Combined effects of polymorphisms of DNA-repair protein genes and metabolic enzyme genes on the risk of cholangiocarcinoma

• Published in: Japanese journal of clinical oncology Vol. 43; no. 12; pp. 1190 - 1194
• Main 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
• Format: Journal Article
• Language: English
• Published: England 01.12.2013
• Subjects: Alanine; Arginine; Bile Duct Neoplasms - genetics; Bile Ducts, Intrahepatic; Cholangiocarcinoma - genetics; Cysteine; DNA Glycosylases - genetics; DNA Repair - genetics; DNA-Binding Proteins - genetics; Genotype; Glutamine; Glutathione Transferase - genetics; Histidine; Humans; Opisthorchis viverrini; Poly (ADP-Ribose) Polymerase-1; Poly(ADP-ribose) Polymerases - genetics; Polymerase Chain Reaction; Polymorphism, Single Nucleotide; Risk Assessment; Risk Factors; Serine; Valine; X-ray Repair Cross Complementing Protein 1; epidemiology-prevention; carcinogenesis; GI-hepatobiliary-basic; genetics-carcinogenesis
• ISSN: 0368-2811; 1465-3621
• DOI: 10.1093/jjco/hyt138

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. 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. 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. 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.