Clinical Research Program, Department of Dermatology, Brigham and Women's Hospital, and Harvard Medical School, Boston, MA, USA.
DNA Repair (Amst). 2011 Jan 2;10(1):111-6. doi: 10.1016/j.dnarep.2010.08.005. Epub 2010 Sep 15.
Reduced DNA repair capacity has been proposed as a predisposing factor for melanoma. We comprehensively evaluated 1463 genetic variants across 60 DNA repair-related pathway genes in relation to melanoma risk in a nested case-control study of 218 melanoma cases (20% on head and neck) and 218 matched controls within the Nurses' Health Study (NHS). We then genotyped the two variants with the smallest P value in two replication sets: 184 melanoma cases (28% on head and neck) and 184 matched controls in the Health Professionals Follow-Up Study (HPFS); and 183 melanoma cases (10% on head and neck) and 183 matched controls in the NHS. The SNP rs3219125 in the PARP1 gene was significantly associated with melanoma risk in the discovery set (odds ratio (OR) 3.14; 95% confidence interval (CI) 1.70-5.80) and in the HPFS replication set (OR, 1.92; 95% CI, 1.05-3.54) but not in the NHS replication set (OR, 1.07; 95% CI, 0.58-1.97). In the joint analysis, the OR was 1.89 (95% CI, 1.34-2.68) for this polymorphism, and this increased risk was more pronounced among patients with lesions in head/neck (OR, 3.19; 95% CI, 1.77-5.73 for head/neck, and OR, 1.54; 95% CI, 1.03-2.30 for other sites, P value for heterogeneity test=0.036). Our findings suggest the possible involvement of the PARP1 variant in melanoma development, especially for sites with high sun exposure. Further work on fine-mapping and on the functional characterization of this and linked SNPs in this region is required.
据报道，DNA 修复能力下降可能是导致黑色素瘤的一个易感因素。我们在一项巢式病例对照研究中，对护士健康研究（NHS）中的 218 例黑色素瘤病例（20%位于头颈部）和 218 例匹配对照者（218 例匹配对照者）的 60 个与 DNA 修复相关通路基因中的 1463 个遗传变异进行了全面评估。然后，我们在健康专业人员随访研究（HPFS）中的两个复制集中对两个具有最小 P 值的变体进行了基因分型：184 例黑色素瘤病例（28%位于头颈部）和 184 例匹配对照者；以及 NHS 中的 183 例黑色素瘤病例（10%位于头颈部）和 183 例匹配对照者。PARP1 基因中的 SNP rs3219125 与发现集（比值比（OR）3.14；95%置信区间（CI）1.70-5.80）和 HPFS 复制集（OR，1.92；95%CI，1.05-3.54）中的黑色素瘤风险显著相关，但与 NHS 复制集（OR，1.07；95%CI，0.58-1.97）不相关。在联合分析中，该多态性的 OR 为 1.89（95%CI，1.34-2.68），对于头颈部病变的患者，这种风险增加更为明显（OR，3.19；95%CI，1.77-5.73 用于头颈部，OR，1.54；95%CI，1.03-2.30 用于其他部位，异质性检验 P 值=0.036）。我们的研究结果表明，PARP1 变异可能参与黑色素瘤的发生，尤其是在高阳光暴露部位。需要进一步进行精细作图和对该区域内该变体和相关 SNP 的功能特征进行研究。
