Molecular Pharmacology Section, Medical Oncology Branch, Center for Cancer Research, Bethesda, Maryland, USA.
BMJ Open. 2013 Jan 3;3(1):e002030. doi: 10.1136/bmjopen-2012-002030.
Although it does not alter the ERCC1 phenotype, the ERCC1 500C>T (rs11615) polymorphism has undergone a myriad of investigations into its role as a marker for nucleotide excision repair (NER) function in different races, diseases and treatment outcomes. The goal of our study was to test the hypothesis that 500C>T is in linkage disequilibrium (LD) with causative alleles, and that these haplotypes are more frequent in Caucasians with melanoma than in healthy Caucasians or African Americans.
In this case-control study, we selected race-specific ERCC1 single-nucleotide polymorphism (SNPs), conducted LD analysis with ERCC1 500C>T and compared the frequency of ERCC1 diplotypes in Caucasians with melanoma (n=165), healthy Caucasians (n=150) and healthy African Americans (n=159). The haplotype was further studied using a fusion gene containing multiple ERCC1 SNPs.
Large cancer institute in the USA.
A total of 165 Caucasian melanoma patients, 159 healthy Caucasian controls and 159 African American healthy controls. Men and women were enrolled in the clinical trial; however, since the screening trial included prostate cancer screening in addition to screening for other cancers, only male controls were available.
The outcome measures were melanoma risk in Caucasians, and LD between ERCC1 SNP, N118N and other race-specific allelic variants.
When compared to ERCC1 500C>T alone, a race-specific three-SNP variant haplotype in ERCC1 (comprised of rs11615, rs3212950 and rs3212948) was even more frequent in Caucasians with melanoma than in healthy Caucasians (p=0.0034) or African Americans (p<0.0001). A plasmid containing the variant haplotype was not differentially expressed.
We demonstrate that ERCC1 500C>T participates in a previously characterised cancer-risk haplotype found more frequently in Caucasians, while LD is weak in African Americans; this haplotype appears to also be related to melanoma. It is therefore likely that ERCC1 500C>T is only a valid NER, disease or treatment outcome marker in Caucasians.
尽管 ERCC1 500C>T（rs11615）多态性不会改变 ERCC1 表型，但它在不同种族、疾病和治疗结果中作为核苷酸切除修复（NER）功能标志物的作用已经进行了大量研究。我们研究的目的是检验假设，即 500C>T 与致病等位基因呈连锁不平衡（LD），并且这些单倍型在患有黑色素瘤的白种人中比在健康的白种人和非裔美国人中更为常见。
在这项病例对照研究中，我们选择了种族特异性的 ERCC1 单核苷酸多态性（SNP），与 ERCC1 500C>T 进行 LD 分析，并比较了黑色素瘤患者（n=165）、健康白种人（n=150）和健康非裔美国人（n=159）中 ERCC1 二倍型的频率。使用包含多个 ERCC1 SNP 的融合基因进一步研究了单倍型。
美国大型癌症研究所。
共纳入 165 例白种人黑色素瘤患者、159 例健康白种人对照和 159 例健康非裔美国人对照。男性和女性均参加了临床试验；然而，由于筛选试验除了筛查其他癌症外还包括前列腺癌筛查，因此只有男性对照可用。
结局测量为白种人黑色素瘤的风险，以及 ERCC1 SNP、N118N 和其他种族特异性等位基因变异之间的 LD。
与 ERCC1 500C>T 单独比较时，ERCC1 中由 rs11615、rs3212950 和 rs3212948 组成的种族特异性三 SNP 变体单倍型在黑色素瘤患者中的频率甚至高于健康白种人（p=0.0034）或非裔美国人（p<0.0001）。含有变体单倍型的质粒表达没有差异。
我们证明 ERCC1 500C>T 参与了先前在白种人中发现的与癌症风险相关的单倍型，而在非裔美国人中 LD 较弱；该单倍型似乎也与黑色素瘤有关。因此，ERCC1 500C>T 很可能仅在白种人中是有效的 NER、疾病或治疗结果标志物。
