Hüttelová R, Kleibl Z, Rezátová J, Krutílková V, Foretová L, Novotný J, Kotlas J, Zikán M, Pohlreich P
IVF-Institut s. r o, Plzen.
Klin Onkol. 2009;22 Suppl:S69-74.
Carriers of hereditary mutations in cancer susceptibility genes represent a limited but high-risk population characterized by a high probability of cancer development, frequently with its manifestation in early age and with a 50% chance of pathogenic allele inheritance by offspring. In case of monogenic disorders, preimplantation genetic diagnosis (PGD) could be used for characterization of the DNA region affected by pathogenic mutation in the early stages of an embryo created by in vitro fertilization (IVF). Therefore, the transfer of unaffected embryos could be performed based on the results of PGD genotyping, enabling the development of offspring not carrying the pathogenic alteration.
Here we present the consensus of the collaborative group of the Society for Medical Genetics, the Czech Society for Oncology and other professionals for use of PGD in the Czech Republic for carriers of mutations in cancer susceptibility genes. We address the conditions, prerequisites, and limits of practical application of this method. We also point out specific issues of ovarian hyperstimulation in carriers of mutations in BRCA1, BRCA2, and p53, anticipating the increased risk of hormonally dependent breast and ovarian cancers development.
We assume that a narrow but non-negligible subgroup of cancer susceptibility gene mutation carriers may benefit from PGD.They are mainly individuals deciding to undergo IVF and PGD recruited from mutation carriers with extreme concerns about transmitting the mutation to their children. The PGD in these individuals should be managed by a closely cooperating multidisciplinary team of professionals responsible for indication of PGD, giving complete information regarding the IVF and PGD procedures including their limits, evaluating individual risks and performing instrumental and laboratory procedures with respect to up-to-date good laboratory and clinical practice.
癌症易感基因遗传性突变的携带者是一个数量有限但风险很高的群体，其特征是患癌概率高，常在早年发病，且后代有50%的概率遗传致病等位基因。对于单基因疾病，植入前基因诊断（PGD）可用于在体外受精（IVF）产生的胚胎早期阶段鉴定受致病突变影响的DNA区域。因此，可根据PGD基因分型结果移植未受影响的胚胎，从而孕育出不携带致病改变的后代。
本文展示了医学遗传学学会、捷克肿瘤学会及其他专业人士组成的协作组对于在捷克共和国将PGD用于癌症易感基因突变携带者的共识。我们阐述了该方法实际应用的条件、前提和局限性。我们还指出了携带BRCA1、BRCA2和p53基因突变者卵巢过度刺激的具体问题，预计其患激素依赖性乳腺癌和卵巢癌的风险会增加。
我们认为癌症易感基因突变携带者中一个规模小但不可忽视的亚组可能会从PGD中受益。他们主要是那些决定接受IVF和PGD的个体，这些个体来自对将突变遗传给子女极为担忧的突变携带者。这些个体的PGD应由一个密切合作的多学科专业团队管理，该团队负责PGD的指征，提供有关IVF和PGD程序（包括其局限性）的完整信息，评估个体风险，并按照最新的良好实验室和临床实践进行仪器和实验室操作。
