Clinical Research Program, Department of Dermatology, Brigham and Women's Hospital, and Harvard Medical School, Boston, Massachusetts, USA.
Cancer Res. 2011 Mar 1;71(5):1533-9. doi: 10.1158/0008-5472.CAN-10-1818. Epub 2011 Jan 26.
Genome-wide association studies on pigmentary phenotypes provide a pool of candidate genetic markers for skin cancer risk. The SNPs identified from a genome-wide association study of natural hair color were assessed for associations with the risk of three types of skin cancer simultaneously in a nested case-control study within the Nurses' Health Study [218 melanoma, 285 squamous cell carcinoma (SCC), and 300 basal cell carcinoma (BCC) cases, and 870 common controls]. Along with two known pigmentation loci, MC1R and OCA2, the IRF4 rs12203592 T allele was associated with an increased risk of each type of skin cancer (P value, 6.6 × 10(-4) for melanoma, 7.0 × 10(-7) for SCC, and 0.04 for BCC). This association was further replicated in additional samples (190 melanoma, 252 SCC, and 634 common controls). The P value in the replication set was 0.03 for melanoma and 4.2 × 10(-3) for SCC. The risk of BCC was replicated in an independent set of 213 cases and 718 controls (P value, 0.02). The combined results showed that the association with SCC reached the genome-wide significance level [odds ratio (OR) for additive model = 1.61, 95%CI, 1.36-1.91, P = 3.2 × 10(-8)]. The OR was 1.49 for melanoma (95%CI, 1.23-1.80; P = 4.5 × 10(-5)), and 1.32 for BCC (95%CI, 1.11-1.57; P = 1.6 × 10(-3)). Given that the T allele was shown previously to be associated with increased expression of IRF4 locus, further studies are warranted to elucidate the role of the IRF4 gene in human pigmentation and skin cancer development.
全基因组关联研究对色素表型提供了一个候选遗传标记的皮肤癌风险。从全基因组关联研究的自然头发颜色确定的 SNPs 进行评估协会与三种类型的皮肤癌风险同时在巢式病例对照研究护士健康研究[218 黑色素瘤，285 鳞状细胞癌（SCC）和 300 基底细胞癌（BCC）的情况下，和 870 常见控件]。除了两个已知的色素沉着位点，MC1R 和 OCA2，IRF4 rs12203592 T 等位基因与每种类型的皮肤癌的风险增加相关（P 值，6.6×10(-4)黑色素瘤，7.0×10(-7)SCC 和 0.04 为 BCC）。这种关联在其他样本中进一步复制（190 例黑色素瘤，252 例 SCC 和 634 例常见对照）。在复制集中的 P 值为 0.03 为黑色素瘤和 4.2×10(-3)SCC。BCC 的风险在独立的一组 213 例和 718 例对照中得到复制（P 值，0.02）。综合结果表明，与 SCC 的关联达到了全基因组显著水平[加性模型的比值比（OR）= 1.61，95%CI，1.36-1.91，P = 3.2×10(-8)]。OR 为 1.49 为黑色素瘤（95%CI，1.23-1.80；P = 4.5×10(-5)），和 1.32 为 BCC（95%CI，1.11-1.57；P = 1.6×10(-3)）。鉴于 T 等位基因先前被证明与 IRF4 基因座的表达增加相关，进一步的研究需要阐明 IRF4 基因在人类色素沉着和皮肤癌发展中的作用。
