Department of Breast Surgical Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China.
Department of Breast Surgical Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China; School of Clinical Medicine, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100005, China.
Gene. 2023 Oct 30;884:147676. doi: 10.1016/j.gene.2023.147676. Epub 2023 Jul 29.
Breast cancer is a complex disease influenced by both external and internal factors, among which genetic factors play a critical role. Single-nucleotide polymorphisms (SNPs) are major contributors to the heritability of breast cancer, and their frequencies vary across ethnic groups. In this study, we aimed to investigate the association between 34 SNPs identified in previous genome-wide association studies (GWAS) and overall breast cancer risk, as well as breast cancer subtypes, in the Chinese female population. To accomplish this, we conducted an extensive association analysis using the high-throughput Sequenom MassARRAY® platform in a case-control study comprising 1848 breast cancer patients and 709 healthy controls. Our analysis, which utilized the SNPassoc package in R based on chi-squared (χ2) test and genetic model analysis, identified significant associations between breast cancer risk and SNP rs12493607 (TGFBR2, risk allele C, OR = 1.28 [1.11-1.47], P = 0.0005), as well as a less conservatively significant association with rs4784227 (CASC16, risk allele T, OR = 1.24 [1.08-1.42], P = 0.0017) and rs2046210 (ESR1, risk allele A, OR = 1.50 [1.16-1.95], P = 0.0016). Furthermore, our stratified analyses revealed that rs12493607 was significantly associated with invasive carcinoma, estrogen receptor (ER)-positive, progesterone receptor (PR)-positive, HER2-negative, and young (aged younger than 45) breast cancer. SNP rs4784227 and rs3803662 (CASC16) were associated with invasive carcinoma and ER-positive breast cancer, while rs2046210 was linked to ductal carcinoma in situ, ER-negative, PR-negative, HER2-positive, and elder (aged more than 45) breast cancers. SNPs rs10484919 (ESR1) and rs1038304 (CCDC170) showed links to HER2-positive breast cancer, and rs616488 (PEX14) with premenopausal breast cancer. In summary, our study shed light on the relationship between SNPs and breast cancer susceptibility within a vast Chinese cohort, supporting the development of polygenetic risk scores for the Chinese population. These findings provide valuable insights into the genetic basis of breast cancer and have important implications for risk prediction, early detection, and personalized treatment of this disease.
乳腺癌是一种受内外因素影响的复杂疾病，其中遗传因素起着关键作用。单核苷酸多态性（SNP）是乳腺癌遗传的主要贡献者，其频率在不同种族之间存在差异。在这项研究中，我们旨在研究先前全基因组关联研究（GWAS）中确定的 34 个 SNP 与中国女性人群的总体乳腺癌风险以及乳腺癌亚型之间的关联。为了实现这一目标，我们使用高通量Sequenom MassARRAY®平台在病例对照研究中进行了广泛的关联分析，该研究包括 1848 名乳腺癌患者和 709 名健康对照。我们的分析利用了基于卡方（χ2）检验和遗传模型分析的 R 中的 SNPassoc 包，鉴定出与乳腺癌风险相关的 SNP rs12493607（TGFBR2，风险等位基因 C，OR = 1.28 [1.11-1.47]，P = 0.0005）以及与 rs4784227（CASC16，风险等位基因 T，OR = 1.24 [1.08-1.42]，P = 0.0017）和 rs2046210（ESR1，风险等位基因 A，OR = 1.50 [1.16-1.95]，P = 0.0016）之间存在不太保守的显著关联。此外，我们的分层分析表明，rs12493607 与浸润性癌、雌激素受体（ER）阳性、孕激素受体（PR）阳性、HER2 阴性和年轻（年龄小于 45 岁）乳腺癌显著相关。SNP rs4784227 和 rs3803662（CASC16）与浸润性癌和 ER 阳性乳腺癌相关，而 rs2046210 与导管原位癌、ER 阴性、PR 阴性、HER2 阳性和年龄较大（年龄大于 45 岁）乳腺癌相关。SNP rs10484919（ESR1）和 rs1038304（CCDC170）与 HER2 阳性乳腺癌相关，而 rs616488（PEX14）与绝经前乳腺癌相关。总之，我们的研究阐明了 SNP 与中国人群中乳腺癌易感性之间的关系，支持为中国人群开发多基因风险评分。这些发现为乳腺癌的遗传基础提供了有价值的见解，并对该疾病的风险预测、早期检测和个体化治疗具有重要意义。
