Missense polymorphisms in matrix metalloproteinase genes and skin cancer risk.
Missense polymorphisms in matrix metalloproteinase genes and skin cancer risk.
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DOI：
10.1158/1055-9965.epi-08-0606
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发表时间：
2008-12
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影响因子：
--
通讯作者：
Han J
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文献类型：
--
作者：
Nan H;Niu T;Hunter DJ;Han J
基质金属蛋白酶（MMP）降解细胞外基质（ECM）的各种成分，它们的过度表达与肿瘤进展有关。非同义 SNP 会导致氨基酸取代，从而改变所编码蛋白质的功能。我们在护士健康研究 (NHS) 的白种人巢式病例对照研究中评估了 MMP3、MMP8 和 MMP9 基因中的 6 个非同义 SNP 与皮肤癌风险的关联，其中包括 218 例黑色素瘤病例、285 例鳞状细胞癌 (SCC) 病例、300 例基底细胞癌 (BCC) 病例和 870 例正常对照。我们观察到 MMP9 Arg668Gln 多态性与鳞状细胞癌风险降低显着相关。与Arg/Arg组相比，Arg/Gln组的多变量比值比（OR）为0.67（95%置信区间（95% CI），0.47-0.97），Gln/Gln组为0.21（95% CI，0.05-0.97）（趋势P，0.004）。我们没有观察到该 SNP 与黑色素瘤和基底细胞癌风险有任何关联。没有发现其他 SNP 与皮肤癌风险之间的关联。这项研究为 MMP9 Arg668Gln 对 SCC 发展的贡献提供了证据。
Matrix metalloproteinases (MMPs) degrade various components of the extracellular matrix (ECM), and their overexpression has been implicated in tumor progression. Non-synonymous SNPs lead to amino acid substitutions that can alter the function of the encoded protein. We evaluated the associations of six non-synonymous 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 (NHS) 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 (OR) was 0.67 (95% confidence interval (95% CI), 0.47-0.97) for the Arg/Gln group and 0.21 (95% CI, 0.05-0.97) for the Gln/Gln group (P for trend, 0.004). We did not observe any association of this SNP with the risks of melanoma and BCC. 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.