The pattern of clinical breast cancer metastasis correlates with a single nucleotide polymorphism in the C1qA component of complement
The pattern of clinical breast cancer metastasis correlates with a single nucleotide polymorphism in the C1qA component of complement
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DOI：
10.1007/s00251-005-0077-y
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发表时间：
2006-02-01
期刊：
影响因子：
3.2
通讯作者：
Weiner, GJ
中科院分区：
文献类型：
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作者：
Racila, E;Racila, DM;Weiner, GJ
补体是针对血管内微生物的主要防御机制之一，可以在针对恶性肿瘤的免疫反应及其临床行为中发挥作用。我们评估了 C1qA 的唯一编码多态性是否与乳腺癌患者的预后相关。在 63 名患有局限性肿瘤的乳腺癌受试者中进行了 C1qA([276A/G]) 的基因分型，并与 38 名患有转移的乳腺癌受试者进行了比较。在多变量分析中考虑和评估了临床结果的既定危险因素。具有杂合或纯合 C1qA([276G]) 基因型的乳腺癌受试者比具有纯合 C1qA([276A]) 基因型的受试者具有更高的转移率 [风险比 (HR) 2.4，95% 置信区间 (CI) 1.1-4.1]。当仅考虑与血行扩散相关的转移部位（即骨、肝和脑）时，这种相关性更强（HR 3.5，95% CI 1.4-5.6），并且在调整阳性淋巴结数量、雌激素受体状态和孕激素受体状态后，这种相关性仍然具有统计学意义。所有乳腺癌受试者和对照组之间的 C1qA([276A/G]) 等位基因分布没有统计学差异。这些结果表明，补体 C1qA 成分第 276 位的单核苷酸多态性可能与乳腺癌转移至与疾病的血行传播相关的位点有关。与远处转移减少相关的 C1qA 多态性也与皮下系统性狼疮和 C1q 缺陷的发病率增加相关，这表明免疫反应的改变可能在观察到的关联中发挥作用。
Complement is one of primary defense mechanisms against intravascular microorganisms and could play a role in the immune response to malignancy and hence its clinical behavior. We evaluated if the sole coding polymorphism of C1qA associates with outcome in patients with breast carcinoma. Genotyping for C1qA([276A/G]) was performed in 63 breast cancer subjects with localized tumor and compared with that in 38 breast cancer subjects with metastasis. Established risk factors for clinical outcome were considered and evaluated in multivariable analysis. Breast cancer subjects with heterozygous or homozygous C1qA([276G]) genotype had a higher rate of metastasis than subjects with the homozygous C1qA([276A]) genotype [hazard ratio (HR) 2.4, 95% confidence interval (CI) 1.1-4.1]. This association was stronger when only metastatic sites associated with hematogenous spread, i.e., to the bone, liver, and brain, were considered (HR 3.5, 95% CI 1.4-5.6) and remained statistically significant after adjustment for the number of positive lymph nodes, estrogen receptor status, and progesterone receptor status. There was no statistical difference in the C1qA([276A/G]) allelic distribution between all subjects with breast cancer and controls. These results suggest there could be an association of a single nucleotide polymorphism at position 276 of the C1qA component of complement with breast cancer metastasis to sites linked to hematogenous spread of disease. The C1qA polymorphism associated with decreased distant metastasis has also been correlated with an increased incidence of subcutaneous systemic lupus and C1q deficiencies, suggesting that an altered immune response may play a role in the observed association.