title: Association of MMP8 gene variation with an increased risk of malignant melanoma.
abstract: Matrix metalloproteinases (MMPs) are implicated in the development of cancers including malignant melanoma (MM) and breast cancer. We tested the possible association of MMP1 and MMP8 gene variation with these two types of cancer. We genotyped 300 unselected patients with MM, 300 consecutive breast cancer cases, 300 controls for melanoma, and 300 controls for breast cancer (age-matched and sex-matched healthy adults with negative cancer family histories). Our study showed that the MMP8 gene rs11225395 polymorphism was associated with the risk of developing MM (odds ratio: 1.69; 95% confidence interval: 1.02-2.80; P=0.040) for the A/A genotype and 1.49 (95% confidence interval: 1.03-2.17; P=0.035) for the A/G genotype compared with the G/G genotype. The A allele was over-represented among MM cases compared with controls (odds ratio=1.54; P=0.017). In-vitro assays showed that the A allele had a higher promoter activity than the G allele in melanoma cells. No association was detected between this variant and breast cancer susceptibility. We found no strong association between MMP1 variation and the risk of MM or breast cancer. The finding of this study indicates an influence of MMP8 gene variation on melanoma susceptibility.
authors.affiliation: Department of Genetics and Pathology, International Hereditary Cancer Centre, Pomeranian Medical University, Szczecin, Poland. debniak@ams.edu.pland
authors.forename: Tadeusz
authors.initials: T
authors.lastname: Dębniak
authors.forename: Anna
authors.initials: A
authors.lastname: Jakubowska
authors.forename: Pablo
authors.initials: P
authors.lastname: Serrano-Fernández
authors.forename: Grzegorz
authors.initials: G
authors.lastname: Kurzawski
authors.forename: Cezary
authors.initials: C
authors.lastname: Cybulski
authors.forename: Saleena Rani
authors.initials: SR
authors.lastname: Chauhan
authors.forename: Ross C
authors.initials: RC
authors.lastname: Laxton
authors.forename: Romuald
authors.initials: R
authors.lastname: Maleszka
authors.forename: Jan
authors.initials: J
authors.lastname: Lubinski
authors.forename: Shu
authors.initials: S
authors.lastname: Ye
mesh_terms: D016022:Case-Control Studies; D005260:Female; D020022:Genetic Predisposition to Disease; D014644:Genetic Variation; D005838:Genotype; D006801:Humans; D008297:Male; D020784:Matrix Metalloproteinase 8 / Q000235:genetics*; D008545:Melanoma / Q000201:enzymology / Q000235:genetics*; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D012307:Risk Factors; D012878:Skin Neoplasms / Q000201:enzymology / Q000235:genetics*
chemical_list: D020784:Matrix Metalloproteinase 8