Songserm Nopparat, Promthet Supannee, Pientong Chamsai, Ekalaksananan Tipaya, Chopjitt Peechanika, Wiangnon Surapon
Department of Community Health, Faculty of Public Health, Ubon Ratchathani Rajabhat University, Ubon Ratchathani, Thailand.
Department of Epidemiology, Faculty of Public Health, Khon Kaen University, Khon Kaen, Thailand.
BMJ Open. 2014 Oct 21;4(10):e005447. doi: 10.1136/bmjopen-2014-005447.
Cholangiocarcinoma (CCA) is the most common malignancy in a Northeast Thai population. Smoking and alcohol drinking are associated with the production of free radical intermediates, which can cause several types of DNA lesions. Reduced repair of these DNA lesions would constitute an important risk factor for cancer development. We therefore examined whether polymorphisms in DNA base-excision repair (BER) genes, XRCC1 G399A and OGG1 C326G, were associated with CCA risk and whether they modified the effect of smoking and alcohol drinking in the Thai population.
A nested case-control study within the cohort study was conducted: 219 participants with primary CCA were each matched with two non-cancer controls from the same cohort on sex, age at recruitment and the presence/absence of Opisthorchis viverrini eggs in stools. Smoking and alcohol consumption were assessed on recruitment. Polymorphisms in BER genes were analysed using a PCR with high-resolution melting analysis. The associations were assessed using conditional logistic regression.
Our results suggest that, in the Thai population, polymorphisms in XRCC1 and OGG1 genes, particularly in combination, are associated with increased susceptibility to CCA, and that their role as modifiers of the effect of smoking and alcohol consumption influences the risk of CCA.
Better ways of reducing habitual smoking and alcohol consumption, targeted towards subgroups which are genetically susceptible, are recommended. CCA is a multifactorial disease, and a comprehensive approach is needed for its effective prevention. This approach would also have the additional advantage of reducing the onset of other cancers.
胆管癌（CCA）是泰国东北部人群中最常见的恶性肿瘤。吸烟和饮酒与自由基中间体的产生有关，自由基中间体可导致多种类型的DNA损伤。这些DNA损伤修复能力的降低将构成癌症发生的重要危险因素。因此，我们研究了DNA碱基切除修复（BER）基因XRCC1 G399A和OGG1 C326G的多态性是否与CCA风险相关，以及它们是否改变了泰国人群中吸烟和饮酒的影响。
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参与者分别与来自同一队列的两名非癌症对照按性别、招募时年龄以及粪便中是否存在华支睾吸虫卵进行匹配。在招募时评估吸烟和饮酒情况。使用高分辨率熔解分析的聚合酶链反应（PCR）分析BER基因的多态性。使用条件逻辑回归评估相关性。
我们的结果表明，在泰国人群中，XRCC1和OGG1基因的多态性，尤其是联合存在时，与CCA易感性增加相关，并且它们作为吸烟和饮酒影响的修饰因子会影响CCA风险。
建议针对遗传易感亚组采取更好的方法来减少习惯性吸烟和饮酒。CCA是一种多因素疾病，需要采取综合方法进行有效预防。这种方法还具有减少其他癌症发病的额外优势。
