Missense polymorphisms in matrix metalloproteinase genes and skin cancer risk.
Matrix metalloproteinases (MMP) degrade various components of the extracellular matrix, and their overexpression has been implicated in tumor progression. Nonsynonymous single nucleotide polymorphisms (SNPs) lead to amino acid substitutions that can alter the function of the encoded protein. We evaluated the associations of six nonsynonymous SNPs in the MMP3, MMP8, and MMP9 genes with skin cancer risk in a nested case-control study of Caucasians within the Nurses' Health Study among 218 melanoma cases, 285 squamous cell carcinoma (SCC) cases, 300 basal cell carcinoma (BCC) cases, and 870 normal controls. We observed that the MMP9 Arg668Gln polymorphism was significantly associated with a decreased risk of SCC. Compared with the Arg/Arg group, the multivariate odds ratio was 0.67 (95% confidence interval, 0.47-0.97) for the Arg/Gln group and 0.21 (95% confidence interval, 0.05-0.97) for the Gln/Gln group (P(trend) = 0.004). We did not observe any association of this SNP with the risks of melanoma and basal cell carcinoma. No associations were found for other SNPs with skin cancer risk. This study provides evidence for the contribution of the MMP9 Arg668Gln to SCC development.
Nan
Hongmei
H
Program in Molecular and Genetic Epidemiology, Department of Epidemiology, Harvard School of Public Health, 677 Huntington Avenue, Boston, MA 02115, USA. hnan@hsph.harvard.edu
Niu
Tianhua
T
Hunter
David J
DJ
Han
Jiali
J
D000328:Adult; D002280:Basal Cell Carcinoma / Q000235:genetics; D002294:Carcinoma, Squamous Cell / Q000235:genetics; D016022:Case-Control Studies; D016009:Chi-Square Distribution; D005260:Female; D005838:Genotype; D006239:Haplotypes; D006801:Humans; D016015:Logistic Models; D020782:Matrix Metalloproteinases / Q000235:genetics*; D008545:Melanoma / Q000235:genetics; D008875:Middle Aged; D020125:Mutation, Missense; D011110:Polymorphism, Genetic; D020641:Polymorphism, Single Nucleotide; D012306:Risk; D012878:Skin Neoplasms / Q000235:genetics*; D014481:United States; D044465:White People / Q000235:genetics
D020782:Matrix Metalloproteinases