title: Association between HRAS rs12628 and rs112587690 polymorphisms with the risk of melanoma in the North American population.
abstract: HRAS belongs to the RAS genes superfamily. RAS genes are important players in several human tumors and the single-nucleotide polymorphism rs12628 has been shown to contribute to the risk of bladder, colon, gastrointestinal, oral, and thyroid carcinoma. We hypothesized that this SNP may affect the risk of cutaneous melanoma as well. HRAS gene contains a polymorphic region (rs112587690), a repeated hexanucleotide -GGGCCT- located in intron 1. Three alleles of this region, P1, P2, and P3, have been identified that contain two, three, and four repeats of the hexanucleotide, respectively. We investigated the clinical impact of these polymorphisms in a case-control study. A total of 141 melanoma patients and 118 healthy donors from the North America Caucasian population were screened for rs12628 and rs112587690 polymorphisms. Genotypes were assessed by capillary sequencing or fragment analysis, respectively, and rs12628 CC and rs112587690 P1P1 genotypes significantly associated with increased melanoma risk (OR = 3.83, p = 0.003; OR = 11.3, p = 0.033, respectively), while rs112587690 P1P3 frequency resulted significantly higher in the control group (OR = 0.5, p = 0.017). These results suggest that rs12628 C homozygosis may be considered a potential risk factor for melanoma development in the North American population possibly through the linkage to rs112587690.
authors.affiliation: Division of Surgical, Molecular, and Ultrastructural Pathology, Section of Molecular Pathology, University of Pisa and Pisa University Hospital, 56100, Pisa, Italy. tomeis@mail.nih.gov
authors.forename: Sara
authors.initials: S
authors.lastname: Tomei
authors.forename: Sharon
authors.initials: S
authors.lastname: Adams
authors.forename: Lorenzo
authors.initials: L
authors.lastname: Uccellini
authors.forename: Davide
authors.initials: D
authors.lastname: Bedognetti
authors.forename: Valeria
authors.initials: V
authors.lastname: De Giorgi
authors.forename: Narnygerel
authors.initials: N
authors.lastname: Erdenebileg
authors.forename: Maria Libera
authors.initials: ML
authors.lastname: Ascierto
authors.forename: Jennifer
authors.initials: J
authors.lastname: Reinboth
authors.forename: Qiuzhen
authors.initials: Q
authors.lastname: Liu
authors.forename: Generoso
authors.initials: G
authors.lastname: Bevilacqua
authors.forename: Ena
authors.initials: E
authors.lastname: Wang
authors.forename: Chiara
authors.initials: C
authors.lastname: Mazzanti
authors.forename: Francesco M
authors.initials: FM
authors.lastname: Marincola
mesh_terms: D020022:Genetic Predisposition to Disease / Q000235:genetics*; D005838:Genotype; D006801:Humans; D008545:Melanoma / Q000235:genetics*; D009656:North America; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D016283:Proto-Oncogene Proteins p21(ras) / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012307:Risk Factors; D012878:Skin Neoplasms / Q000235:genetics*; D044465:White People
chemical_list: C501009:HRAS protein, human; D016283:Proto-Oncogene Proteins p21(ras)