Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Observational Study
. 2018 Jul;138(7):1620-1626.
doi: 10.1016/j.jid.2018.01.021. Epub 2018 Feb 8.

Risks of Melanoma and Other Cancers in Melanoma-Prone Families over 4 Decades

Margaret A Tucker  1 , David E Elder  2 , Michael Curry  3 , Mary C Fraser  4 , Virginia Pichler  5 , Deborah Zametkin  5 , Xiaohong R Yang  4 , Alisa M Goldstein  4
Affiliations
Observational Study

Risks of Melanoma and Other Cancers in Melanoma-Prone Families over 4 Decades

Margaret A Tucker et al. J Invest Dermatol. 2018 Jul.

Abstract

Since 1976, melanoma-prone families have been followed at the National Cancer Institute to identify etiologic factors for melanoma. We compared risks of melanoma and other cancers in 1,226 members of 56 families followed for up to 4 decades with population rates in the Surveillance, Epidemiology, and End Results program. All families were tested for mutations in CDKN2A and CDK4; 29 were mutation-positive and 27 mutation-negative. We compared rates of invasive melanomas, both first and second, by family mutation status, with Surveillance, Epidemiology, and End Results program. Comparing three calendar periods of the study, risk of first primary melanoma decreased slightly. Risks of melanoma after first examination, however, were approximately one-third the risks prior to the first examination in both mutation-positive and mutation-negative families. Among patients with melanoma, risk of a second melanoma was increased 10-fold in all families; risk was somewhat higher in mutation-positive families. Risks of other second cancers were increased only for pancreatic cancer after melanoma in mutation-positive families. Over 4 decades, prospective risk of melanoma has decreased substantially in both mutation-positive and mutation-negative families, when melanoma has greatly increased in the general population.

Trial registration: NCI 02-C-0211, ClinicalTrials.gov ID NCT00040352.

PubMed Disclaimer

Conflict of interest statement

Conflict of Interest

The authors state no conflicts of interest.

Figures

Figure 1.
Figure 1.
Invasive, multiple primary, and in situ melanomas in all cases. Total number of melanomas in probands (n = 136, left), retrospective cases (n = 97, middle), and prospective cases (n = 30, right). Each circle shows the distribution of invasive single primary, invasive multiple primary, and in situ melanomas for each case group, comprising all melanomas with tumor data available, including cases not clinically examined. Most cases were either probands (defining their families as eligible for study) or retrospective cases (individuals with first melanoma prior to study participation). There were many fewer prospective cases, individuals who developed their first melanoma after first study examination. The distribution of invasive single primary, invasive multiple primary, and in situ melanomas across the three case groups was significantly different (P < 0.0001).
Figure 2.
Figure 2.
Age, gender, and calendar-period specific melanoma incidence in Seer9 (1975–2013), mutation-positive families, and mutation-negative families. The numbers under the x-axis reflect the number of individuals in mutation-negative families in red and mutation-positive families in blue. The orange dashed line represents the age-specific first primary melanoma incidence in SEER; the red solid line represents the age-specific risk of first melanoma in the mutation-negative families; and the blue dashed line represents the age-specific incidence in mutation-positive families; overall log-rank P < 0.0001. The log-rank P value for the comparison of the families is 0.0112. The blue and red shading represent the 95% Hall-Wellner bands for the familial data. Seer, Surveillance, Epidemiology, and End Results program.
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

References

    1. Bishop et al., 2002 Bishop DT, Demenais F, Goldstein AM, Bergman W, Bishop JN, Bressac-de Paillerets B, et al. Geographical variation in the penetrance of CDKN2A mutations for melanoma J Natl Cancer Inst, 94 (2002), pp. 894–903 - PubMed
    1. Curtis et al., 2005 Curtis RE, Freedman DM, Ron E, Ries LAG, Hacker DG, Edwards BK, et al. editors. New Malignancies Among Cancer Survivors: SEER Cancer Registries, 1973– 2000. NIH Publ. No. 05–5302. National Cancer Institute Bethesda, MD; 2005.
    1. Cust et al., 2011 Cust A, Harland M, Makalic E, Schmidt D, Dowty JG, Aitken JF, et al. Melanoma risk for CDKN2A mutation carriers who are relatives of population-based case carriers in Australia and the UK J Med Genet, 48 (2011), pp. 266–272 - PMC - PubMed
    1. Demenais et al., 2010 Demenais F, Mohamdi H, Chaudru V, Goldstein A, Newton JA Bishop DT Bishop, et al. Association of MCIR variants and host phenotypes with melanoma risk in CDKN2A mutation carriers: a GenoMEL study J Natl Cancer Inst, 102 (2010), pp. 1568–1583 - PMC - PubMed
    1. de Snoo et al., 2008 de Snoo FA, Bishop DT, Bergman W, van Leeuwen, van der Drift C, van Nieuwpoort FA, et al. Increased risk of cancer other than melanoma in CDKN2A founder mutation (P16- Leiden) positive families Clin Cancer Res, 14 (2008), pp. 7151–7157 - PubMed

Publication types

MeSH terms

Substances

Associated data