Increased Prevalence of Lung, Breast, and Pancreatic Cancers in Addition to Melanoma Risk in Families Bearing the Cyclin-Dependent Kinase Inhibitor 2A Mutation: Implications for Genetic Counseling

J Am Acad Dermatol. 2014 Nov;71(5):888-95. doi: 10.1016/j.jaad.2014.06.036. Epub 2014 Jul 24.

Abstract

Background: Cyclin-dependent kinase inhibitor 2A (CDKN2A) is the major high-risk susceptibility gene for melanoma.

Objective: We sought to evaluate the effect of CDKN2A mutations in Spanish patients with a high risk of developing melanoma and the association with clinical and family history features.

Methods: A cross-sectional study design was used to analyze the CDKN2A impact in 702 Spanish patients with a high risk of developing melanoma.

Results: The CDKN2A mutation prevalence was 8.5% in patients with sporadic multiple primary melanoma and 14.1% in familial melanoma. Number of cases in the family, number of primary melanomas, and age of onset were associated with the presence of CDKN2A mutation. Having a CDKN2A mutation in the family increased the prevalence of other cancers (prevalence ratio [PR] 2.99, P=.012) and prevalence of pancreatic (PR 2.97, P=.006), lung (PR 3.04, P<.001), and breast (PR 2.19, P=.018) cancers but not nephrourologic or colon cancer.

Limitations: Smoking status was not assessed in the individuals with lung cancer.

Conclusions: Melanoma-prone families with mutations in CDKN2A have an increased prevalence of a broad spectrum of cancers including lung, pancreatic, and breast cancer. This information should be included in genetic counseling and cancer prevention programs for CDKN2A mutation carriers.

Keywords: CDKN2A; breast cancer; genetic counseling; lung cancer; melanoma; pancreatic cancer; prevention; risk; smoking.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Age of Onset
  • Aged
  • Breast Neoplasms / epidemiology*
  • Breast Neoplasms / genetics
  • Cross-Sectional Studies
  • Cyclin-Dependent Kinase Inhibitor p16 / genetics*
  • Genetic Counseling
  • Genetic Predisposition to Disease / epidemiology
  • Genetic Predisposition to Disease / genetics
  • Humans
  • Lung Neoplasms / epidemiology*
  • Lung Neoplasms / genetics
  • Melanoma / epidemiology*
  • Melanoma / genetics
  • Middle Aged
  • Pancreatic Neoplasms / epidemiology*
  • Pancreatic Neoplasms / genetics
  • Prevalence
  • Risk Factors
  • Skin Neoplasms / epidemiology*
  • Skin Neoplasms / genetics
  • Spain / epidemiology

Substances

  • Cyclin-Dependent Kinase Inhibitor p16