Multiple pigmentation gene polymorphisms account for a substantial proportion of risk of cutaneous malignant melanoma.
Multiple pigmentation gene polymorphisms account for a substantial proportion of risk of cutaneous malignant melanoma.
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DOI：
10.1038/jid.2009.258
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发表时间：
2010-02
影响因子：
6.5
通讯作者：
Montgomery, Grant W.
中科院分区：
文献类型：
--
作者：
Duffy, David L.;Zhao, Zhen Z.;Sturm, Richard A.;Hayward, Nicholas K.;Martin, Nicholas G.;Montgomery, Grant W.
我们之前已经描述了红头发（黑素皮质素1受体，MC1R）和蓝眼睛（2型眼皮肤白化病，OCA2）基因多态性在高度暴露于阳光下的欧洲血统人群中调节皮肤恶性黑色素瘤（CMM）风险的作用。最近的一些研究，包括全基因组关联研究（GWAS），已经发现了许多控制人类头发、眼睛和皮肤颜色的多态性。在本文中，我们在一项基于澳大利亚人群的病例对照研究中，测试了色素沉着位点（ASIP， TYR, TYRP1, MC1R, OCA2, IRF4, SLC24A4, SLC45A2）的一组选择多态性与CMM风险的关联。IRF4和SLC24A4的变异，尽管在我们的样本中与色素沉着密切相关，但并没有改变CMM的风险，但其他六种变异却改变了。MATP基因（SLC45A2）中的三个snp （rs28777, rs35391, rs16891982）与风险表现出最强的粗相关性，但通过控制病例和对照组的祖先，这种相关性减弱到与MC1R红发色等位基因的效应大小大致相同。我们还发现SLC45A2和OCA2等位基因、MC1R和ASIP等位基因之间存在显著的上位性相互作用。总的来说，这些测量的变异占我们人群中CMM家族风险的12%。
We have previously described the role of red hair (Melanocortin 1 Receptor, MC1R) and blue eye (Oculocutaneous Albinism Type 2, OCA2) gene polymorphisms in modulating risk of cutaneous malignant melanoma (CMM) in a highly sun-exposed population of European descent. A number of recent studies, including genome-wide association studies (GWAS), have identified numerous polymorphisms controlling human hair, eye and skin colour. In this paper, we test a selected set of polymorphisms in pigmentation loci (ASIP, TYR, TYRP1, MC1R, OCA2, IRF4, SLC24A4, SLC45A2) for association with CMM risk in a large Australian population-based case control study. Variants in IRF4 and SLC24A4, despite being strongly associated with pigmentation in our sample, did not modify CMM risk, but the other six did. Three SNPs (rs28777, rs35391, rs16891982) in the MATP gene (SLC45A2) exhibited the strongest crude association with risk, but this was attenuated to approximately the same effect size as that of a MC1R red hair color allele by controlling for ancestry of cases and controls. We also detected significant epistatic interactions between SLC45A2 and OCA2 alleles, and MC1R and ASIP alleles. Overall, these measured variants account for 12% of the familial risk of CMM in our population.
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DOI：
10.1375/twin.7.1.98
发表时间：
2004-02-01
期刊：
TWIN RESEARCH
影响因子：
--
作者：
Do, KA;Aitken, JF;Martin, NG
通讯作者：
Martin, NG
影响因子：
9.8
作者：
Palmer, JS;Duffy, DL;Sturm, RA
通讯作者：
Sturm, RA
影响因子：
10.3
作者：
Aitken, J;Welch, J;Hayward, N
通讯作者：
Hayward, N
影响因子：
5.2
作者：
Jannot, AS;Meziani, R;Melan-Cohort
通讯作者：
Melan-Cohort
影响因子：
9.8
作者：
Kayser, Manfred;Liu, Fan;van Duijn, Cornelia M.
通讯作者：
van Duijn, Cornelia M.