MDM4基因rs1563828与乳腺癌发病风险及发病年龄的相关性研究

摘要

Objective To explore effect of polymorphism rs1563828 (C ＞ T) in human murine double minute 4 gene ( MDM4 ) on genetic susceptibility for early-onset breast cancer and potential association with age of onset of breast cancer.Methods One hundred and twenty-four early-onset breast cancer patients (age ≤35 years at time of diagnosis) from independent families admitted from January 2006to June 2010 and 101 age-matched healthy control subjects were analyzed.Genotype analysis was conducted by polymerase chain reaction and then MALDI-TOF-MS assay.Association of genotype distribution and breast cancer risk was evaluated by x2 test.The odd-ratios (OR) and 95％ confidence intervals (CI) were calculated by unconditional Logistic regression model.The t test was used to compare the age and demographic differences among groups.Results The frequency of rs1563828 polymorphism genotypes in control group were CC 43.6％ (44/101),CT 42.6％ (43/101),TT 13.9％ ( 14/101 ),and in case group were 42.7％ ( 53/124 ),46.0％ ( 57/124 ),11.3％ ( 14/124 ),respectively.No significant difference (x2 =0.449,P =0.799) was reached by x2 test.rs1563828CT or TT genotype does not confer a significantly increased risk for breast cancer compared with CC genotype after adjusting for age,menarche in Logistic regression analysis ( OR =1.024,95％ CI:O.581-1.806,P =0.934).TT carriers were observed to develop breast cancer earlier than CC/CT carriers [( 30 ± 4 ) years vs.( 32 ± 3 ) years,P =0.028].Conclusions The rs1563828 (C ＞ T) polymorphism in MDM4 gene may not confer risk to breast cancer,especially for early-onset breast cancer patients.Homozygous TT of rs1563828 is associated with younger age to develop breast cancer.%目的 探讨murine double minute 4(MDM4)基因的单核苷酸多态性rs1563828(C＞T)在早发性乳腺癌人群中的分布、与乳腺癌发病风险的关联性及其与发病年龄的潜在关系.方法 本研究为病例-对照研究.采用飞行时间质谱分析法对124例早发性乳腺癌患者(发病年龄≤35岁)和101名健康对照者进行MDM4基因rs1563828(C＞T)基因型鉴定.采用x2检验比较基因型分布和发病风险的关系,应用非条件Logistic回归分析计算危险度,两组发病年龄比较采用t检验.结果 对照组MDM4基因rs1563828基因型的分布频率为CC 43.6％ (44/101)、CT 42.6％ (43/101)、TT13.9％(14/101),病例组则依次为42.7％(53/124)、46.0％(57/124)、11.3％(14/124)；两组差异无统计学意义(x2=0.449,P=0.799).Logistic回归分析表明,在早发性乳腺癌人群中,以rs1563828的CC野生基因型为参照,含T基因型(CT,TT)并未改变乳腺癌的发病危险(OR=1.024,95％ CI:0.581～1.806,P=0.934).在乳腺癌人群中,TT基因型携带者的发病年龄低于CT/CC基因型携带者[(30±4)岁比(32±3)岁,P=0.028].结论 MDM4基因rs1563828(C＞T)多态性可能与早发性乳腺癌人群的遗传易感性关联微弱,尚需进一步明确；其TT基因型可能是发病年龄提前的危险因素.