Does MC1R Genotype Convey Information About Melanoma Risk Beyond Risk Phenotypes?
Does MC1R Genotype Convey Information About Melanoma Risk Beyond Risk Phenotypes?
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DOI：
10.1002/cncr.24994
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发表时间：
2010-05-15
期刊：
影响因子：
6.2
通讯作者：
Rebbeck, Timothy R.
中科院分区：
文献类型：
--
作者：
Kanetsky, Peter A.;Panossian, Saarene;Rebbeck, Timothy R.
背景：开展了一项研究以描述美国人群中黑素皮质素1受体（MC1R）变异体与黑色素瘤的关联，并调查遗传风险是否因色素沉着特征和日晒措施而改变。
方法：黑色素瘤患者（n = 960）和对照组（n = 396）通过结构化问卷自我报告表型特征和日晒情况，并接受皮肤检查。使用逻辑回归来估计高风险和低风险MC1R变异体与黑色素瘤的关联，包括总体情况以及在表型和日晒分层内的情况。对已发表研究的结果进行了荟萃分析。
结果：携带2个低风险或任何高风险MC1R变异体与黑色素瘤风险增加相关（比值比[OR]分别为1.7，95%置信区间[CI]为1.0 - 2.8；以及OR为2.2，95%CI为1.5 - 3.0）。然而，在具有保护性表型且日晒有限的个体中，风险更强或仅限于这些个体，例如那些反复日晒后容易晒黑的人（OR为2.4，95%CI为1.6 - 3.6）、头发颜色深的人（OR为2.4，95%CI为1.5 - 3.6）或眼睛颜色深的人（OR为3.2，95%CI为1.8 - 5.9）。我们注意到在那些没有雀斑、在首次强烈夏日阳光照射后会晒黑、报告很少或平均的休闲或职业日晒量，或报告没有晒伤事件的人中，黑色素瘤风险增加的模式相同。对已发表文献的荟萃分析支持了这些发现。
结论：这些数据表明，MC1R基因型为那些仅根据其表型或暴露情况不会被确定为高风险的个体提供了有关黑色素瘤风险的信息。《癌症》2010年；116:2416 - 28。（C）2010美国癌症协会
BACKGROUND: A study was carried out to describe associations of MC1R variants and melanoma in a US population and to investigate whether genetic risk is modified by pigmentation characteristics and sun exposure measures METHODS: Melanoma patients (n = 960) and controls (n = 396) self-reported phenotypic characteristics and sun exposure via structured questionnaire and underwent a skin examination Logistic regression was used to estimate associations of high- and low-risk MC1R variants and melanoma, overall and within phenotypic and sun exposure strata A meta-analysis of results from published studies was undertaken RESULTS: Carriage of 2 low-risk or any high-risk MC1R variants was associated with increased risk of melanoma (odds ratio [OR], 17, 95% confidence interval [CI], 10-2 8, and OR, 2 2, 95% Cl, 1 5-3 0, respectively) However, risk was stronger in or limited to individuals with protective phenotypes and limited sun exposure, such as those who tanned well after repeated sun exposure (OR, 2 4, 95% Cl, 1 6-3 6), had dark hair (OR, 2 4, 95% Cl, 1 5-3 6), or had dark eyes (OR, 3 2, 95% Cl, 18-5 9) We noted this same pattern of increased melanoma risk among persons who did not freckle, tanned after exposure to first strong summer sun, reported little or average recreational or occupational sun exposure, or reported no sun burning events Meta-analysis of published literature supported these findings CONCLUSIONS: These data indicate that MC1R genotypes provide information about melanoma risk in those individuals who would not be identified as high risk based on their phenotypes or exposures alone Cancer 2010;116:2416-28. (C) 2010 American Cancer Society