Smedby Karin Ekström, Lindgren Cecilia M, Hjalgrim Henrik, Humphreys Keith, Schöllkopf Claudia, Chang Ellen T, Roos Göran, Ryder Lars P, Falk Kerstin I, Palmgren Juni, Kere Juha, Melbye Mads, Glimelius Bengt, Adami Hans-Olov
Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Box 281, SE-171 77 Stockholm, Sweden.
Cancer Epidemiol Biomarkers Prev. 2006 Feb;15(2):258-65. doi: 10.1158/1055-9965.EPI-05-0583.
The reasons for the positive association between skin cancer and non-Hodgkin's lymphoma are not known but may be due to common susceptibility involving suboptimal DNA repair. Therefore, we investigated selected polymorphisms and haplotypes in three DNA repair genes, previously associated with skin cancer and DNA repair capacity, in risk of follicular lymphoma, including possible gene interaction with cigarette smoking and sun exposure. We genotyped 19 single nucleotide polymorphisms (SNP) in the ERCC2, XRCC1, and XRCC3 genes in 430 follicular lymphoma patients and 605 controls within a population-based case-control study in Denmark and Sweden. Odds ratios (OR) and 95% confidence intervals (95% CI) were calculated using unconditional logistic regression and haplotype associations were assessed with a global score test. We observed no associations between variation in the ERCC2 and XRCC1 genes and follicular lymphoma risk. In XRCC3, increased risk of follicular lymphoma was suggested for rare homozygotes of three SNPs [Rs3212024: OR, 1.8 (95% CI, 1.1-2.8); Rs3212038: OR, 1.5 (95% CI, 1.0-2.4); Rs3212090: OR, 1.5 (95% CI, 1.0-2.5)]. These results were strengthened in current cigarette smokers. However, evidence of differences in XRCC3 haplotype distributions between follicular lymphoma cases and controls was weak, both overall and in current smokers. We conclude that polymorphic variation in the XRCC3 gene, but not in ERCC2 or XRCC1, may be of importance for susceptibility to follicular lymphoma, perhaps primarily in current smokers. The link between skin cancer and follicular lymphoma is unlikely to be mediated through common variation in the studied DNA repair gene polymorphisms.
皮肤癌与非霍奇金淋巴瘤之间呈正相关的原因尚不清楚，但可能是由于涉及DNA修复欠佳的共同易感性。因此，我们研究了三个先前与皮肤癌及DNA修复能力相关的DNA修复基因中的特定多态性和单倍型，以探讨其在滤泡性淋巴瘤风险中的作用，包括与吸烟及日晒可能存在的基因相互作用。在丹麦和瑞典开展的一项基于人群的病例对照研究中，我们对430例滤泡性淋巴瘤患者及605名对照者的ERCC2、XRCC1和XRCC3基因中的19个单核苷酸多态性（SNP）进行了基因分型。使用非条件逻辑回归计算比值比（OR）及95%置信区间（95%CI），并通过全局评分检验评估单倍型关联。我们未观察到ERCC2和XRCC1基因变异与滤泡性淋巴瘤风险之间存在关联。在XRCC3基因中，三个SNP的罕见纯合子提示滤泡性淋巴瘤风险增加[Rs3212024：OR，1.8（95%CI，1.1 - 2.8）；Rs3212038：OR，1.5（95%CI，1.0 - 2.4）；Rs3212090：OR，1.5（95%CI，1.0 - 2.5）]。当前吸烟者的上述结果更为显著。然而，总体及当前吸烟者中，滤泡性淋巴瘤病例与对照者之间XRCC3单倍型分布差异的证据均较弱。我们得出结论，XRCC3基因的多态性变异而非ERCC2或XRCC1基因的变异，可能对滤泡性淋巴瘤的易感性具有重要意义，或许主要是在当前吸烟者中。皮肤癌与滤泡性淋巴瘤之间的联系不太可能通过所研究的DNA修复基因多态性的共同变异来介导。
