MDM4基因rs1563828与乳腺癌发病风险及发病年龄的相关性研究

Correlation of polymorphism rs1563828 in MDM4 gene with breast cancer risk and onset age

目的探讨murine double minute4（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CC43．6％（44／101）、CT42．6％（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（）（。=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％C1：0．581～1．806，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。

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 2006 to 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：0. 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.