台湾女性宫颈上皮内瘤变中p53和XRCC1的基因多态性

Genetic polymorphism of p53 and XRCC1 in cervical intraepithelial neoplasm in Taiwanese women.

作者信息

Wu Ming-Tsang, Liu Chia-Ling, Ho Chi-Kung, Wu Trong-Neng

机构信息

Graduate Institute of Occupational Safety and Health, Department of Occupational Medicine, Kaohsiung Medical University, 100 Shih-Chuan 1st Road, Kaohsiung, Taiwan.

出版信息

J Formos Med Assoc. 2004 May;103(5):337-43.

PMID:15216398

Abstract

BACKGROUND AND PURPOSE

Many epidemiological studies have investigated the relationship between p53 codon 72 polymorphism and cervical cancer risk, but the findings are still conflicting. In contrast, data are lacking on the relationship between XRCC1 polymorphism and cervical neoplasm risk. This community-based nested case-control study examined the association between genetic polymorphisms of p53 codon 72 and XRCC1 codons 194, 280, and 399 and cervical intraepithelial neoplasm (CIN) susceptibility in Taiwanese women.

METHODS

Women living in Chiayi City, located in southwestern Taiwan, who had received Papanicolau (Pap) smear screening between October 1999 and December 2000 (n = 32,466) were included. Potential cases were women having lesions with cervical intraepithelial neoplasm II (CIN2) and over (> or = CIN2) reconfirmed by cervical biopsy. Potential controls (case:control = 1:2) were age matched (+/- 2 years) and residency matched women who had normal Pap smears. DNA samples were extracted from peripheral blood specimens and genetic polymorphisms of p53 and XRCC1 were determined by polymerase chain reaction-restriction fragment length polymorphism.

RESULTS

In total, 100 cases [97 high-grade squamous intraepithelial lesion (HSIL) and 3 invasive cancer] and 196 controls had complete demographic and clinical questionnaire data and data of analysis of XRCC1 polymorphism, whereas only 99 cases and 193 controls had complete data for p53 polymorphism. The frequency of pro/pro, pro/arg, and arg/arg in p53 codon 72 in cases was 15% (15/99), 58% (57/99), and 27% (27/99) and in controls was 17% (34/193), 48% (92/193), and 35% (67/193), respectively, which was not significantly different. The frequency of arg/arg, arg/gln, and gln/gln in XRCC1 codon 399 in cases was 54% (54/100), 38% (38/100), and 8% (8/100) and in controls was 58% (114/196), 37% (73/196), and 5% (9/196), respectively, which was not significantly different. No associations were found between XRCC1 codon 194 and 280 genotypes and HSIL risk. The joint effect of p53 and XRCC1 polymorphisms remained insignificant.

CONCLUSIONS

Our data suggest that p53 codon 72 and XRRC1 codon 194, 280 and 399 genotypes do not influence CIN risk in the Taiwanese population.

摘要

背景与目的

许多流行病学研究调查了p53密码子72多态性与宫颈癌风险之间的关系，但结果仍相互矛盾。相比之下，关于XRCC1多态性与宫颈肿瘤风险之间的关系的数据却很缺乏。这项基于社区的巢式病例对照研究，探讨了p53密码子72以及XRCC1密码子194、280和399的基因多态性与台湾女性宫颈上皮内瘤变（CIN）易感性之间的关联。

方法

纳入居住在台湾西南部嘉义市、在1999年10月至2000年12月期间接受过巴氏涂片筛查的女性（n = 32,466）。潜在病例为经宫颈活检再次确诊为宫颈上皮内瘤变II级（CIN2）及以上（≥CIN2）病变的女性。潜在对照（病例：对照 = 1:2）为年龄匹配（±2岁）且居住地区匹配、巴氏涂片结果正常的女性。从外周血标本中提取DNA样本，采用聚合酶链反应-限制性片段长度多态性方法测定p53和XRCC1的基因多态性。

结果

共有100例病例[97例高级别鳞状上皮内病变（HSIL）和3例浸润癌]和196例对照拥有完整的人口统计学和临床问卷数据以及XRCC1多态性分析数据，而只有99例病例和193例对照拥有完整的p53多态性数据。病例组中p53密码子72的pro/pro、pro/arg和arg/arg频率分别为15%（15/99）、58%（57/99）和27%（27/99），对照组分别为17%（34/193）、48%（92/193）和35%（67/193），差异无统计学意义。病例组中XRCC1密码子399的arg/arg、arg/gln和gln/gln频率分别为54%（54/100）、38%（38/100）和8%（8/100），对照组分别为58%（114/196）、37%（73/196）和5%（9/196），差异无统计学意义。未发现XRCC1密码子194和280基因型与HSIL风险之间存在关联。p53和XRCC1多态性的联合效应仍不显著。