Increased Risk of Cancer Other Than Melanoma in CDKN2A Founder Mutation (p16-Leiden)-Positive Melanoma Families

被引:128
作者
de Snoo, Femke A. [3 ]
Bishop, D. Timothy [5 ]
Bergman, Wilma [1 ]
van Leeuwen, Inge [4 ]
van der Drift, Clasine [1 ,4 ]
van Nieuwpoort, Frans A. [1 ]
Out-Luiting, Coby J. [1 ]
Vasen, Hans F. [2 ,4 ]
ter Huurne, Jeanet A. C. [3 ]
Frants, Rune R. [3 ]
Willemze, Rein [1 ]
Breuning, Martijn H. [3 ]
Gruis, Nelleke A. [1 ,3 ]
机构
[1] Leiden Univ, Med Ctr, Dept Dermatol, NL-2333 ZC Leiden, Netherlands
[2] Leiden Univ, Med Ctr, Dept Gastroenterol, NL-2333 ZC Leiden, Netherlands
[3] Leiden Univ, Med Ctr, Ctr Human & Clin Genet, NL-2333 ZC Leiden, Netherlands
[4] Fdn Detect Hereditary Tumors, Leiden, Netherlands
[5] Univ Leeds, Leeds Inst Mol Med, Epidemiol & Biostat Sect, Leeds, W Yorkshire, England
关键词
D O I
10.1158/1078-0432.CCR-08-0403
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
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 non-melanoma 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% Cl, 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% Cl, 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.
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收藏
页码:7151 / 7157
页数:7
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