Department of Hygiene Toxicology, School of Public Health, Zunyi Medical University.
Department of Preventive Medicine, Guizhou Province Preventive Medicine Experimental Teaching Demonstration Centre, Zunyi, Guizhou.
Eur J Cancer Prev. 2023 Sep 1;32(5):450-459. doi: 10.1097/CEJ.0000000000000800. Epub 2023 Apr 10.
Cytochrome P450 1B1 ( CYP1B1 ) genetic variants are relevant in the pathogenesis of breast cancer. Exploring the relationships between CYP1B1 functional variants and breast cancer could improve our understanding of breast cancer molecular pathophysiology.
This is a two-stage hospital-based case-control study of a Chinese Han population. Genotyping was performed to identify candidate gene variants. 3DSNP, ANNOVAR, and RegulomeDB were used to determine functional single nucleotide polymorphisms (SNPs). The relationship between candidate variants and breast cancer risk was evaluated through unconditional logistic regression analysis. The PancanQTL platform was used to perform cis and trans expression quantitative trait loci (eQTL) analysis of positive SNPs. The GSCA platform was then used to compare the gene expression levels of potential target genes between breast cancer tissue and normal tissue adjacent to the cancer.
rs10175368-T acted as a protective factor against breast cancer based on an additive model [odds ratio (OR) = 0.722, 95% confidence interval (CI) = 0.613-0.850; P < 0.001], and was identified as a protective factor in the postmenopausal population (OR = 0.601; 95% CI, 0.474-0.764; P < 0.001). eQTL analysis and analysis of differential expression in carcinoma and paracancerous tissues revealed that the expression level of CYP1B1 - AS1 was associated with rs10175368 and that CYP1B1-AS1 had significantly higher expression levels in breast cancer tissues than in paracancerous tissues.
We show, for the first time in a Chinese Han population, that the functional variant rs10175368 plays a protective role against breast cancer, especially in the postmenopausal population.
细胞色素 P450 1B1（CYP1B1）基因变异与乳腺癌的发病机制有关。探索 CYP1B1 功能变异与乳腺癌之间的关系，可以增进我们对乳腺癌分子病理生理学的理解。
这是一项在中国汉族人群中进行的两阶段基于医院的病例对照研究。通过基因分型鉴定候选基因变异。3DSNP、ANNOVAR 和 RegulomeDB 用于确定功能单核苷酸多态性（SNP）。通过非条件逻辑回归分析评估候选变异与乳腺癌风险的关系。PancanQTL 平台用于对阳性 SNP 进行顺式和反式表达数量性状基因座（eQTL）分析。然后使用 GSCA 平台比较潜在靶基因在乳腺癌组织和癌旁正常组织中的基因表达水平。
基于加性模型，rs10175368-T 可作为乳腺癌的保护因素[比值比（OR）=0.722，95%置信区间（CI）=0.613-0.850；P<0.001]，且在绝经后人群中被鉴定为保护因素（OR=0.601；95%CI，0.474-0.764；P<0.001）。eQTL 分析和癌组织与癌旁组织差异表达分析表明，CYP1B1-AS1 的表达水平与 rs10175368 相关，且 CYP1B1-AS1 在乳腺癌组织中的表达水平明显高于癌旁组织。
我们首次在中国汉族人群中表明，功能变异 rs10175368 对乳腺癌具有保护作用，尤其是在绝经后人群中。
