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.
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.
Authors: Bhramar Mukherjee; John Oliver Delancey; Leon Raskin; Jessica Everett; Joanne Jeter; Colin B Begg; Irene Orlow; Marianne Berwick; Bruce K Armstrong; Anne Kricker; Loraine D Marrett; Robert C Millikan; Hoda Anton Culver; Stefano Rosso; Roberto Zanetti; Peter A Kanetsky; Lynn From; Stephen B Gruber Journal: J Natl Cancer Inst Date: 2012-04-24 Impact factor: 13.506
Authors: Margaret A Tucker; David E Elder; Michael Curry; Mary C Fraser; Virginia Pichler; Deborah Zametkin; Xiaohong R Yang; Alisa M Goldstein Journal: J Invest Dermatol Date: 2018-02-08 Impact factor: 8.551
Authors: Giuseppe Palmieri; Maria Colombino; Milena Casula; Mario Budroni; Antonella Manca; Maria Cristina Sini; Amelia Lissia; Ignazio Stanganelli; Paolo A Ascierto; Antonio Cossu Journal: Melanoma Manag Date: 2015-05-18
Authors: Robert R McWilliams; Eric D Wieben; Kari G Chaffee; Samuel O Antwi; Leon Raskin; Olufunmilayo I Olopade; Donghui Li; W Edward Highsmith; Gerardo Colon-Otero; Lauren G Khanna; Jennifer B Permuth; Janet E Olson; Harold Frucht; Jeanine Genkinger; Wei Zheng; William J Blot; Lang Wu; Luciana L Almada; Martin E Fernandez-Zapico; Hugues Sicotte; Katrina S Pedersen; Gloria M Petersen Journal: Cancer Epidemiol Biomarkers Prev Date: 2018-07-23 Impact factor: 4.254