烟草致癌物解毒酶UGT1A7及其与口咽癌风险的关联。

Tobacco carcinogen-detoxifying enzyme UGT1A7 and its association with orolaryngeal cancer risk.

作者信息

Zheng Z, Park J Y, Guillemette C, Schantz S P, Lazarus P

机构信息

Division of Cancer Control, H. Lee Moffitt Cancer Center and Research Institute, Interdisciplinary Oncology Program and Department of Biochemistry, University of South Florida, Tampa 33612, USA.

出版信息

J Natl Cancer Inst. 2001 Sep 19;93(18):1411-8. doi: 10.1093/jnci/93.18.1411.

DOI:10.1093/jnci/93.18.1411

PMID:11562393

Abstract

BACKGROUND

UDP-glucuronosyltransferase 1A7 (UGT1A7) detoxifies several tobacco carcinogens. We determined whether UGT1A7 expression is observed in normal orolaryngeal tissue and whether UGT1A7 allelic variations are associated with the risk for orolaryngeal cancer.

METHODS

UGT1A7 expression in normal orolaryngeal tissue was determined by semiquantitative reverse transcription-polymerase chain reaction (PCR). Buccal cell DNA isolated from 194 case subjects with orolaryngeal cancer and from 388 control subjects who were matched by sex, age, and race was subjected to UGT1A7 genotyping with the use of combined PCR-restriction fragment length polymorphism and allelic discrimination analysis. All statistical tests were two-sided.

RESULTS

UGT1A7 messenger RNA was expressed at similar levels in the esophagus, tongue, tonsil, floor of the mouth, and larynx. Genotyping revealed the presence of three variant reduced-activity UGT1A7 alleles in both Caucasians and African-Americans. Individuals with any of the predicted low-activity UGT1A7 genotypes had an increased risk of orolaryngeal cancer (odds ratio [OR] = 3.7; 95% confidence interval [CI] = 1.7 to 8.7) relative to subjects with the wild-type genotype. Both Caucasians and African-Americans with the low-activity genotypes had statistically significantly increased orolaryngeal cancer risk compared with Caucasians and African-Americans with the wild-type genotype (OR = 2.8 [95% CI = 1.1 to 7.6] and OR = 6.2 [95% CI = 1.2 to 31], respectively). For subjects with the predicted low-activity genotypes, the risks of oral cavity cancer (OR = 4.2; 95% CI = 1.7 to 10) and laryngeal cancer (OR = 3.7; 95% CI = 0.99 to 14) were similar. There was no association between UGT1A7 genotype and orolaryngeal cancer risk in never smokers, whereas subjects with predicted low-activity UGT1A7 genotypes who were light smokers (OR = 3.7; 95% CI = 1.1 to 12) or heavy smokers (OR = 6.1; 95% CI = 1.5 to 25) had an increased risk.

CONCLUSIONS

The tissue expression of UGT1A7 is consistent with the possibility of a physiologic role in orolaryngeal cancer. Variations in the UGT1A7 gene that reduce UGT1A7 activity may affect the risk of smoking-related orolaryngeal cancer.

摘要

背景

尿苷二磷酸葡萄糖醛酸基转移酶1A7（UGT1A7）可使多种烟草致癌物解毒。我们确定了UGT1A7在正常口咽组织中是否表达，以及UGT1A7等位基因变异是否与口咽癌风险相关。

方法

通过半定量逆转录-聚合酶链反应（PCR）测定正常口咽组织中UGT1A7的表达。从194例口咽癌病例受试者和388例按性别、年龄和种族匹配的对照受试者中分离颊细胞DNA，采用聚合酶链反应-限制性片段长度多态性联合等位基因鉴别分析进行UGT1A7基因分型。所有统计检验均为双侧检验。

结果

UGT1A7信使核糖核酸在食管、舌、扁桃体、口腔底部和喉部的表达水平相似。基因分型显示，白种人和非裔美国人中均存在三种活性降低的UGT1A7变异等位基因。与野生型基因型受试者相比，具有任何一种预测的低活性UGT1A7基因型的个体患口咽癌的风险增加（比值比[OR]=3.7；95%置信区间[CI]=1.7至8.7）。与野生型基因型的白种人和非裔美国人相比，低活性基因型的白种人和非裔美国人患口咽癌的风险在统计学上均显著增加（OR分别为2.8[95%CI=1.1至7.6]和OR=6.2[95%CI=1.2至31]）。对于具有预测的低活性基因型的受试者，口腔癌（OR=4.2；95%CI=1.7至10）和喉癌（OR=3.7；95%CI=0.99至14）的风险相似。从不吸烟者中UGT1A7基因型与口咽癌风险之间无关联，而轻度吸烟者（OR=3.7；95%CI=1.1至12）或重度吸烟者（OR=6.1；95%CI=1.5至25）中具有预测的低活性UGT1A7基因型的受试者风险增加。