*Department of Paediatrics, National Hospital Organization Fukuoka National Hospital, 1-39-4 Yakatabaru, Minami-ku, Fukuoka 811-1394, Japan.
Jpn J Clin Oncol. 2013 Dec;43(12):1190-4. doi: 10.1093/jjco/hyt138. Epub 2013 Sep 18.
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.
肝吸虫是胆管癌的一个风险因素，但并非所有感染者都会发展为胆管癌。我们研究了具有不同炎症相关脱氧核糖核酸损伤修复能力的碱基切除修复酶基因突变是否起关键作用，以及这些基因的可能影响是否会因代谢酶（包括谷胱甘肽 S-转移酶 mu1 和谷胱甘肽 S-转移酶 theta1）的基因突变而增加或减少。
我们对三个基因的五个非同义单核苷酸多态性进行了基因分型，包括人类 8-氧鸟嘌呤糖苷酶 1 丝氨酸 326 半胱氨酸、X 射线修复交叉互补蛋白 1 精氨酸 194 色氨酸、精氨酸 280 组氨酸和精氨酸 399 谷氨酰胺以及多聚（腺嘌呤二磷酸核糖）聚合酶 1 缬氨酸 762 丙氨酸的 87-94 例匹配病例对照对，并研究了这些多态性与胆管癌风险之间的关系。
任何单一的多态性与胆管癌的风险都没有明显的关联。然而，当同时考虑谷胱甘肽 S-转移酶 mu1 多态性时，人类 8-氧鸟嘌呤糖苷酶 1 密码子 326 多态性与风险降低有关；比值比分别为 1.00（参考）、0.06（95%置信区间 0.01-0.53）、0.06（0.01-0.54）和 0.14（0.02-1.08），分别为人类 8-氧鸟嘌呤糖苷酶 1 丝氨酸/丝氨酸和谷胱甘肽 S-转移酶 mu1 野生型、丝氨酸/丝氨酸和谷胱甘肽 S-转移酶 mu1 缺失型、丝氨酸/半胱氨酸或半胱氨酸/半胱氨酸和谷胱甘肽 S-转移酶 mu1 野生型、丝氨酸/半胱氨酸或半胱氨酸/半胱氨酸和谷胱甘肽 S-转移酶 mu1 缺失型（P<0.01）。进一步调整抗肝吸虫抗体、吸烟和饮酒的存在情况并未改变这种低风险。脱氧核糖核酸修复基因多态性和谷胱甘肽 S-转移酶的其他组合与胆管癌的风险无关。
本研究结果表明，如果受损细胞在恶性转化前大量死亡，脱氧核糖核酸修复基因人类 8-氧鸟嘌呤糖苷酶 1 能力降低可能与风险降低有关。
