Akbari Mohammad R, Malekzadeh Reza, Shakeri Ramin, Nasrollahzadeh Dariush, Foumani Maryam, Sun Yulong, Pourshams Akram, Sadjadi Alireza, Jafari Elham, Sotoudeh Masoud, Kamangar Farin, Boffetta Paolo, Dawsey Sanford M, Ghadirian Parviz, Narod Steven A
Digestive Disease Research Center, Tehran University of Medical Sciences, Tehran, Iran.
Cancer Res. 2009 Oct 15;69(20):7994-8000. doi: 10.1158/0008-5472.CAN-09-1149. Epub 2009 Oct 13.
There is a region with a high risk for esophageal squamous cell carcinoma (ESCC) in the northeast of Iran. Previous studies suggest that hereditary factors play a role in the high incidence of cancer in the region. We selected 22 functional variants (and 130 related tagSNPs) from 15 genes that have been associated previously with the risk of ESCC. We genotyped a primary set of samples from 451 Turkmens (197 cases and 254 controls). Seven of 152 variants were associated with ESCC at the P = 0.05 level; these single nucleotide polymorphisms were then studied in a validation set of 549 cases and 1,119 controls, which included both Turkmens and non-Turkmens. The association observed for a functional variant in ADH1B was confirmed in the validation set, and that of a tagSNP in MGMT, the association was borderline significant in the validation set, after correcting for multiple testing. The other 5 variants that were associated in the primary set were not significantly associated in the validation set. The histidine allele at codon 48 of ADH1B gene was associated with a significantly decreased risk of ESCC in the joint data set (primary and validation set) under a recessive model (odds ratio, 0.41; 95% confidence interval, 0.29-0.76; P = 4 x 10(-4)). The A allele of the rs7087131 variant of MGMT gene was associated with a decreased risk of ESCC under a dominant model (odds ratio, 0.79; 95% confidence interval, 0.64-0.96; P = 0.02). These results support the hypothesis that genetic predisposition plays a role in the high incidence of ESSC in Iran.
伊朗东北部存在一个食管鳞状细胞癌（ESCC）高风险区域。先前的研究表明，遗传因素在该地区癌症的高发病率中起作用。我们从先前与ESCC风险相关的15个基因中选择了22个功能变异（以及130个相关标签单核苷酸多态性）。我们对来自451名土库曼人（197例病例和254名对照）的一组主要样本进行了基因分型。152个变异中的7个在P = 0.05水平与ESCC相关；然后在包括土库曼人和非土库曼人的549例病例和1119名对照的验证集中研究这些单核苷酸多态性。在验证集中证实了ADH1B中一个功能变异的关联，而MGMT中一个标签单核苷酸多态性的关联在经过多重检验校正后在验证集中接近显著。在主要数据集中相关的其他5个变异在验证集中未显著相关。在隐性模型下，ADH1B基因第48位密码子的组氨酸等位基因在联合数据集（主要数据集和验证集）中与ESCC风险显著降低相关（优势比，0.41；95%置信区间, 0.29 - 0.76；P = 4×10⁻⁴）。MGMT基因rs7087131变异的A等位基因在显性模型下与ESCC风险降低相关（优势比，0.79；95%置信区间, 0.64 - 0.96；P = 0.02）。这些结果支持了遗传易感性在伊朗ESCC高发病率中起作用这一假说。
