title: MC1R common variants, CDKN2A and their association with melanoma and breast cancer risk.
abstract: We sought to examine the association between MC1R variants and the risk of melanoma and breast cancer in Polish population. We also determined the prevalence of compound heterozygous carriers of MC1R and CDKN2A (A148T) variants. We examined 500 unselected melanoma cases, 511 consecutive invasive breast cancer patients, 800 newborns, 421 healthy adults matched for sex and age with the melanoma cases and 511 healthy women matched for sex and age with the breast cancer cases. A statistically significant association of all 4 MC1R variants with the melanoma risk was found. For the R151C variant p value was 0.000008 and odds ratio 2.9; for the V60L variant p value was 0.007 and OR 1.78; for the R160C p was 0.006 and OR 1.76; for the R163Q p was 0.015 and odds ratio 2.1. None of the compound heterozygotes were significantly over-represented among any of the melanoma cases, the highest OR (4.2) observed in patients harbouring the A148T variant in CDKN2A and the R151C variant in MC1R. Positive association was found between carrying any of the MC1R variants and (i) increased occurrence of melanoma among I degree relatives of the carriers; (ii) increased occurrence of melanoma on UV-non-exposed skin areas. We also observed a tendency of increased risk of multiple melanomas among carriers of MC1R variants. The haplotype analysis demonstrates that MC1R variants do not co-occur in cis, compound carriers have both alleles affected. We found no association with the MC1R variants and breast cancer risk. In conclusion, the results of this population-based study show herein that MC1R variants are associated with increased melanoma risk in the Polish population. The risk of disease seems to be increased additively for patients harbouring also the CDKN2A common variant A148T.
authors.affiliation: Department of Genetics and Pathology, International Hereditary Cancer Centre, Pomeranian Medical University, Szczecin, Poland. debniak@wp.pl
authors.forename: Tadeusz
authors.initials: T
authors.lastname: Debniak
authors.forename: Rodney
authors.initials: R
authors.lastname: Scott
authors.forename: Bartłomiej
authors.initials: B
authors.lastname: Masojc
authors.forename: Pablo
authors.initials: P
authors.lastname: Serrano-Fernández
authors.forename: Tomasz
authors.initials: T
authors.lastname: Huzarski
authors.forename: Tomasz
authors.initials: T
authors.lastname: Byrski
authors.forename: Bogusław
authors.initials: B
authors.lastname: Debniak
authors.forename: Bohdan
authors.initials: B
authors.lastname: Górski
authors.forename: Cezary
authors.initials: C
authors.lastname: Cybulski
authors.forename: Krzysztof
authors.initials: K
authors.lastname: Medrek
authors.forename: Grzegorz
authors.initials: G
authors.lastname: Kurzawski
authors.forename: Thierry
authors.initials: T
authors.lastname: van de Wetering
authors.forename: Romuald
authors.initials: R
authors.lastname: Maleszka
authors.forename: Józef
authors.initials: J
authors.lastname: Kładny
authors.forename: Jan
authors.initials: J
authors.lastname: Lubinski
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001483:Base Sequence; D001943:Breast Neoplasms / Q000235:genetics*; D016022:Case-Control Studies; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000235:genetics*; D017931:DNA Primers; D005260:Female; D006239:Haplotypes; D006801:Humans; D015810:Linkage Disequilibrium; D008297:Male; D008545:Melanoma / Q000235:genetics*; D008875:Middle Aged; D044102:Receptor, Melanocortin, Type 1 / Q000235:genetics*
chemical_list: D019941:Cyclin-Dependent Kinase Inhibitor p16; D017931:DNA Primers; D044102:Receptor, Melanocortin, Type 1