Pigmentation-related genes and their implication in malignant melanoma susceptibility
Pigmentation-related genes and their implication in malignant melanoma susceptibility
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DOI：
10.1111/j.1600-0625.2009.00846.x
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发表时间：
2009-07-01
影响因子：
3.6
通讯作者：
Ribas, Gloria
中科院分区：
文献类型：
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作者：
Fernandez, Lara P.;Milne, Roger L.;Ribas, Gloria
人类色素沉着似乎是发展恶性黑色素瘤（MM）的个体风险的主要调节剂之一。已知大量基因参与稀有色素疾病，并解释了人类种群中色素沉着表型的大部分变化。这项西班牙病例对照研究包括205例黑色素瘤患者和245名对照组患者。主要与先天性色素沉着综合征相关的基因中的31个单核苷酸多态性（SNP）（ADTB3A，ATRN，CHS1，EDNRB，HPS，HPS，KIT，KIT，MGRN1，MITF，MITF，MITF，MITF，MLANA，MYO5A，MYO5A，MYO7A，MYO7A，OA1，OA1，OA1，OA1，OCA2，PAX3，pax3和pax3和pax3和pax3和SOX3和SOX3和SOX3和SOX3和SOX3和SOX3和SOX3和SOX3和SOX3和SOX3选择）。我们发现OCA2 R419Q（RS1800407）的变体等位基因与MM风险增加有关（OR 1.55，95％CI 1.04-2.31，p = 0.03）。这种对黑色素瘤风险的影响似乎在太阳凸甲或至少50个NEVI的个体中更强。我们还首次描述了与MyO7A基因中的变体S1666C（RS2276288）的关联（OR 1.35; 95％CI 1.04-1.76; P = 0.03）。同样，这种关联在几个表型群体中似乎更强，例如皮肤晴朗的人和童年晒伤的人。我们还发现，所认为的色素沉着基因中的几种变体与中间表型特征有关。我们的发现凸显了色素沉着基因在零星MM敏感性中的潜在重要性。
Human pigmentation appears to be one of the main modulators of individual risk of developing malignant melanoma (MM). A large number of genes are known to be involved in rare pigmentary disorders and explain most of the variation in pigmentation phenotypes seen in human populations. This Spanish case-control study included 205 patients with melanoma and 245 control subjects. Thirty-one single nucleotide polymorphisms (SNPs) in genes that had been mainly associated with congenital pigmentation syndromes (ADTB3A, ATRN, CHS1, EDNRB, HPS, KIT, MGRN1, MITF, MLANA, MYO5A, MYO7A, OA1, OCA2, PAX3 and SOX10) were selected. We found that the variant allele of OCA2 R419Q (rs1800407) was associated with increased risk of MM (OR 1.55, 95% CI 1.04-2.31, P = 0.03). This effect on melanoma risk appeared to be stronger among individuals with solar lentigines, or at least 50 nevi. We also describe, for the first time, an association with the variant S1666C (rs2276288) in the MYO7A gene (OR 1.35; 95% CI 1.04-1.76; P = 0.03). Again, this association appeared to be stronger in several phenotypic groups such as individuals with fair skin and those with childhood sunburns. We also found that several variants in the pigmentation genes considered were associated with intermediate phenotypic characteristics. Our findings highlight the potential importance of pigmentation genes in sporadic MM susceptibility.