PALB2基因遗传多态性在早发性乳腺癌中的作用

Role of three polymorphism in PALB2 gene on early onset breast cancer

背景与目的:PALB2基因是新近发现的乳腺癌易感基因,其多个遗传单核苷酸多态性(SNP)可能与乳腺癌发病风险有关,本研究探讨PALB2基因rs249954、rs447529及rs16940342多态性在福建早发性乳腺癌人群中的分布及其与乳腺癌发病风险的相关性。方法:对124例早发性乳腺癌患者(年龄≤35岁)和101例健康女性进行PALB2基因rs249954、rs447529及rs16940342 PCR扩增,并采用基质辅助激光解吸电离飞行时间质谱分析(MALDI-TOF-MS)法鉴定其基因型,比较各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(OR)及95%CI。结果:PALB2基因rs249954、rs447529及rs16940342多态性基因型在病例组中的分布频率与对照组的分布频率均未见明显差异(P>0.05)。Logistic回归分析表明,在早发性乳腺癌人群中,以rs249954的CC基因型、rs447529 CC基因型及rs16940342 AA基因型为参照,各基因多态性位点的其他基因型,均未能显著改变乳腺癌的发病危险(P>0.05)。各基因型风险比分别为1.061(rs249954 TT vs CC),0.793(rs447529 GG vs CC)以及0.921(rs16940342 GG vs AA)。结论:PALB2基因rs249954、rs447529及rs16940342多态性可能与福建地区汉族人群早发性乳腺癌的遗传易感性无关,作为低外显率的乳腺癌易感基因位点和未来临床基因筛查的候选指标尚需谨慎。

Background and purpose：PALB2 has been recently identified as a possible susceptibility gene for breast cancer.Some polymorphisms in PALB2 have been explored in sporadic breast cancer population and given inconsistent results.This study investigated the effects of three polymorphisms（rs249954,rs447529 and rs16940342） on PALB2 gene in terms of genetic susceptibility for the early-onset breast cancer Methods：One hundred and twenty-four early-onset breast cancer patients（age≤35yrs at diagnosis） from independent families and 101 healthy control subjects of the same ages were analyzed.Genotype analysis was conducted using polymerase chain reaction（PCR） and then MALDI-TOF-MS assay.The odd-ratios（OR） and 95% of the confidence intervals（CI） were calculated using the unconditional logistic regression model.Results：The frequency of rs249954,rs447529 and rs16940342 polymorphism genotypes in the case group and control group were not significantly different,respectively（P0.05）.Under a logistic regression analysis,rs249954 CT or TT,rs447529 GG or CG and rs16940342 GA or GG genotype did not confer a significantly increased risk for breast cancer when compared with the rs249954 CC,rs447529 CC and rs16940342 AA genotype,respectively（P0.05）.The OR were 1.061 for rs249954 TT vs CC,0.793 for rs447529 GG vs CC and 0.921 for rs16940342 GG vs AA,respectively.Conclusion：rs249954,rs447529 and rs16940342 polymorphism in the PALB2 gene do not contribute to risk of breast cancer,especially for early-onset breast cancer patients.Considering these polymorphisms as candidates for low penetrance breast cancer gene susceptibility needs to be further investigated.