Savina Nataliya V, Nikitchenko Nataliya V, Kuzhir Tatyana D, Rolevich Alexander I, Krasny Sergei A, Goncharova Roza I
Institute of Genetics and Cytology, National Academy of Sciences of Belarus, 27 Akademicheskaya st., Minsk, 220072, Belarus.
N.N. Alexandrov National Cancer Center; Lesnoi 2, Minsk District, 223040, Belarus.
Curr Aging Sci. 2018;11(1):45-54. doi: 10.2174/1874609810666170707101548.
DNA helicases maintain genome stability, and their deficiency is associated with disorders resembling premature aging as well as contributes to carcinogenesis. Their functions are determined by the respective genes encoding nucleotide excision repair initiating proteins, e.g. XPD and CSB.
The present study aimed to investigate the influence of genetic variations in ERCC2/XPD (rs1799793, rs13181) and ERCC6/CSB (rs2228526, rs2228528) loci on lifespan and developing age-related bladder cancer focusing on homozygous wild type alleles.
The allelic variants were identified in 354 clinically healthy controls and 418 bladder cancer patients using the PCR-RFLP method.
The age-depended increase in frequencies of homozygous carriers of wild-type XPD 312Asp and XPD 751Lys alleles was observed among controls, especially among subjects over 80 years (r = 0.67, p = 0.012). The statistically significant correlation was also found between the frequency of homozygous wild type alleles at all tested loci and age in healthy population over 60 years (r = 0.35, p = 0.046) suggesting the relationship between lifespan and longevity, on one hand, and normal functioning of these genes and their products, on the other hand. Homozygous carriers of wild type alleles were less susceptible to bladder cancer, tumor invasion, increase in grade of malignancy and recurrence, but their effects were specific with respect to clinicopathological and lifestyle characteristics.
Homozygous wild type alleles encoding XPD and CSB proteins with optimal properties were shown to affect human lifespan, risk of developing bladder cancer, its progression and recurrence under certain conditions.
DNA解旋酶维持基因组稳定性，其缺陷与类似早衰的疾病相关，且会促进癌症发生。它们的功能由编码核苷酸切除修复起始蛋白的各自基因决定，例如XPD和CSB。
本研究旨在探讨ERCC2/XPD（rs1799793，rs13181）和ERCC6/CSB（rs2228526，rs2228528）基因座的遗传变异对寿命以及发生年龄相关性膀胱癌的影响，重点关注纯合野生型等位基因。
采用PCR-RFLP方法在354名临床健康对照者和418名膀胱癌患者中鉴定等位基因变异。
在对照者中观察到野生型XPD 312Asp和XPD 751Lys等位基因纯合携带者频率随年龄增加，尤其是在80岁以上的受试者中（r = 0.67，p = 0.012）。在60岁以上的健康人群中，所有测试基因座的纯合野生型等位基因频率与年龄之间也发现了统计学上的显著相关性（r = 0.35，p = 0.046），这表明一方面寿命和长寿与这些基因及其产物的正常功能之间存在关系。野生型等位基因的纯合携带者对膀胱癌、肿瘤侵袭、恶性程度增加和复发的易感性较低，但其影响在临床病理和生活方式特征方面具有特异性。
编码具有最佳特性的XPD和CSB蛋白的纯合野生型等位基因在某些条件下会影响人类寿命、患膀胱癌的风险、其进展和复发。
