Penetrance of CDKN2A mutations estimated using population-based Australian families

Mark Jenkins, Anne Cust, Daniel Schmidt, Enes Makalic, Elizabeth Holland, Helen Scmid, Richard Kefford, Graham Giles, Armstrong Bruce, Joanne Aitkin, Graham Mann, John Hopper, Australian Melanoma Family Study

Research output: Contribution to journalMeeting abstractpeer-review


Background: CDKN2A gene mutations increase risk ofmelanoma (67% by age 80 when using multiple-casefamilies, and 28% by age 80 when using population-basedfamilies with unverified melanoma histories.Methods: The Australian Melanoma Family Study, apopulation-based case-control-family study, included pro-bands with incident cutaneous melanoma diagnosedbefore age 40 recruited from Brisbane, Sydney andMelbourne and their first- and second-degree relatives.We identified 12 probands with pathogenic or suspectedpathogenic CDKN2A mutations. The hazard ratio (HR) ofmelanoma incidence for carriers relative to that for thegeneral population, were estimated using a modifiedsegregation analysis that incorporates both genotypedand ungenotyped relatives and conditions on ascertain-ment to produce unbiased estimates.Results:The HR for reported melanoma was greater forfemales than males (HR 5 34.2 and 9.9, respectively;P 5 0.02). Combining males and females, the penetranceof melanoma for CDKN2A mutation carriers was 60% (95% CI: 43 to 77%) by age 80 (females 70%, males 43%). TheHRs for confirmed melanoma was 8.4 for males andfemales combined (c.f. 19.5 for reported melanoma).Conclusion: Our population-based estimates of melanomarisk which apply to the mutations identified in early-onsetcases of melanoma, appear to be higher than previouspopulation-based estimates from studying the families ofcases unselected for age at onset and were higher forfemales than males.
Original languageEnglish
Article number203
Pages (from-to)811-812
Number of pages2
JournalGenetic Epidemiology
Issue number8
Publication statusPublished - Dec 2009
Externally publishedYes
Event18th Annual Meeting of the International-Genetic-Epidemiology-Society - Honolulu
Duration: 10 Oct 200920 Oct 2009


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