Songserm Nopparat, Promthet Supannee, Sithithaworn Paiboon, Pientong Chamsai, Ekalaksananan Tipaya, Chopjitt Peechanika, Parkin Donald Maxwell
Department of Epidemiology, Faculty of Public Health, Khon Kaen University, Thailand.
Asian Pac J Cancer Prev. 2011;12(5):1341-5.
Opisthorchis viverrini (OV) infection is the major risk factor for cholangiocarcinoma (CCA). Methylenetetrahydrofolate reductase (MTHFR) is an important enzyme in folate metabolism. Change in MTHFR activity may influence both DNA methylation and synthesis, crucial steps in carcinogenesis. This study aimed to investigate the association between MTHFR polymorphisms and OV infection with CCA risk in a high-incidence area of Thailand. A nested case-control study within cohort study was carried out: 219 subjects with primary CCA were matched with two non-cancer controls from the same cohort on sex, age at recruitment and presence/ absence of OV eggs in stool. At the time of recruitment information on consumption of foodstuffs potentially contaminated by OV was obtained by questionnaire. MTHFR polymorphisms were analyzed using PCR with high resolution melting analysis. Associations between variables and the risk of CCA were assessed using conditional logistic regression. Risk of CCA was related to consumption of a dish of raw freshwater fish (Koi- Pla) with clear dose-response effects, and there were joint effects on CCA risk between MTHFR polymorphisms and consumption of dishes containing raw- and/or semi-raw freshwater fish. This study provides evidence to support a relationship of increased susceptibility to CCA in individuals with MTHFR variants, especially for those individuals who have OV infection or consume semi-raw freshwater fish (acting either as a source of OV or of pre-formed nitrosamine). Folate may play an important role in OV-related cholangiocarcinogenesis by upsetting the balance between DNA methylation and synthesis in the folate pathway.
猫后睾吸虫（OV）感染是胆管癌（CCA）的主要危险因素。亚甲基四氢叶酸还原酶（MTHFR）是叶酸代谢中的一种重要酶。MTHFR活性的改变可能会影响DNA甲基化和合成，而这两者是致癌过程中的关键步骤。本研究旨在调查泰国一个高发病地区MTHFR基因多态性与OV感染和CCA风险之间的关联。在队列研究中进行了一项巢式病例对照研究：219例原发性CCA患者与来自同一队列的两名非癌症对照在性别、招募时的年龄以及粪便中是否存在OV卵方面进行匹配。在招募时，通过问卷调查获取了有关食用可能被OV污染的食品的信息。使用高分辨率熔解分析的PCR方法分析MTHFR基因多态性。使用条件逻辑回归评估变量与CCA风险之间的关联。CCA风险与食用一道生淡水鱼（Koi-Pla）有关，具有明显的剂量反应效应，并且MTHFR基因多态性与食用含有生和/或半生淡水鱼的菜肴之间对CCA风险存在联合效应。本研究提供了证据，支持MTHFR变异个体对CCA易感性增加的关系，特别是对于那些感染OV或食用半生淡水鱼（作为OV或预制亚硝胺的来源）的个体。叶酸可能通过破坏叶酸途径中DNA甲基化和合成之间的平衡，在与OV相关的胆管癌发生中发挥重要作用。
