Suerink Manon, van der Klift Heleen M, Ten Broeke Sanne W, Dekkers Olaf M, Bernstein Inge, Capellá Munar Gabriel, Gomez Garcia Encarna, Hoogerbrugge Nicoline, Letteboer Tom G W, Menko Fred H, Lindblom Annika, Mensenkamp Arjen, Moller Pal, van Os Theo A, Rahner Nils, Redeker Bert J W, Olderode-Berends M J W, Spruijt Liesbeth, Vos Yvonne J, Wagner Anja, Morreau Hans, Hes Frederik J, Vasen Hans F A, Tops Carli M, Wijnen Juul T, Nielsen Maartje
Department of Clinical Genetics, Leiden University Medical Center, Leiden, The Netherlands.
Department of Human Genetics, Leiden University Medical Center, Leiden, The Netherlands.
Genet Med. 2016 Apr;18(4):405-9. doi: 10.1038/gim.2015.83. Epub 2015 Jun 25.
Lynch syndrome (LS), a heritable disorder with an increased risk of primarily colorectal cancer (CRC) and endometrial cancer (EC), can be caused by mutations in the PMS2 gene. We wished to establish whether genotype and/or parent-of-origin effects (POE) explain (part of) the reported variability in severity of the phenotype.
European PMS2 mutation carriers (n = 381) were grouped and compared based on RNA expression and whether the mutation was inherited paternally or maternally.
Mutation carriers with loss of RNA expression (group 1) had a significantly lower age at CRC diagnosis (51.1 years vs. 60.0 years, P = 0.035) and a lower age at EC diagnosis (55.8 years vs. 61.0 years, P = 0.2, nonsignificant) compared with group 2 (retention of RNA expression). Furthermore, group 1 showed slightly higher, but nonsignificant, hazard ratios (HRs) for both CRC (HR: 1.31, P = 0.38) and EC (HR: 1.22, P = 0.72). No evidence for a significant parent-of-origin effect was found for either CRC or EC.
PMS2 mutation carriers with retention of RNA expression developed CRC 9 years later than those with loss of RNA expression. If confirmed, this finding would justify a delay in surveillance for these cases. Cancer risk was not influenced by a parent-of-origin effect.Genet Med 18 4, 405-409.
林奇综合征（LS）是一种遗传性疾病，主要增加结直肠癌（CRC）和子宫内膜癌（EC）的发病风险，可由PMS2基因突变引起。我们希望确定基因型和/或亲本来源效应（POE）是否能解释（部分）所报道的表型严重程度的变异性。
根据RNA表达情况以及突变是父系遗传还是母系遗传，对欧洲的381名PMS2突变携带者进行分组和比较。
与第2组（RNA表达保留）相比，RNA表达缺失的突变携带者（第1组）结直肠癌诊断时的年龄显著更低（51.1岁对60.0岁，P = 0.035），子宫内膜癌诊断时的年龄也更低（55.8岁对61.0岁，P = 0.2，无统计学意义）。此外，第1组在结直肠癌（风险比：1.31，P = 0.38）和子宫内膜癌（风险比：1.22，P = 0.72）方面的风险比略高，但无统计学意义。未发现结直肠癌或子宫内膜癌存在显著亲本来源效应的证据。
RNA表达保留的PMS2突变携带者患结直肠癌的时间比RNA表达缺失的携带者晚9年。如果得到证实，这一发现将证明对这些病例的监测可以延迟。癌症风险不受亲本来源效应的影响。《遗传医学》18卷4期，405 - 409页。
