The human OGG1 DNA repair enzyme and its association with orolaryngeal cancer risk
The human OGG1 DNA repair enzyme and its association with orolaryngeal cancer risk
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DOI：
10.1093/carcin/23.7.1229
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发表时间：
2002-07-01
期刊：
影响因子：
4.7
通讯作者：
Lazarus, P
中科院分区：
文献类型：
--
作者：
Elahi, A;Zheng, Z;Lazarus, P
人OGG 1（hOGG 1）基因编码DNA糖基化酶，其参与从氧化损伤的DNA切除修复8-羟基-2 '-脱氧鸟嘌呤（8-OH-dG）。为了确定hOGG 1是否在口咽癌的风险中起作用，我们筛选了正常口咽组织标本的hOGG 1表达，并评估了hOGG 1 Ser 326 Cys多态性在口咽癌风险中的作用。通过逆转录-聚合酶链反应测定呼吸消化道组织总RNA的hOGG 1表达，并通过聚合酶链反应-限制性片段长度多态性分析从169例高加索人口咽癌病例和338例种族、性别和年龄匹配的对照中分离的颊细胞DNA进行hOGG 1基因分型。hOGG 1 mRNA在扁桃体、舌、口底、喉、食管等呼吸消化道组织中均有表达。hOGG 1 326（Ser）/326（Cys）（比值比[OR] = 1.6，95%可信区间[CI] = 1.04-2.6）和hOGG 1 326（Cys）/326（Cys）（OR = 4.1，95% CI = 1.3-13）基因型均显著增加了口咽癌的风险。虽然hOGG 1基因型在从不吸烟者中没有观察到口咽癌风险的显著差异，但在吸烟者中具有纯合多态性hOGG 1 326（Cys）/326（Cys）基因型的受试者中观察到口咽癌风险增加（>100支香烟终生; OR = 4.8，95%CI = 1.3-18）。类似地，虽然在从不饮酒者中没有观察到相关性，但在饮酒者中观察到hOGG 1 326（Cys）/326（Cys）基因型的风险显著增加（>1次/周; OR = 6.9，95%CI = 1.6-29）。这些结果表明，hOGG 1可能在修复8-OH-dG加合物在呼吸消化道和hOGG 1 Ser 326 Cys多态性在吸烟和酒精相关的口咽癌的风险中起着重要的作用。
The human OGG1 (hOGG1) gene encodes a DNA glycosylase that is involved in the excision repair of 8-hydroxy-2'-deoxyguanine (8-OH-dG) from oxidatively-damaged DNA. To determine whether hOGG1 plays a role in risk for orolaryngeal cancer, we screened normal orolaryngeal tissue specimens for hOGG1 expression and assessed the role of the hOGG1 Ser326Cys polymorphism in risk for orolaryngeal cancer. hOGG1 expression was determined by reverse transcription-polymerase chain reaction of total RNA from aerodigestive tract tissues, and hOGG1 genotyping was performed by polymerase chain reaction-restriction fragment length polymorphism analysis of buccal cell DNA isolated from 169 Caucasian orolaryngeal cancer cases and 338 race-, sex- and age-matched controls. hOGG1 mRNA was detected in all aerodigestive tract tissues tested including tonsil, tongue, floor of mouth, larynx and esophagus. Significantly increased risk for orolaryngeal cancer was observed for both the hOGG1 326(Ser)/326(Cys) (odds ratio [OR] = 1.6, 95% confidence interval [CI] = 1.04-2.6) and hOGG1 326(Cys)/326(Cys) (OR = 4.1, 95% CI = 1.3-13) genotypes. Although no significant difference in risk for orolaryngeal cancer was observed for hOGG1 genotypes in never-smokers, increased risk for orolaryngeal cancer was observed for subjects with the homozygous polymorphic hOGG1 326(Cys)/326(Cys) genotype in smokers (>100 cigarettes lifetime; OR = 4.8, 95% CI = 1.3-18). Similarly, although no association was observed in never drinkers of alcohol, significantly increased risk was observed for the hOGG1 326(Cys)/326(Cys) genotype in alcohol drinkers (>1 shot/week; OR = 6.9, 95% CI = 1.6-29). These results suggest that hOGG1 may play an important role in the repair of 8-OH-dG adducts in the aerodigestive tract and that the hOGG1 Ser326Cys polymorphism plays an important role in risk for smoking- and alcohol-related orolaryngeal cancer.