The prevalence of CDKN2A germ-line mutations and relative risk for cutaneous malignant melanoma:: An international population-based study
The prevalence of CDKN2A germ-line mutations and relative risk for cutaneous malignant melanoma:: An international population-based study
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DOI：
10.1158/1055-9965.epi-06-0270
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发表时间：
2006-08-01
影响因子：
3.8
通讯作者：
Begg, Colin B.
中科院分区：
文献类型：
--
作者：
Berwick, Marianne;Orlow, Irene;Begg, Colin B.
在多病例家族研究中，CDKN 2A的生殖系突变已被确定为黑色素瘤的强风险因素。然而，在一般人群中评估他们患黑色素瘤的相对风险是困难的，因为他们很少发生。我们使用一种新的基于人群的病例对照研究设计来解决这个问题，其中“病例”有偶发的第二或更高级的黑色素瘤[多原发性黑色素瘤（MPM）]，“对照”有偶发的第一原发性黑色素瘤[单原发性黑色素瘤（SPM）]。参与者来自澳大利亚、加拿大、意大利和美国的九个地理区域。在1，189例MPM病例和2，424例SPM对照中，有资格并可用于分析，在调整年龄，性别，中心和已知表型风险因素后，患有功能突变且现有黑色素瘤诊断的患者中，后续黑色素瘤的相对风险估计为4.3（95%置信区间，2.3-7.7）。比值比根据所涉及的突变类型而显著变化。结果表明，人群中突变携带者的相对风险可能低于目前认为的，并且CDKN 2A基因的不同突变可能会导致黑色素瘤的风险显著不同。
Germ-line mutations of CDKN2A have been identified as strong risk factors for melanoma in studies of multiple-case families. However, an assessment of their relative risk for melanoma in the general population has been difficult because they occur infrequently. We addressed this issue using a novel population-based case-control study design in which "cases" have incident second- or higher-order melanomas [multiple primary melanoma (MPM)] and "controls" have incident first primary melanoma [single primary melanoma (SPM)]. Participants were ascertained from nine geographic regions in Australia, Canada, Italy, and United States. In the 1,189 MPM cases and 2,424 SPM controls who were eligible and available for analysis, the relative risk of a subsequent melanoma among patients with functional mutations who have an existing diagnosis of melanoma, after adjustments for age, sex, center, and known phenotypic risk factors, is estimated to be 4.3 (95% confidence interval, 2.3-7.7). The odds ratio varied significantly depending on the type of mutation involved. The results suggest that the relative risk of mutation carriers in the population may be lower than currently believed and that different mutations on the CDKN2A gene may confer substantially different risks of melanoma.