The Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education and Chinese Ministry of Health, Qilu Hospital of Shandong University, Jinan, 250012, China.
BMC Gastroenterol. 2011 Jun 14;11:74. doi: 10.1186/1471-230X-11-74.
The purpose of this study was to evaluate the association of multi-genotype polymorphisms with the stepwise progression of esophageal squamous cell cancer (ESCC) and the possibility of predicting those at higher risk.
A total of 1,004 subjects were recruited from Feicheng County, China, between Jan. 2004 and Dec. 2007 and examined by endoscopy for esophageal lesions. These subjects included 270 patients with basal cell hyperplasia (BCH), 262 patients with esophageal squamous cell dysplasia (ESCD), 226 patients with ESCC, and 246 controls with Lugol-voiding area but diagnosed as having normal esophageal squamous epithelial cells by histopathology. The genotypes for CYP2E1 G1259C, hOGG1 C326G, MTHFR C677T, MPO G463A, and ALDH2 allele genes were identified in blood samples collected from all participants.
The alleles ALDH2 and MTHFR C677T were critical for determining individual susceptibility to esophageal cancer. Compared to the ALDH 11 genotype, the ALDH 22 genotype was significantly associated with increased risks of BCH, ESCD, and ESCC. However, the TT genotype of MTHFR C677T only increased the risk of ESCC. Further analysis revealed that the combination of the high-risk genotypes 22/12 of ALDH 2 and TT/TC of MTHFR C677T increased the risk of BCH by 4.0 fold, of ESCD by 3.7 fold, and ESSC by 8.72 fold. The generalized odds ratio (ORG) of the two combined genotypes was 1.83 (95%CI: 1.55-2.16), indicating a strong genetic association with the risk of carcinogenic progression in the esophagus.
The study demonstrated that the genotypes ALDH2*2 and MTHFR 677TT conferred elevated risk for developing esophageal carcinoma and that the two susceptibility genotypes combined to synergistically increase the risk.
本研究旨在评估多基因型多态性与食管鳞状细胞癌（ESCC）的逐步进展的关联，并探讨其预测高危人群的可能性。
2004 年 1 月至 2007 年 12 月期间，我们在中国肥城地区招募了 1004 名受试者，对他们进行内镜检查以发现食管病变。这些受试者包括 270 例基底细胞增生（BCH）患者、262 例食管鳞状细胞异型增生（ESCD）患者、226 例 ESCC 患者和 246 例卢戈氏碘染色阳性但经组织病理学诊断为食管正常鳞状上皮细胞的对照者。所有参与者均采集血样，检测 CYP2E1 G1259C、hOGG1 C326G、MTHFR C677T、MPO G463A 和 ALDH2 等位基因的基因型。
ALDH2 和 MTHFR C677T 等位基因对个体患食管癌的易感性有重要影响。与 ALDH11 基因型相比，ALDH22 基因型与 BCH、ESCD 和 ESCC 的发病风险显著相关。然而，MTHFR C677T 的 TT 基因型仅增加了 ESCC 的发病风险。进一步分析显示，ALDH2 高风险基因型 22/12 和 MTHFR C677T 的 TT/TC 基因型的组合使 BCH 的发病风险增加了 4.0 倍，ESCD 的发病风险增加了 3.7 倍，ESCC 的发病风险增加了 8.72 倍。两种联合基因型的广义比值比（ORG）为 1.83（95%CI：1.55-2.16），表明它们与食管癌变进展的遗传相关性较强。
本研究表明，ALDH2*2 和 MTHFR 677TT 基因型增加了患食管癌的风险，且两种易感基因型的组合可协同增加风险。
