CAJ | 학술논문

目的探讨雌激素合成酶基因CYP17、CYP19和HSD17β1多态性与女性乳腺癌易感性的关系.方法采用配对病例对照研究,按年龄和绝经状态匹配病例和对照200对.通过问卷调查获取一般人口学特征、膳食因素和生殖生育因素等信息,用等位基因特异性聚合酶链反应(As-PCR)法,对CYP17(T1931C)、CYP19(Arg264Cys)和HSD17β1(A1954G)3个酶基因的单核苷酸多态性进行检测,用多因子降维法(MDR)模型分析基因一基因交互作用,根据MDR模型结果,利用非条件Logistic回归模型估计交互项及其他危险因素的危险度.结果 CYP17、CYP19和HSD17β易感基因型的独立主效应与乳腺癌的患病危险均无关联(OR≈1,均P>0.05).MDR模型中最佳正交互模型是CYP17(T1931C)和HSD17β1(A1954G)的联合作用,Sign检验P=0.05,检验样本平衡准确度为56.00%,交叉验证一致性为10/10.多因素非条件Logistic回归分析显示,调整BMI、服用雌激素、初产年龄、未足月产次和哺乳时间后,CYP17(T1931C)和HSD17β1(A1954G)的交互变量与乳腺癌的患病风险呈正关联(调整OR值为2.52,95%CI为1.54～4.11).结论 CYP17(T1931C)和HSD17β1(A1954G)基因多态性的交互作用可能增加乳腺癌的患病风险.
목적 탐토자격소합성매기인CYP17、CYP19화HSD17β1다태성여녀성유선암역감성적관계.방법 채용배대병례대조연구,안년령화절경상태필배병례화대조200대.통과문권조사획취일반인구학특정、선식인소화생식생육인소등신식,용등위기인특이성취합매련반응(As-PCR)법,대CYP17(T1931C)、CYP19(Arg264Cys)화HSD17β1(A1954G)3개매기인적단핵감산다태성진행검측,용다인자강유법(MDR)모형분석기인일기인교호작용,근거MDR모형결과,이용비조건Logistic회귀모형고계교호항급기타위험인소적위험도.결과 CYP17、CYP19화HSD17β역감기인형적독립주효응여유선암적환병위험균무관련(OR≈1,균P>0.05).MDR모형중최가정교호모형시CYP17(T1931C)화HSD17β1(A1954G)적연합작용,Sign검험P=0.05,검험양본평형준학도위56.00%,교차험증일치성위10/10.다인소비조건Logistic회귀분석현시,조정BMI、복용자격소、초산년령、미족월산차화포유시간후,CYP17(T1931C)화HSD17β1(A1954G)적교호변량여유선암적환병풍험정정관련(조정OR치위2.52,95%CI위1.54～4.11).결론 CYP17(T1931C)화HSD17β1(A1954G)기인다태성적교호작용가능증가유선암적환병풍험.
Objective To explore the relationship between the polymorphism of estrogen-biosynthesis genes (CYP17, CYP19, HSD17β1 ) 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 HSD17β1 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 HSD17β1 susceptible genotypes were not correlated to breast cancer ( 0R≈ 1, P >0.05 ) . The positive interaction effect between CYP17(T 1931C) and HSD17β1 (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 HSD17β1 (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 HSD17β1 (A1954G) polymorphism may jointly increase the risk of breast cancer.