雌激素生物合成基因（CYP17、CYP19、HSD17β1）多态性与乳腺癌的关系

[Relationship between estrogen-biosynthesis gene (CYP17, CYP19, HSD17beta1) polymorphisms and breast cancer].

作者信息

Wang Yuan-ping, Li Hui, Li Jia-yuan, Yuan Ping, Yang Fei, Lei Fang-ming, Pang Yi, Guo Jie

机构信息

West-China School of Public Health, Sichuan University, Chengdu 610041, China.

出版信息

Zhonghua Zhong Liu Za Zhi. 2009 Dec;31(12):899-903.

PMID:20193327

Abstract

OBJECTIVE

To explore the relationship between the polymorphism of estrogen-biosynthesis genes (CYP17, CYP19, HSD17beta1) and risk of breast cancer.

METHODS

A matched case-control study was designed. From May 2007 to July 2008, 200 pairs of subjects with and without breast cancer were enrolled, who were matched by age and menstruation status. Demographical characteristics, dietary factors and reproductive factors were investigated by questionnaire. CYP17 locus 1931 (T-->C), CYP19 codon 264 (Arg-->Cys) and HSD17beta1 locus 1954 (A-->G) were identified by AS-PCR (allele-specific PCR). The gene-gene interaction were analyzed with the MDR model (multifactor dimensionality reduction). Based on the results of MDR model, an unconditional logistic regression model was simulated to estimate the ORs of interaction factors and other risk factors.

RESULTS

The main effect of CYP17, CYP19 and HSD17beta1 susceptible genotypes were not correlated to breast cancer (OR approximately 1, P > 0.05). The positive interaction effect between CYP17 (T 1931C) and HSD17beta1 (A1954G) was discovered by MDR model with a statistically significant difference (Sign test, P = 0.05). The model's testing balance accuracy was 56.00%, and crossing validation consistency was 10/10. Multivariable unconditional logistic regression showed that after adjusting BMI, intake of estrogen, age of first birth, number of abortion and period of breast feeding, the interaction item of CYP17 (T1931C) and HSD17beta1 (A1954G) was strongly and positively correlated to breast cancer (OR = 2.52, 95%CI = 1.54 to 4.11).

CONCLUSION

The estrogen-biosynthesis genes CYP17 (T1931C) and HSD17beta1 (A1954G) polymorphism may jointly increase the risk of breast cancer.

摘要

目的

探讨雌激素生物合成基因（CYP17、CYP19、HSD17β1）多态性与乳腺癌风险之间的关系。

方法

设计一项匹配病例对照研究。2007年5月至2008年7月，纳入200对有乳腺癌和无乳腺癌的受试者，按年龄和月经状态进行匹配。通过问卷调查人口统计学特征、饮食因素和生殖因素。采用等位基因特异性PCR（AS-PCR）鉴定CYP17基因座1931（T→C）、CYP19密码子264（Arg→Cys）和HSD17β1基因座1954（A→G）。用多因素降维法（MDR）分析基因-基因相互作用。基于MDR模型结果，模拟无条件逻辑回归模型以估计相互作用因素和其他风险因素的比值比（OR）。

结果

CYP17、CYP19和HSD17β1易感基因型的主要效应与乳腺癌无关（OR约为1，P>0.05）。MDR模型发现CYP17（T1931C）和HSD17β1（A1954G）之间存在正向相互作用效应，差异有统计学意义（符号检验，P = 0.05）。该模型的检验平衡准确率为56.00%，交叉验证一致性为10/10。多变量无条件逻辑回归显示，在调整体重指数、雌激素摄入量、初产年龄、流产次数和母乳喂养时间后，CYP17（T1931C）和HSD17β1（A1954G）的相互作用项与乳腺癌呈强正相关（OR = 2.52，95%CI = 1.54至4.11）。