Genetic variation in the base excision repair pathway and bladder cancer risk
Genetic variation in the base excision repair pathway and bladder cancer risk
复制标题
DOI：
10.1007/s00439-006-0294-y
复制
发表时间：
2007-04-01
期刊：
影响因子：
5.3
通讯作者：
Garcia-Closas, Montserrat
中科院分区：
文献类型：
--
作者：
Figueroa, Jonine D.;Malats, Nuria;Garcia-Closas, Montserrat
DNA修复基因的遗传多态性可能会影响DNA修复能力的个体差异并改变癌症风险。为了研究碱基切除修复（BER）途径中常见遗传变异与膀胱癌风险的关系，我们分析了12个BER基因（OGG 1，MUTYH，APEX 1，PARP 1，PARP 3，PARP 4，XRCC 1，POLB，POLD 1，PCNA，LIG 1和LIG 3）中的43个单核苷酸多态性（SNP）。使用来自西班牙膀胱癌研究的1，150例膀胱移行细胞癌和1，149例对照的基因型数据，我们估计了调整年龄，性别，地区和吸烟状况的比值比（OR）和95%置信区间（CI）。三个基因中的SNP与膀胱癌风险显着相关：8-oxoG DNA糖基化酶基因（OGG 1），聚（ADP-核糖）聚合酶家族成员1（PARP 1）和主要缺口填充聚合酶-β（POLB）。与普通纯合子相比，启动子区域（rs 125701）中OGG 1 SNP杂合或纯合变体的受试者膀胱癌风险显著降低：OR（95%CI）0.78（0.63-0.96）。与常见等位基因纯合子相比，功能性SNP PARP 1 rs 1136410（V762 A）或内含子SNP POLB rs3136717的杂合或纯合个体的风险增加：分别为1.24（1.02-1.51）和1.30（1.04-1.62）。总之，这项大型病例对照研究的数据表明膀胱癌风险与选定的BER SNP相关，这需要在其他研究人群中得到证实。
Genetic polymorphisms in DNA repair genes may impact individual variation in DNA repair capacity and alter cancer risk. In order to examine the association of common genetic variation in the base-excision repair (BER) pathway with bladder cancer risk, we analyzed 43 single nucleotide polymorphisms (SNPs) in 12 BER genes (OGG1, MUTYH, APEX1, PARP1, PARP3, PARP4, XRCC1, POLB, POLD1, PCNA, LIG1, and LIG3). Using genotype data from 1,150 cases of urinary bladder transitional cell carcinomas and 1,149 controls from the Spanish Bladder Cancer Study we estimated odds ratios (ORs) and 95% confidence intervals (CIs) adjusting for age, gender, region and smoking status. SNPs in three genes showed significant associations with bladder cancer risk: the 8-oxoG DNA glycosylase gene (OGG1), the Poly (ADP-ribose) polymerase family member 1 (PARP1) and the major gap filling polymerase-beta (POLB). Subjects who were heterozygous or homozygous variant for an OGG1 SNP in the promoter region (rs125701) had significantly decreased bladder cancer risk compared to common homozygous: OR (95%CI) 0.78 (0.63-0.96). Heterozygous or homozygous individuals for the functional SNP PARP1 rs1136410 (V762A) or for the intronic SNP POLB rs3136717 were at increased risk compared to those homozygous for the common alleles: 1.24 (1.02-1.51) and 1.30 (1.04-1.62), respectively. In summary, data from this large case-control study suggested bladder cancer risk associations with selected BER SNPs, which need to be confirmed in other study populations.