Hall Janet, Hashibe Mia, Boffetta Paolo, Gaborieau Valerie, Moullan Norman, Chabrier Amelie, Zaridze David, Shangina Oxana, Szeszenia-Dabrowska Neonila, Mates Dana, Janout Vladimir, Fabiánová Eleonóra, Holcatova Ivana, Hung Rayjean J, McKay James, Canzian Federico, Brennan Paul
International Agency for Research on Cancer, Lyon, France.
Carcinogenesis. 2007 Mar;28(3):665-71. doi: 10.1093/carcin/bgl160. Epub 2006 Oct 13.
Cancers of the upper aerodigestive tract (UADT), comprising the oral cavity, pharynx, larynx and oesophagus, account for 5.2% of all cancers cases worldwide. The major risk factors, tobacco and alcohol can directly or indirectly generate DNA damage, which if unrepaired can give rise to mutations, unregulated cell growth and apoptosis induction. To clarify the role of DNA repair and cell cycle control proteins in UADT cancer susceptibility, we studied the risk in relation to 28 SNPs in 18 DNA repair enzymes and 9 SNPs in 7 cell cycle control genes. A case-control study was conducted from 2000 to 2002 in six centers from Romania, Poland, Russia, Slovakia and the Czech Republic. Patients diagnosed with squamous cell carcinoma of the UADT (n=811) and controls with a recent diagnosis of diseases unrelated to tobacco and alcohol (n=1083) were recruited. For UADT cancer risk, associations were observed for the homozygous carriers of the variant alleles of MGMT L84F [odds ratio (OR) 2.35, 95% confidence interval (CI) 1.32-4.20], MGMT 171C > T (OR 2.24, 95% CI 1.20-4.17) and OGG1 S326C (OR 2.07, 95% CI 1.15-3.73) whilst three variants were associated with a protective effect (XPA 23G > A, P for trend 0.022, APEX Q51H, P for trend 0.036, CHEK2 intron 9-200T > C, P for trend 0.009). Several other sequence variants showed associations with specific cancers without an overall association with UADT cancer. While some of these associations are consistent with previous studies, we cannot rule out the possibility of false-positive associations. The positive findings should be explored in another large-scale study on UADT cancers.
上呼吸消化道（UADT）癌症包括口腔癌、咽癌、喉癌和食道癌，占全球所有癌症病例的5.2%。主要风险因素烟草和酒精可直接或间接造成DNA损伤，若未得到修复，可能导致突变、细胞生长失控和诱导细胞凋亡。为阐明DNA修复和细胞周期调控蛋白在上呼吸消化道癌症易感性中的作用，我们研究了与18种DNA修复酶中的28个单核苷酸多态性（SNP）以及7个细胞周期调控基因中的9个SNP相关的风险。2000年至2002年在罗马尼亚、波兰、俄罗斯、斯洛伐克和捷克共和国的六个中心开展了一项病例对照研究。招募了被诊断为上呼吸消化道鳞状细胞癌的患者（n = 811）以及近期被诊断患有与烟草和酒精无关疾病的对照者（n = 1083）。对于上呼吸消化道癌症风险，观察到O - 6 - 甲基鸟嘌呤 - DNA甲基转移酶（MGMT）L84F变异等位基因的纯合携带者存在关联[比值比（OR）2.35，95%置信区间（CI）1.32 - 4.20]、MGMT 171C>T（OR 2.24，95%CI 1.20 - 4.17）和8 - 氧鸟嘌呤DNA糖基化酶1（OGG1）S326C（OR 2.07，95%CI 1.15 - 3.73），而有三个变异与保护作用相关（XPA 23G>A，趋势P值0.022；脱嘌呤嘧啶核酸内切酶1（APEX）Q51H，趋势P值0.036；细胞周期检测点激酶2（CHEK2）内含子9 - 200T>C，趋势P值0.009）。其他几个序列变异显示与特定癌症存在关联，但与上呼吸消化道癌症无总体关联。虽然其中一些关联与先前的研究一致，但我们不能排除假阳性关联的可能性。这些阳性发现应在另一项关于上呼吸消化道癌症的大规模研究中进行探索。
