title: Characterization of ligurian melanoma families and risk of occurrence of other neoplasia.
abstract: Germline mutations impairing the p16(INK4)-function have previously been demonstrated to be responsible for genetic predisposition in at least one half of melanoma-prone kindreds of North European origin. Familial melanoma kindreds have also been found to present an increased risk of pancreatic cancer and other cancers, but results relative to more common neoplasias incidence, in particular, are heterogeneous. We report here a clinical-epidemiological study, including the presence of additional neoplasias, in 14 apparently unrelated kindreds coming from a small geographic region of Northern Italy (Liguria), having therefore lived for generations in similar environmental conditions. We identified the common p16 missense mutation (Gly101Trp) reported in several previously studied kindreds, in 7 of 14 families, whereas the remaining 7 families had no detectable mutations in the coding region of p16 gene. Median age at diagnosis and other melanoma features were studied. When compared with the expected figures, based on regional incidence rates, a significant excess of pancreatic cancer, with 4 cases diagnosed, and of breast cancer, with 7 cases, was observed. The 7 families without apparent CDKN2A involvement were also negative for hot-spot exon 2 mutation of CDK4. Environmental factors do not appear to play a role in the excess of non-melanoma neoplasia in our families, as somewhat substantiated by the control group, composed of spouses and members of non-affected branches; they do not reveal any increased cancer incidence compared with the general population. Furthermore, given the proven significance of interaction between the melanoma susceptibility gene and the propensity to sunburns and other environmental risk factors, our results, obtained from a small but homogeneous sample, may have important implications for further risk assessment studies.
authors.affiliation: Dipartimento di Oncologia, Biologia e Genetica, Università degli Studi di Genova, Genova, Italy.
authors.forename: P
authors.initials: P
authors.lastname: Ghiorzo
authors.forename: P
authors.initials: P
authors.lastname: Ciotti
authors.forename: M
authors.initials: M
authors.lastname: Mantelli
authors.forename: A
authors.initials: A
authors.lastname: Heouaine
authors.forename: P
authors.initials: P
authors.lastname: Queirolo
authors.forename: M L
authors.initials: ML
authors.lastname: Rainero
authors.forename: C
authors.initials: C
authors.lastname: Ferrari
authors.forename: P L
authors.initials: PL
authors.lastname: Santi
authors.forename: R
authors.initials: R
authors.lastname: De Marchi
authors.forename: A
authors.initials: A
authors.lastname: Farris
authors.forename: F
authors.initials: F
authors.lastname: Ajmar
authors.forename: P
authors.initials: P
authors.lastname: Bruzzi
authors.forename: G
authors.initials: G
authors.lastname: Bianchi-Scarrà
mesh_terms: D000293:Adolescent; D000328:Adult; D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D001943:Breast Neoplasms / Q000453:epidemiology / Q000235:genetics*; D002648:Child; D004252:DNA Mutational Analysis; D004781:Environmental Exposure; D005260:Female; D019942:Genes, p16; D006801:Humans; D015994:Incidence; D007558:Italy / Q000453:epidemiology; D008297:Male; D008545:Melanoma / Q000453:epidemiology / Q000235:genetics*; D008875:Middle Aged; D016609:Neoplasms, Second Primary / Q000453:epidemiology / Q000235:genetics; D010190:Pancreatic Neoplasms / Q000453:epidemiology / Q000235:genetics*; D010375:Pedigree; D018570:Risk Assessment; D012737:Sex Factors; D012878:Skin Neoplasms / Q000453:epidemiology / Q000235:genetics*