Compared with baseline, CDKN2A/p16+ participants without a melanoma history reported greater intention to obtain total body skin examinations (P < 0.0001), increased intentions and adherence to skin self-examination recommendations (P < 0.01 and P < 0.001, respectively), and increased number of body sites examined at 1 month (P < 0.002); further, 55% reported adopting a new screening behavior at follow-up.
The results of this study revealed a paucity of mutations in CDKN2A/ARF suggesting that in the Polish population this gene does not contribute significantly to early-onset breast cancer, pancreatic cancer and malignant melanoma.
This population based study of Icelandic melanoma cases and controls showed a frequency of disease related CDKN2A mutant alleles ranging from 0.7% to 1.0%, thus expanding our knowledge about the frequency of CDKN2A mutations in different populations.
Compared to SPM patients, the risk of harboring a CDKN2A mutation rose as the number of primary melanomas increased and was not influenced by family history.
Genetic and epigenetic analyses of the human 9p21 locus indicate that modifications of ARF occur independently of p16 inactivation in human melanoma and suggest that ARF is more frequently inactivated than p16.
In Europe and North America, between 8-14% of melanoma patients have a family history of the disease, and a subset of these individuals possess germline mutations in the CDKN2A gene, which encodes the p16(INK4A) and p14(ARF) tumor suppressors.
Germline mutations of the CDKN2A gene are found in < 25% of melanoma-prone families and there are only seven families with mutation of the CDK4 gene reported to date.
We identified five novel CDKN2A variants (Ala57Gly, Pro81Arg, Ala118Val, Leu130Val, and Arg131Pro) and four that previously have been reported in melanoma families (Glu27X, Met53Ile, Arg87Trp, and Ala127Pro).
The relatively low rate of CDKN2A mutation detection is not due to failure to detect mutations and implies the existence of other high penetrance melanoma susceptibility genes.
Furthermore, we observed that a carrier of the founder CDKN2A [p.Leu113Leu;p.Pro114Ser] mutation as well as two MC1R moderate-risk variants, [p.Arg151Cys(+)p.Arg163Gln] developed 22 primary melanomas in the three years that followed initiation of levodopa therapy for Parkinson's disease.
The obtained results allow us to conclude: (i) survival times of 500 C/G carriers vs. cumulating proportion surviving was not statistically significant; (ii) CDKN2a polymorphism 500 C/G correlated with Ala148Thr; (iii) no correlation was observed between the 500 C/G polymorphism and age of diagnosis, localization of primary melanoma and survival time; (iv) we did not find correlation between 500 C/G and type of cancer in the family; (v) changes in the CDKN2a gene were not found in patients with second cancer.
No disease-related CDKN2A germline mutations were identified in any of the melanoma patients analysed but the previously described CDK4 mutation, Arg24His, was found in one patient with a family history of melanoma.
The M53I mutation is the most common CDKN2A mutation identified in Scottish melanoma patients and is also found in a small number of families in other countries.
The variation in CDKN2A mutations for the four features across continents is consistent with the lower melanoma incidence rates in Europe and higher rates of sporadic melanoma in Australia.