Among US participants familiar with their hereditary melanoma risk through prior epidemiological research participation, CDKN2A/p16 genetic testing provides multiple perceived benefits to both carriers and noncarriers without inducing distress in general or worry about melanoma or pancreatic cancer.
Although early age at melanoma diagnosis and occurrence of multiple primary melanoma in 1 or more patient were significantly associated with the risk of a CDKN2A mutation in F2 families, early age at melanoma diagnosis and occurrence of pancreatic cancer in a family were significantly associated with CDKN2A mutations in F3+ families.
Genetic mutations, such as activation of the KRAS2 oncogene, inactivation of the tumor-suppressor gene CDKN2A, inactivation of the tumor-suppressor gene TP53 and deleted in pancreatic cancer 4 (DPC4) gene defects are seen in those with pancreatic cancer.
CDKN2A mutation carriers were more likely to have a family history of pancreatic cancer (P=0.003) or melanoma (P=0.03), and a personal history of melanoma (P=0.01).
To verify the S305N association with melanoma risk in an independent larger French population (378 patients, 389 controls); to investigate the role of EDNRB variants in melanoma risk in an Italian population (133 patients, 118 controls); and to explore the association of CDKN2A or CDK4 mutations with the S305N EDNRB variant in a subgroup of patients (59 French, 12 Italian) with a suspected hereditary predisposition to melanoma (familial melanoma, sporadic multiple primary melanoma or melanoma associated with pancreatic cancer).
In addition, no significant associations were observed between 11 PALB2 tagging SNPs and melanoma risk in 23 melanoma-prone families with CDKN2A mutations or the subset of 11 families with PC or PC-related CDKN2A mutations.
Some CDKN2A mutations have been associated not only with melanoma but also with increased risk of other malignancies--most notably pancreatic carcinoma.
Previous small scale studies reported that deleterious BRCA2 and CDKN2a germline mutations contribute to a subset of families with inherited pancreatic cancer.
Pancreatic cancer is associated with mutations in the tumor suppressor gene cyclin-dependent kinase inhibitor 2A (p16(INK4A) ), a regulator of the cell cycle and apoptosis.
Except in regions of high melanoma incidence, such as Australia, we found higher rates of CDKN2A positivity in individuals with 3 or more primary invasive melanomas and/or families with at least one invasive melanoma and two or more other diagnoses of invasive melanoma and/or pancreatic cancer among first- or second-degree relatives on the same side of the family.
We conclude that HNSCC in young individuals should prompt clinicians to obtain a family history and consider that the patient may have a germline p16 defect that could predispose them to other cancers, including melanoma and pancreatic cancer.
In a Dutch family with atypical phenotypic presentation of the familial atypical multiple mole melanoma syndrome with high incidence of PC related to a mutation in the CDKN2A gene, pancreatic surveillance was offered to asymptomatic gene mutation carriers.
Here, we inducibly re-expressed p16 in vivo in an orthotopic model of pancreatic cancer and examined the impact on these clinically relevant aspects of pancreatic cancer tumour biology.
We also present evidence indicating that, when performed serially in individuals harboring a p16 germ-line mutation bestowing a high risk for pancreatic cancer, MLDA may be an effective tool for the longitudinal assessment of risk and early detection of pancreatic cancer.
Alterations in the ARF tumor suppressor protein (also known as p14ARF in humans and p19ARF in the mouse) occur frequently in cancer and are associated with susceptibility to melanoma, pancreatic cancer and nervous system tumors.
Tumor suppressor p16INK4a--modulator of glycomic profile and galectin-1 expression to increase susceptibility to carbohydrate-dependent induction of anoikis in pancreatic carcinoma cells.
Individuals with a high-risk genetic background require counseling, genetic testing if appropriate (BRCA2 mutation or p16INK4A inactivity) and secondary screening for pancreatic cancer in specialist centers.
All four features in each group, except pancreatic cancer in Australia (p = 0.38), individually showed significant associations with CDKN2A mutations, but the effects varied widely across continents.