DNA repair gene excision repair cross complementing-group 1 (ERCC1) in head and neck squamous cell carcinoma: analysis of methylation and polymorphism (G19007A), protein expression and association with epidemiological and clinicopathological factors
DNA repair gene excision repair cross complementing-group 1 (ERCC1) in head and neck squamous cell carcinoma: analysis of methylation and polymorphism (G19007A), protein expression and association with epidemiological and clinicopathological factors
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DOI：
10.1111/j.1365-2559.2011.04062.x
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发表时间：
2012-02-01
期刊：
影响因子：
6.4
通讯作者：
Carvalho, Heloisa de Andrade
中科院分区：
文献类型：
--
作者：
Costa Lima, Lucianne Maia;de Souza, Ludmilla Regina;Carvalho, Heloisa de Andrade
目的：探讨头颈部鳞状细胞癌（HNSCC）患者切除修复交叉互补组1 (ERCC1) （DNA修复蛋白）（G19007A）多态性、甲基化和免疫组化表达与流行病学和临床病理因素及总生存率的关系。方法和结果：研究组包括84例接受手术和辅助放疗而不进行化疗的HNSCC患者。采用双变量和多变量分析。A基因型变异占79.8%，GG占20.2%，GA占28.6%，AA占51.2%。年龄大于45岁的患者等位基因a变异的患病率较高，ERCC1蛋白免疫组化表达较高（83.3%）[比值比(OR) = 4.86, 95%可信区间（CI）： 1.2 ~ 19.7, P = 0.027]，在晚期患者中也较高（OR= 5.04, 95% CI: 1.07 ~ 23.7, P = 0.041）。在51.2%的样本中发现了甲基化状态，并且在没有远处转移的患者（OR = 6.67, 95% CI: 1.40-33.33, P = 0.019）和晚期患者（OR = 5.04, 95% CI: 1.07-23.7, P = 0.041）中甲基化状态更高。在2年和5年，总生存率分别为55%和36%（中位= 30个月）。结论：我们的研究结果可能反映了这些个体一生中频繁的组织损伤导致的高DNA修复率，以及这些人群中更晚期的疾病表现和更差的预后。
Aims: To evaluate the associations of excision repair cross complementing-group 1 (ERCC1) (DNA repair protein) (G19007A) polymorphism, methylation and immunohistochemical expression with epidemiological and clinicopathological factors and with overall survival in head and neck squamous cell carcinoma (HNSCC) patients.Methods and results: The study group comprised 84 patients with HNSCC who underwent surgery and adjuvant radiotherapy without chemotherapy. Bivariate and multivariate analyses were used. The allele A genotype variant was observed in 79.8% of the samples, GG in 20.2%, GA in 28.6% and AA in 51.2%. Individuals aged more than 45 years had a higher prevalence of the allelic A variant and a high (83.3%) immunohistochemical expression of ERCC1 protein [odds ratio (OR) = 4.86, 95% confidence interval (CI): 1.2-19.7, P = 0.027], which was also high in patients with advanced stage (OR= 5.04, 95% CI: 1.07-23.7, P = 0.041). Methylated status was found in 51.2% of the samples, and was higher in patients who did not present distant metastasis (OR = 6.67, 95% CI: 1.40-33.33, P = 0.019) and in patients with advanced stage (OR = 5.04, 95% CI: 1.07-23.7, P = 0.041). At 2 and 5 years, overall survival was 55% and 36%, respectively (median = 30 months).Conclusion: Our findings may reflect a high rate of DNA repair due to frequent tissue injury during the lifetime of these individuals, and also more advanced disease presentation in this population with worse prognosis.