Zhao Duanchong, Yu Xingxing, Huang Hongli, Zou Shuqing, Zhu Pingxiu, Lin Yuxiang, Song Mengjie, Fu Fangmeng, Yang Haomin
Department of Epidemiology and Health Statistics, School of Public Health, Fujian Medical University, Fuzhou, China.
Department of Operation and Supervision, Jining Customs of the People's Republic of China, Jining, China.
Front Oncol. 2024 Dec 5;14:1475979. doi: 10.3389/fonc.2024.1475979. eCollection 2024.
Chemokines are well-known for playing an essential role in the development of cancer. However, the association between SNPs in the CCL2 and CXCL12 genes and the susceptibility to breast cancer remains unclear.
A case-control study was conducted in southeast China, including 1855 breast cancer patients and 1838 cancer-free controls. The association between single nucleotide polymorphisms (SNPs) in the CCL2 and CXCL12 genes and the susceptibility to breast cancer was investigated using logistic regression models. The association between plasma CCL2 and CXCL12 with breast cancer was further examined in 72 patients and 75 controls.
The CXCL12 SNP rs3740085 was associated with breast cancer in the additive model (OR=1.15, 95%CI=1.01-1.32), particularly in postmenopausal women. The association between rs1024611 in CCL2 and breast cancer was only found in women with a BMI of ≥24kg/m2. SNPs in the CCL2 gene were mainly associated with PR-positive breast cancer, whereas rs1144471 in CXCL12 was associated with ER-negative (OR=0.43, 95% CI=0.23-0.84), PR-negative (OR=0.38, 95% CI=0.19-0.74), and HER-2-positive (OR=1.27, 95% CI=1.03-1.56) breast cancer. The interaction between rs1801157 and rs3740085 in CXCL12 SNPs was statistically significant, and rs3740085 was also associated with breast cancer survival. Additionally, we found a strong association between plasma CXCL12 and breast cancer.
CCL2 and CXCL12 SNPs are associated with breast cancer susceptibility in overweight and postmenopausal women, and the effect varies according to subtypes. The interaction of SNPs within CXCL12 gene and the association with breast cancer survival further suggest potential targets for improved risk assessment and treatment strategies.
趋化因子在癌症发展过程中发挥重要作用，这一点广为人知。然而，CCL2和CXCL12基因中的单核苷酸多态性（SNP）与乳腺癌易感性之间的关联仍不明确。
在中国东南部开展了一项病例对照研究，纳入1855例乳腺癌患者和1838例无癌对照。使用逻辑回归模型研究CCL2和CXCL12基因中的单核苷酸多态性（SNP）与乳腺癌易感性之间的关联。在72例患者和75例对照中进一步研究血浆CCL2和CXCL12与乳腺癌之间的关联。
在加性模型中，CXCL12 SNP rs3740085与乳腺癌相关（OR = 1.15，95%CI = 1.01 - 1.32），尤其在绝经后女性中。CCL2中的rs1024611与乳腺癌的关联仅在体重指数（BMI）≥24kg/m²的女性中发现。CCL2基因中的SNP主要与孕激素受体（PR）阳性乳腺癌相关，而CXCL12中的rs1144471与雌激素受体（ER）阴性（OR = 0.43，95%CI = 0.23 - 0.84）、PR阴性（OR = 0.38，95%CI = 0.19 - 0.74）和人表皮生长因子受体2（HER-2）阳性（OR = 1.27，95%CI = 1.03 - 1.56）乳腺癌相关。CXCL12 SNP中的rs1801157与rs3740085之间的相互作用具有统计学意义，且rs3740085也与乳腺癌生存相关。此外，我们发现血浆CXCL12与乳腺癌之间存在强关联。
CCL2和CXCL12 SNP与超重和绝经后女性的乳腺癌易感性相关，且效应因亚型而异。CXCL12基因内SNP的相互作用以及与乳腺癌生存的关联进一步提示了改善风险评估和治疗策略的潜在靶点。
