A novel polymorphism in the 1A promoter region of the vitamin D receptor is associated with altered susceptibilty and prognosis in malignant melanoma.
A novel polymorphism in the 1A promoter region of the vitamin D receptor is associated with altered susceptibilty and prognosis in malignant melanoma.
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DOI：
10.1038/sj.bjc.6602006
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发表时间：
2004-08-16
影响因子：
8.8
通讯作者：
中科院分区：
文献类型：
--
作者：
The association of Taq 1 and Fok 1 restriction fragment length polymorphisms of the vitamin D receptor with occurrence and outcome of malignant melanoma (MM), as predicted by tumour (Breslow) thickness, has been reported previously. We now report a novel adenine–guanine substitution −1012 bp relative to the exon 1a transcription start site (A-1012G), found following screening by single-stranded conformational polymorphism of this promoter region. There was a total of 191 MM cases , which were stratified according to conventional Breslow thickness groups, cases being randomly selected from each group to form a distribution corresponding to the known distribution of Breslow thickness in our area, and this population (n=176) was compared to 80 controls. The A allele was over-represented in MM patients and, with GG as reference, odds ratio (OR) for AG was 2.5, 95% confidence interval (CI) 1.1–5.7, (P=0.03) and AA 3.3, CI 1.4–8.1, (P=0.007). The outcome was known in 171 of 191 patients and the A allele was related to the development of metastasis, the Kaplan–Meier estimates of the probability of metastasis at 5 years being: GG 0%; AG 9%, CI 4–16%; AA 21%, CI 12–36%; (P=0.008), and to thicker Breslow thickness groups (P=0.04). The effect on metastasis was independent of tumour thickness and A-1012G may have predictive potential, additional to Breslow thickness. Neither the Fok 1 nor Taq 1 variants (f and t) were significantly related to the development of metastasis, although there was a strong relationship of fftt with the thickest Breslow thickness group (P=0.005). There was an interaction between the A-1012G and Fok 1 polymorphisms (P=0.025) and the Fok 1 variant enhanced the effect of the A allele of the A-1012G polymorphism on metastasis, the probability of metastasis for AAff at 5 years follow-up being 57%, CI 24–92%.
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影响因子：
1.6
作者：
Hamasaki, T;Inatomi, H;Matsumoto, T
通讯作者：
Matsumoto, T
影响因子：
4.4
作者：
Boonstra, A;Barrat, FJ;O'Garra, A
通讯作者：
O'Garra, A
影响因子：
2.8
作者：
Bodiwala, D;Luscombe, CJ;Strange, RC
通讯作者：
Strange, RC
影响因子：
4.7
作者：
Dunning, AM;McBride, S;Ponder, BAJ
通讯作者：
Ponder, BAJ
影响因子：
2
作者：
Hamasaki, T;Inatomi, H;Matsumoto, T
通讯作者：
Matsumoto, T