携带细胞周期蛋白依赖性激酶抑制剂2A（CDKN2A）始祖突变（p16-莱顿突变）的阳性黑色素瘤家族中，除黑色素瘤外其他癌症的发病风险增加。

Increased risk of cancer other than melanoma in CDKN2A founder mutation (p16-Leiden)-positive melanoma families.

作者信息

de Snoo Femke A, Bishop D Timothy, Bergman Wilma, van Leeuwen Inge, van der Drift Clasine, van Nieuwpoort Frans A, Out-Luiting Coby J, Vasen Hans F, ter Huurne Jeanet A C, Frants Rune R, Willemze Rein, Breuning Martijn H, Gruis Nelleke A

机构信息

Center for Human and Clinical Genetics, Leiden University Medical Center, Leiden, The Netherlands.

出版信息

Clin Cancer Res. 2008 Nov 1;14(21):7151-7. doi: 10.1158/1078-0432.CCR-08-0403.

DOI:10.1158/1078-0432.CCR-08-0403

PMID:18981015

Abstract

PURPOSE

We report the largest study to date analyzing the risk of cancers other than melanoma in melanoma families positive for the same CDKN2A mutation.

EXPERIMENTAL DESIGN

We studied family members of 22 families positive for the p16-Leiden founder mutation who had attended a surveillance clinic or were their close relatives. Within this cohort, observed and expected rates of cancer were computed by mutation status consisting of 221 (proven plus obligate) carriers, 639 (proven plus obligate) noncarriers, and 668 first-degree relatives whose carrier risk was estimated from the relationship to known carriers and the age and melanoma status of that person and their relatives.

RESULTS

Our analysis shows a relative risk (RR) of cancer other than melanoma and nonmelanoma skin cancer of 4.4 [95% confidence interval (95% CI), 3.3-5.6], predominantly attributable to the increased risk for pancreatic cancer (RR, 46.6; 95% CI, 24.7-76.4), but also for other cancers. We provide substantial proof for pancreatic cancer being a key component of the p16-Leiden phenotype. Inclusion of this cancer in a penetrance analysis leads to an estimated RR of pancreatic cancer for mutation carriers of 47.8 (95% CI, 28.4-74.7).

CONCLUSIONS

This study shows clear evidence of increased risk of cancers other than melanoma in CDKN2A families carrying the p16-Leiden mutation. Further research is necessary to determine if similar risks apply to families with CDKN2A mutations other than p16-Leiden.

摘要

目的

我们报告了迄今为止规模最大的一项研究，该研究分析了携带相同CDKN2A突变的黑色素瘤家族中除黑色素瘤以外的其他癌症风险。

实验设计

我们研究了22个携带p16-Leiden始祖突变的家族的家庭成员，这些家庭成员曾前往监测诊所就诊或为其近亲。在这个队列中，根据突变状态计算观察到的和预期的癌症发病率，突变状态包括221名（已证实加必然）携带者、639名（已证实加必然）非携带者以及668名一级亲属，其携带者风险是根据与已知携带者的关系以及该人及其亲属的年龄和黑色素瘤状态估算得出的。

结果

我们的分析显示，除黑色素瘤和非黑色素瘤皮肤癌以外的其他癌症的相对风险（RR）为4.4 [95%置信区间（95%CI），3.3 - 5.6]，主要归因于胰腺癌风险的增加（RR，46.6；95%CI，24.7 - 76.4），但其他癌症风险也有所增加。我们为胰腺癌是p16-Leiden表型的关键组成部分提供了充分证据。将这种癌症纳入外显率分析后，突变携带者的胰腺癌估计RR为47.8（95%CI，28.4 - 74.7）。