DNA repair, dysplastic nevi, and sunlight sensitivity in the development of cutaneous malignant melanoma
DNA repair, dysplastic nevi, and sunlight sensitivity in the development of cutaneous malignant melanoma
复制标题
DOI：
10.1093/jnci/94.2.94
复制
发表时间：
2002-01-16
影响因子：
10.3
通讯作者：
Grossman, L
中科院分区：
文献类型：
--
作者：
Landi, MT;Baccarelli, A;Grossman, L
背景：紫外线照射与皮肤恶性黑色素瘤(CMM)相关。在哺乳动物细胞中，紫外线辐射导致DNA损伤，这种损伤可以通过核苷酸切除修复系统来修复。我们设计了这项病例对照研究，以确定DNA修复能力(DRC)是否与CMM的风险相关，并确定在黑色素瘤的发生过程中可能与DRC相互作用的风险因素。方法：用宿主细胞复活法测定淋巴细胞的全局DRC。采用多元回归模型对数据进行分析。所有的统计检验都是双面的。结果：132例偶发性黑色素瘤患者和145例年龄、性别匹配的对照组均可测定DRC。未发现黑色素瘤风险与DRC之间有统计学意义的关联(优势比[OR]=1.0；95%可信区间[CI]=0.6至1.7，调整了年龄、性别、淋巴细胞活性和样本储存时间)。然而，DRC对晒黑能力低或发育不良痣的个体的CMM风险有很大影响。制革能力低、DRC低的个体患CMM的风险(OR=8.6；95%CI=2.7~27.5)高于制革能力高、DRC高的个体。同样，发育不良痣和低DRC个体的相对危险度(OR=6.7；95%CI=2.4~18.6)也高于无发育不良痣且DRC高的个体。患有发育不良痣和高DRC的受试者有中等风险。似然比检验显示DRC与晒黑反应(P=.001)以及DRC与发育不良的痣状态(P=0.04)之间存在统计学意义上的交互作用，它们与CMM风险独立相关。结论：DRC可以在存在其他强烈的危险因素的情况下改变黑色素瘤的风险，如晒黑能力低和发育不良的痣的存在。在没有这些危险因素的受试者中，黑色素瘤的发生似乎与DRC无关。
Background: Exposure to UV radiation is associated with cutaneous malignant melanoma (CMM). In mammalian cells, UV radiation induces DNA damage that can be repaired by the nucleotide excision repair system. We designed this case-control study to determine whether DNA repair capacity (DRC) is associated with the risk of CMM and to identify risk factors that may interact biologically with DRC in the development of melanoma. Methods: Global DRC was measured in lymphocytes with the host-cell reactivation assay. Data were analyzed by use of multiple regression models. All statistical tests were two-sided. Results: DRC could be determined for 132 case patients with incident melanoma and for 145 age- and sex-matched control subjects. No statistically significant association between melanoma risk and DRC by itself was found (odds ratio [OR] = 1.0; 95% confidence interval [CI] = 0.6 to 1.7, adjusted for age, sex, lymphocyte viability, and sample storage time). DRC, however, strongly influenced CMM risk in individuals with a low tanning ability or dysplastic nevi. Individuals with a low tanning ability and a low DRC had a higher risk for CMM (OR = 8.6; 95% CI = 2.7 to 27.5) than individuals with a higher tanning ability and a high DRC. Likewise, individuals with dysplastic nevi and a low DRC had a higher relative risk (OR = 6.7; 95% CI = 2.4 to 18.6) than those lacking dysplastic nevi and having a high DRC. Subjects with dysplastic nevi and a high DRC had an intermediate risk. A likelihood-ratio test gave statistically significant interactions between DRC and tanning response (P =.001) and between DRC and dysplastic nevus status (P =.04), which were independently associated with CMM risk. Conclusions: DRC may modify the risk for melanoma in the presence of other strong risk factors, such as a low tanning ability and the presence of dysplastic nevi. The occurrence of melanoma in subjects without these risk factors appears to be independent of DRC.