Division of Clinical Epidemiology, McGill University Health Centre, Montreal, Quebec, Canada.
Lupus. 2012 Jul;21(8):896-9. doi: 10.1177/0961203312443992. Epub 2012 Apr 11.
Recent work has demonstrated an important decrease in breast cancers for women with systemic lupus erythematosus (SLE). The reason behind this phenomenon is unknown. Our purpose was to explore whether the single nucleotide polymorphisms (SNPs) predisposing to SLE might be protective against breast cancer (in women in the general population).
We focused on loci relevant to 10 SNPs associated with SLE (with a p value of <10(-9)). We determined whether we could establish a decreased frequency of these SNPs in breast cancer cases versus controls, within the general population. To do this we used a large breast cancer genome-wide association study (GWAS) dataset, involving 3,659 breast cancer cases and 4,897 controls. These subjects were all primarily of European ancestry.
The population-based GWAS breast cancer data we examined suggested little evidence for important associations between breast cancer and SLE-related SNPs. Within the general population GWAS data, a cytosine(C) nucleotide substitution at rs9888739 (on chromosome 16p11.2) showed a very weak inverse association with breast cancer. The odds ratio (OR) for the rs9888739-C allele was 0.907551 (p value 0.049899) in the GWAS breast cancer sample, compared to controls. There was a slightly stronger, positive, association with breast cancer for rs6445975-G (Guanine) on chromosome 3p14.3, with a breast cancer OR of 1.0911 (p value 0.0097).
Within this large breast cancer dataset, we did not demonstrate important associations with 10 lupus-associated SNPs. If decreased breast cancer risk in SLE is influenced by genetic profiles, this may be due to complex interactions and/or epigenetic factors.
最近的研究表明，系统性红斑狼疮（SLE）患者的乳腺癌发病率显著降低。这种现象的原因尚不清楚。我们的目的是探讨导致 SLE 的单核苷酸多态性（SNP）是否可能对乳腺癌（一般人群中的女性）具有保护作用。
我们专注于与 SLE 相关的 10 个 SNP（p 值<10(-9)）相关的基因座。我们确定是否可以在一般人群中建立乳腺癌病例与对照之间这些 SNP 频率降低的关系。为此，我们使用了一个大型乳腺癌全基因组关联研究（GWAS）数据集，其中包括 3659 例乳腺癌病例和 4897 例对照。这些受试者主要来自欧洲血统。
我们研究的基于人群的 GWAS 乳腺癌数据表明，乳腺癌与 SLE 相关 SNP 之间的关联几乎没有重要证据。在一般人群的 GWAS 数据中，位于 16p11.2 上的 rs9888739 的胞嘧啶（C）核苷酸取代与乳腺癌呈微弱的反向关联。与对照相比，rs9888739-C 等位基因在 GWAS 乳腺癌样本中的比值比（OR）为 0.907551（p 值 0.049899）。位于 3p14.3 上的 rs6445975-G（鸟嘌呤）与乳腺癌呈略微更强的正相关，乳腺癌 OR 为 1.0911（p 值 0.0097）。
在这个大型乳腺癌数据集内，我们没有发现 10 个狼疮相关 SNP 与乳腺癌有重要关联。如果 SLE 中乳腺癌风险降低受到遗传特征的影响，这可能是由于复杂的相互作用和/或表观遗传因素所致。
