MC1R variation and melanoma risk in relation to host/clinical and environmental factors in  CDKN2A positive and negative melanoma patients.
Host, environmental and genetic factors differently modulate cutaneous melanoma (CM) risk across populations. Currently, the main genetic risk determinants are germline mutations in the major known high-risk susceptibility genes, CDKN2A and CDK4, and variants of the low-risk gene MC1R, which is key in the pigmentation process. This case-control study aimed at investigating the influence of the main host and environmental risk factors and of MC1R variation on CM risk in 390 CDKN2A-negative and 49 CDKN2A-positive Italian individuals. Multivariate analysis showed that MC1R variation, number of nevi and childhood sunburns doubled CM risk in CDKN2A-negative individuals. In CDKN2A-positive individuals, family history of CM and presence of atypical nevi, rather than MC1R status, modified risk (20.75- and 2.83-fold, respectively). Occupational sun exposure increased CM risk (three to sixfold) in both CDKN2A-negative and CDKN2A-positive individuals, reflecting the occupational habits of the Ligurian population and the geographical position of Liguria.
Department of Internal Medicine and Medical Specialties, University of Genoa, Genoa, Italy. paola.ghiorzo@unige.it
Paola
P
Ghiorzo
Luigina
L
Bonelli
Lorenza
L
Pastorino
William
W
Bruno
Monica
M
Barile
Virginia
V
Andreotti
Sabina
S
Nasti
Linda
L
Battistuzzi
Marco
M
Grosso
Giovanna
G
Bianchi-Scarrà
Paola
P
Queirolo
D000293:Adolescent; D000328:Adult; D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D016022:Case-Control Studies; D016001:Confidence Intervals; D005260:Female; D019942:Genes, p16; D006801:Humans; D007558:Italy; D008297:Male; D008545:Melanoma / Q000209:etiology / Q000235:genetics*; D008875:Middle Aged; D015999:Multivariate Analysis; D009154:Mutation; D009506:Nevus / Q000473:pathology; D016273:Occupational Exposure / Q000009:adverse effects*; D016017:Odds Ratio; D044102:Receptor, Melanocortin, Type 1 / Q000235:genetics*; D012307:Risk Factors; D012878:Skin Neoplasms / Q000209:etiology / Q000235:genetics*; D013471:Sunburn / Q000150:complications; D013472:Sunlight / Q000009:adverse effects*; D055815:Young Adult
D044102:Receptor, Melanocortin, Type 1