Liu Zhensheng, Wang Luo, Wang Li-E, Sturgis Erich M, Wei Qingyi
Department of Epidemiology, The University of Texas M.D. Anderson Cancer Center, Box 189, 1515 Holcombe Boulevard, Houston, TX 77030, USA.
Cancer Lett. 2008 Sep 8;268(1):158-65. doi: 10.1016/j.canlet.2008.03.034. Epub 2008 May 1.
DNA-methyltransferase-3B (DNMT3B) may play an oncogenic role during tumorigenesis, and its genetic variants have been reportedly to be associated with risk of several cancers, but few studies have investigated their roles in squamous cell carcinoma of the head and neck cancer (SCCHN). Here we report a hospital-based case-control study with 832 SCCHN patients and 843 cancer-free controls of non-Hispanic whites that evaluated the association between two DNMT3B single nucleotide polymorphisms (SNPs) DNMT3B -149C>T (rs2424913) and DNMT3B -579G>T (rs2424909) in the promoter region and risk of SCCHN. We found that compared with C-allele carriers, the DNMT3B -149 TT genotype was statistically significantly associated with increased risk of SCCHN (adjusted OR, 1.35, 95% CI, 1.01-1.80, P=0.043), whereas the DNMT3B -579 TT genotype showed only a non-statistically significant risk compared with G-allele carriers. Further analysis of the effects of combined genotypes suggested that subjects with either DNMT3B -149 TT or DNMT3B -579 TT homozygous genotypes had statistically significantly increased risk of SCCHN (adjusted OR=1.36, 95% CI=1.07-1.73, P=0.013). Stratification analysis showed a more profound risk in the subgroups of the young (< or =57 years, the median age of the controls), males, current smokers, current drinkers, and patients with primary tumor sites of pharynx and larynx. This large study provides reliable risk estimates for associations between DNMT3B variants and SCCHN risk in non-Hispanic whites, and our findings are consistent with that of previously reported cancer case-control studies of other cancers. Further mechanistic studies are needed to unravel the underlying molecular mechanisms.
DNA甲基转移酶3B（DNMT3B）在肿瘤发生过程中可能发挥致癌作用，据报道其基因变异与多种癌症的风险相关，但很少有研究调查它们在头颈部鳞状细胞癌（SCCHN）中的作用。在此，我们报告一项基于医院的病例对照研究，该研究纳入了832例SCCHN患者和843名非西班牙裔白人无癌对照，评估启动子区域两个DNMT3B单核苷酸多态性（SNP）即DNMT3B -149C>T（rs2424913）和DNMT3B -579G>T（rs2424909）与SCCHN风险之间的关联。我们发现，与C等位基因携带者相比，DNMT3B -149 TT基因型与SCCHN风险增加在统计学上具有显著相关性（校正比值比，1.35，95%可信区间，1.01 - 1.80，P = 0.043），而与G等位基因携带者相比，DNMT3B -579 TT基因型仅显示出无统计学意义的风险。对组合基因型效应的进一步分析表明，携带DNMT3B -149 TT或DNMT3B -579 TT纯合基因型的受试者患SCCHN的风险在统计学上显著增加（校正比值比 = 1.36，95%可信区间 = 1.07 - 1.73，P = 0.013）。分层分析显示，在年轻（≤57岁，对照组的中位年龄）、男性、当前吸烟者、当前饮酒者以及原发肿瘤部位为咽和喉的患者亚组中风险更为显著。这项大型研究为非西班牙裔白人中DNMT3B变异与SCCHN风险之间的关联提供了可靠的风险估计，我们的发现与先前报道的其他癌症病例对照研究结果一致。需要进一步的机制研究来阐明潜在的分子机制。
