Genomics Research Centre, Griffith Health Institute, Griffith University, Gold Coast, Australia.
Gene. 2011 Aug 15;482(1-2):68-72. doi: 10.1016/j.gene.2011.05.001. Epub 2011 May 13.
NCOA3 is a known low to moderate-risk breast cancer susceptibility gene, amplified in 5-10% and over expressed in about 60% of breast tumours. Additionally, this over expression is associated with Tamoxifen resistance and poor prognosis. Previously, two variants of NCOA3, 1758G>C and 2880A>G have been associated with breast cancer in two independent populations. Here we assessed the influence of the two NCOA3 variants on breast cancer risk by genotyping an Australian case-control study population. 172 cases and 178 controls were successfully genotyped for the 1758G>C variant and 186 cases and 182 controls were successfully genotyped for the 2880A>G variant using high-resolution melt analysis (HRM). The genotypes of the 1758G>C variant were validated by sequencing. χ(2) tests were performed to determine if significant differences exist in the genotype and allele frequencies between the cases and controls. χ(2) analysis returned no statistically significant difference (p>0.05) for genotype frequencies between cases and controls for 1758G>C (χ(2)=0.97, p=0.6158) or 2880A>G (χ(2)=2.09, p=0.3516). Similarly, no statistical difference was observed for allele frequencies for 1758G>C (χ(2)=0.07, p=0.7867) or 2880A>G (χ(2)=0.04, p=0.8365). Haplotype analysis of the two SNPs also showed no difference between the cases and the controls (p=0.9585). Our findings in an Australian Caucasian population composed of breast cancer sufferers and an age matched control population did not support the findings of previous studies demonstrating that these markers play a significant role in breast cancer susceptibility. Here, no significant difference was detected between breast cancer patients and healthy matched controls by either the genotype or allele frequencies for the investigated variants (all p ≥ 0.05). While an association of the two variants and breast cancer was not detected in our case-control study population, exploring these variants in a larger population of the same kind may obtain results in concordance with previous studies. Given the importance of NCOA3 and its involvement in biological processes involved in breast cancer and the possible implications variants of the gene could have on the response to Tamoxifen therapy, NCOA3 remains a candidate for further investigations.
NCOA3 是一种已知的低至中度风险的乳腺癌易感性基因，在 5-10%的乳腺癌中扩增，在约 60%的乳腺癌肿瘤中过度表达。此外，这种过度表达与他莫昔芬耐药和预后不良有关。先前，两种 NCOA3 变体 1758G>C 和 2880A>G 已在两个独立的人群中与乳腺癌相关联。在这里，我们通过对澳大利亚病例对照研究人群进行基因分型来评估这两种 NCOA3 变体对乳腺癌风险的影响。成功对 172 例病例和 178 例对照进行了 1758G>C 变体的基因分型，对 186 例病例和 182 例对照进行了 2880A>G 变体的基因分型，使用高分辨率熔解分析 (HRM)。通过测序验证了 1758G>C 变体的基因型。使用 χ(2)检验确定病例和对照组之间基因型和等位基因频率是否存在显著差异。χ(2)分析对于 1758G>C（χ(2)=0.97，p=0.6158）或 2880A>G（χ(2)=2.09，p=0.3516）的基因型频率，病例和对照组之间没有统计学意义上的差异（p>0.05）。同样，对于 1758G>C（χ(2)=0.07，p=0.7867）或 2880A>G（χ(2)=0.04，p=0.8365）的等位基因频率也未观察到统计学差异。对这两个 SNP 的单倍型分析也显示病例与对照组之间无差异（p=0.9585）。我们在由乳腺癌患者和年龄匹配的对照组组成的澳大利亚白种人群中的发现不支持先前研究的发现，即这些标记物在乳腺癌易感性中起重要作用。在这里，通过基因型或等位基因频率，未检测到研究变体在乳腺癌患者和健康匹配对照组之间存在差异（均 p≥0.05）。尽管在我们的病例对照研究人群中未检测到两种变体与乳腺癌之间的关联，但在同一人群中研究这些变体可能会获得与先前研究一致的结果。鉴于 NCOA3 的重要性及其在乳腺癌中涉及的生物学过程及其基因变异可能对他莫昔芬治疗反应的影响，NCOA3 仍然是进一步研究的候选对象。
