcinoma, not all the infected individuals develop cholangiocarcinoma. We investigated whether the base excision repair enzyme gene polymorphisms with differentiated repair capacities of inflammation-related deoxyribonucleic acid damage may play a key role and such possible effects from those genes may be increased or diminished in co-existence of polymorphisms of metabolic enzymes, including glutathione-S-transferases mu 1 and glutathione-S-transferases θ1. Methods We genotyped five non-synonymous single-nucleotide polymorphisms of three genes, including the human homolog of the 8-oxoguanine glycosylase 1 Ser326Cys, X-ray repair cross-complementing protein 1 Arg194Trp, Arg280His and Arg399Gln and poly (adenosine diphosphate ribose) polymerase 1 Val762Ala in 87–94 matched case–control pairs, and examined relations between those polymorphisms and the risk of cholangiocarcinoma. Results Any single polymorphism did not have a measurable association with the risk of cholangiocarcinoma. However, when considering glutathione-S-transferases mu 1 polymorphism together, the human homolog of the 8-oxoguanine glycosylase 1 codon 326 polymorphism was related to the decreased risk; odds ratios were 1.00 (reference), 0.06 (95% confidence interval 0.01–0.53), 0.06 (0.01–0.54) and 0.14 (0.02–1.08) for persons with human homolog of the 8-oxoguanine glycosylase 1 Ser/Ser and glutathione-S-transferases mu 1 wild, ones with Ser/Ser and glutathione-S-transferases mu 1 null, ones with Ser/Cys or Cys/Cys and glutathione-S-transferases mu 1 wild and ones with Ser/Cys or Cys/Cys and glutathione-S-transferases mu 1 null, respectively (P for interaction <0.01). Further adjustment for the presence of anti-Opisthorchis viverrini antibody, smoking and alcohol drinking did not change the decreased risk. Other combinations of deoxyribonucleic acid-repair gene polymorphism and glutathione-S-transferases were not associated with the risk of cholangiocarcinoma. Conclusions The present findings suggested that decreased capacity of deoxyribonucleic acid-repair gene, human homolog of the 8-oxoguanine glycosylase 1, may be related to decreased risk if much damaged cells die before malignant transformation.
- Publication
Japanese Journal of Clinical Oncology, 2013, Vol 43, Issue 12, p1190
- ISSN
0368-2811
- Publication type
Article
- DOI
10.1093/jjco/hyt138