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

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.