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编者按：曾经有人看到我们发布的文章后，留言称自己的大姑和二姨有乳腺癌，询问自己得乳腺癌的概率有多少？其实这个问题就好比，自己的大姑和二姨考上了清华北大，询问自己考上清华北大的概率有多少？人群的发病率与升学率一样，对于个人而言没有意义，需要个体化分析。即使知道母亲的乳腺癌风险，也不代表女儿的乳腺癌风险也是如此。 2018年6月19日，欧洲乳腺癌专科学会《乳腺》在线发表法国里昂癌症研究中心、莱昂贝拉尔癌症中心、里昂高等师范学院、斯特拉斯堡大学医院、保罗斯特劳斯癌症中心的研究报告，探讨了多基因风险评分用于大样本人群的情况，并且通过风险评分对子代传递进行量化。 该研究根据1000个基因组数据与乳腺癌风险相关的159个单核苷酸多态性等位基因率，计算了10万人的乳腺癌风险评分。选择两个“父母”模拟其等位基因随机传递给10万个“女儿”，将人群按风险评分进行分组，比较母亲与女儿人群的平均风险评分，得出人群水平整体关系信息。通过分析母亲各组风险评分内的女儿风险评分分布情况，评估个体水平传递情况。 结果发现，母亲、女儿的平均风险评分分别为85.1±7.5、85.0±7.5（平均绝对差：0.02，P=0.48）。 当母亲到女儿的风险评分传递分析到特定风险评分范围时，所有风险评分差异可见统计学意义（P=0.001、<2.2×10-16）。 因此，在人群水平，母亲与女儿根据基因变异得出的乳腺癌风险评分之间存在相关性；在个体水平，母亲与女儿的乳腺癌风险评分相关性高度可变，仅仅根据母亲的乳腺癌风险评分，无法提供关于子代乳腺癌预防和筛查的信息。该研究结果表明，根据多基因风险评分，个体乳腺癌风险各不相同，需要对于每位个体进行乳腺癌风险评分。 Breast. 2018 Jun 19;41:14-18. [Epub ahead of print] Transmission of breast cancer polygenic risk based on single nucleotide polymorphisms. David G. Cox, Pierre-Etienne Heudel, Julie Henry, Xavier Pivot. INSERM U1052, Lyon, France; Centre Léon Bérard, Lyon, France; Ecole Normale Superieur de Lyon, Lyon Cedex, France; Centre Paul Strauss, Porte de l'Hopital Strasbourg, France. HIGHLIGHTS
AIM: The goal of the present study was to further refine how polygenic risk scores may be used in a large population and to quantify the transmission of risk score through generations. METHODS: Allele frequencies from the 1000 Genomes data for 159 single nucleotide polymorphisms associated with breast cancer risk were used. A breast cancer risk score was calculated among 100,000 people. Choosing two "parents" and the alleles they transmit at random, 100,000 "daughters" were simulated. The population was divided by deciles of risk score. Comparing mean risk score in the mother and daughter populations provided information regarding the general relationship at a population level. By examining the distribution of daughter's risk score within each decile of maternal risk score, the transmission was evaluated at the subject level. RESULTS: Mean values of risk score were 85.1 (St Dev=7.5) and 85.0 (St Dev=7.5) for the populations of mothers and daughters, respectively (mean absolute difference=0.02, p=0.48). When examining the transmission of risk score from mothers to daughters in specific deciles of risk, statistically significant differences were observed in all deciles (ranged between 0.001 and<2.2×10-16). CONCLUSION: The relationship at the subject level will not provide information regarding prevention and screening of offspring based on the knowledge of parents' risk score alone. The present results show that risk estimation by polygenic risk scores is personal, and evaluation of risk score is required for each individual. DOI: 10.1016/j.breast.2018.06.006 |
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