Azevedo Ana P, Silva Susana N, De Lima João P, Reichert Alice, Lima Fernando, Júnior Esmeraldina, Rueff José
Centre for Toxicogenomics and Human Health (ToxOmics), Genetics, Oncology and Human Toxicology, NOVA Medical School, Faculty of Medical Sciences, NOVA University of Lisbon, 1169-056 Lisbon, Portugal.
Department of Clinical Pathology, Hospital of São Francisco Xavier, West Lisbon Hospital Centre, 1449-005 Lisbon, Portugal.
Oncol Lett. 2017 Jun;13(6):4641-4650. doi: 10.3892/ol.2017.6065. Epub 2017 Apr 21.
The role of base excision repair (BER) genes in Philadelphia-negative (PN)-myeloproliferative neoplasms (MPNs) susceptibility was evaluated by genotyping eight polymorphisms [apurinic/apyrimidinic endodeoxyribonuclease 1, mutY DNA glycosylase, earlier mutY homolog () (MUTYH), 8-oxoguanine DNA glycosylase 1, poly (ADP-ribose) polymerase (PARP) 1, PARP4 and X-ray repair cross-complementing 1 (XRCC1)] in a case-control study involving 133 Caucasian Portuguese patients. The results did not reveal a correlation between individual BER polymorphisms and PN-MPNs when considered as a whole. However, stratification for essential thrombocythaemia revealed i) borderline effect/tendency to increased risk when carrying at least one variant allele for XRCC1_399 single-nucleotide polymorphism (SNP); ii) decreased risk for Janus kinase 2-positive patients carrying at least one variant allele for XRCC1_399 SNP; and iii) decreased risk in females carrying at least one variant allele for MUTYH SNP. Combination of alleles demonstrated an increased risk to PN-MPNs for one specific haplogroup. These findings may provide evidence for gene variants in susceptibility to MPNs. Indeed, common variants in DNA repair genes may hamper the capacity to repair DNA, thus increasing cancer susceptibility.
在一项涉及133名葡萄牙白种人的病例对照研究中，通过对8种多态性（脱嘌呤/脱嘧啶内切脱氧核糖核酸酶1、mutY DNA糖基化酶、早期mutY同源物（MUTYH）、8-氧代鸟嘌呤DNA糖基化酶1、聚（ADP-核糖）聚合酶（PARP）1、PARP4和X射线修复交叉互补蛋白1（XRCC1））进行基因分型，评估碱基切除修复（BER）基因在费城染色体阴性（PN）骨髓增殖性肿瘤（MPN）易感性中的作用。总体来看，结果并未显示个体BER多态性与PN-MPN之间存在相关性。然而，对原发性血小板增多症进行分层分析发现：i）当携带至少一个XRCC1_399单核苷酸多态性（SNP）的变异等位基因时，存在临界效应/风险增加趋势；ii）携带至少一个XRCC1_399 SNP变异等位基因的Janus激酶2阳性患者风险降低；iii）携带至少一个MUTYH SNP变异等位基因的女性风险降低。等位基因组合显示，一种特定单倍型组患PN-MPN的风险增加。这些发现可能为MPN易感性中的基因变异提供证据。事实上，DNA修复基因中的常见变异可能会妨碍DNA修复能力，从而增加癌症易感性。
