CDKN2A mutation status, family history of melanoma tied to worse outcomes in MPM patients
Family history of melanoma and CDKN2A mutation status significantly affect the risks of developing subsequent melanomas and other cancers and survival outcomes in patients with multiple primary melanomas (MPMs), a recent study has shown.
To determine how family history of melanoma and germline CDKN2A mutation status affected outcomes of MPM patients, researchers retrieved comprehensive data on cancer diagnoses and deaths of MPM patients, their first-degree relatives and matched controls from Swedish national healthcare and population registries.
Familial cases of MPM with germline CDKN2A mutations were youngest at the diagnosis of their second melanoma (median age 42 years) and had the highest relative risks (RR) of developing >2 melanomas (RR, 238.4; 95 percent CI, 74.8 to 759.9) among the MPM cohorts compared with controls.
Compared to controls, only those with CDKN2A-mutated MPM cases (RR, 3.6; 1.9 to 147.1) and their first-degree relatives (RR, 3.2; 1.9 to 5.6) had elevated risks of nonskin cancers. Moreover, survival was worse in CDKN2A-mutated MPM cases compared with both cases with familial (hazard ratio [HR], 3.0; 1.3 to 8.1) and sporadic wild-type MPM (HR, 2.63; 1.3 to 5.4).
“Our study examined outcomes in subgroups of MPM patients, which affected the sample size of the study groups,” researchers noted.
In a separate study, the same researchers concluded that CDKN2A-mutated cases had significantly worse survival than nonskin cancers and from melanoma compared with melanoma cases without CDKN2A mutations. [J Natl Cancer Inst 2016;doi:10.1093/jnci/djw135]
“Further studies are required to elucidate possible mechanisms behind increased carcinogen susceptibility and the more aggressive melanoma phenotype in CDKN2A mutation carriers,” they added.