Matrix Metalloproteinase-9 (MMP-9) polymorphisms in patients with cutaneous malignant melanoma.
Matrix Metalloproteinase-9 (MMP-9) polymorphisms in patients with cutaneous malignant melanoma.
复制标题
皮肤恶性黑色素瘤患者的基质金属蛋白酶9（MMP-9）多态性。
DOI：
10.1186/1471-2350-8-10
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发表时间：
2007-03-08
影响因子：
--
通讯作者：
Orlow, Irene
中科院分区：
文献类型：
--
作者：
Cotignola, Javier;Reva, Boris;Mitra, Nandita;Ishill, Nicole;Chuai, Shaokun;Patel, Ami;Shah, Shivang;Vanderbeek, Gretchen;Coit, Daniel;Busam, Klaus;Halpern, Allan;Houghton, Alan;Sander, Chris;Berwick, Marianne;Orlow, Irene
皮肤恶性黑色素瘤导致超过75%的皮肤癌相关死亡，很明显，许多因素可能导致结果。基质金属蛋白酶（MMPs）在细胞外基质和基底膜的降解和重塑中起重要作用，其反过来调节细胞分裂、迁移和血管生成。已知一些多态性影响基因表达、蛋白质活性、稳定性和相互作用，并且它们被证明与某些肿瘤表型和癌症风险相关。我们在1002例黑色素瘤患者中检测了MMP-9基因的7种多态性，以评估生殖系遗传变异及其与黑色素瘤进展和已知危险因素的相关性。使用计算机模拟方法，基于先前发表的报告及其已知或潜在的功能相关性选择多态性。然后使用焦磷酸测序、解链温度曲线、异源双链分析和片段大小分析对种系DNA进行基因分型。我们发现，参考等位基因在倾向于晒伤、有黑色素瘤家族史、黑色素瘤分期较高、转移和促结缔组织增生性黑色素瘤等患者中的频率较高。然而，在调整了年龄、性别、表型指数、痣和雀斑后，只有Q279 R、P574 R和R668 Q与转移、晒黑/晒伤倾向和原发性黑色素瘤部位显著相关。这项研究没有提供有力的证据，进一步调查MMP-9 SNP在黑色素瘤进展中的作用。
Cutaneous Malignant Melanoma causes over 75% of skin cancer-related deaths, and it is clear that many factors may contribute to the outcome. Matrix Metalloproteinases (MMPs) play an important role in the degradation and remodeling of the extracellular matrix and basement membrane that, in turn, modulate cell division, migration and angiogenesis. Some polymorphisms are known to influence gene expression, protein activity, stability, and interactions, and they were shown to be associated with certain tumor phenotypes and cancer risk. We tested seven polymorphisms within the MMP-9 gene in 1002 patients with melanoma in order to evaluate germline genetic variants and their association with progression and known risk factors of melanoma. The polymorphisms were selected based on previously published reports and their known or potential functional relevance using in-silico methods. Germline DNA was then genotyped using pyrosequencing, melting temperature profiles, heteroduplex analysis, and fragment size analysis. We found that reference alleles were present in higher frequency in patients who tend to sunburn, have family history of melanoma, higher melanoma stage, intransit metastasis and desmoplastic melanomas among others. However, after adjustment for age, sex, phenotypic index, moles, and freckles only Q279R, P574R and R668Q had significant associations with intransit metastasis, propensity to tan/sunburn and primary melanoma site. This study does not provide strong evidence for further investigation into the role of the MMP-9 SNPs in melanoma progression.
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DOI：
10.1016/s0006-291x(02)02283-0
发表时间：
2002-10-04
影响因子：
3.1
作者：
Chicoine, É;Estève, PO;St-Pierre, Y
通讯作者：
St-Pierre, Y
影响因子：
6.5
作者：
Hofmann, UB;Westphal, JR;Ruiter, DJ
通讯作者：
Ruiter, DJ
影响因子：
4.1
作者：
Orlow, I;Roy, P;Berwick, M
通讯作者：
Berwick, M
影响因子：
4
作者：
Ferrand, PE;Parry, S;Strauss, JF
通讯作者：
Strauss, JF
影响因子：
1.9
作者：
Sasieni, PD
通讯作者：
Sasieni, PD