División de Genética, Centro de Investigación Biomédica de Occidente, Instituto Mexicano del Seguro Social, Guadalajara, Jalisco, México.
Eur Rev Med Pharmacol Sci. 2020 Oct;24(19):9990-10002. doi: 10.26355/eurrev_202010_23212.
The rs1008562, rs2234671 and rs3138060 polymorphisms of the CXCR1 gene have been shown to be associated with many diseases, but in breast cancer (BC) their association has not been detected. The purpose of this study was to determine the frequency and association of the rs1008562, rs2234671 and rs3138060 polymorphisms of CXCR1 gene in BC patients in the Mexican population.
The CXCR1 polymorphisms were determined by Polymerase Chain Reaction (PCR) and real time-PCR in healthy Mexican subjects and BC patients.
The prevalent patron in BC patients was observed, the majority were overweight and obesity (72%) with metastatic lymph nodes (48%), luminal A/B subtypes (63%), and advanced stages (60%). Triple negative breast cancer (TNBC) patients: they were younger (58%) than 43 years old, overweight (33%), obesity (42%), ductal type histological (98%), metastasis to lymph nodes (47%), advanced stages III-IV (61%) and metastasis (33%). The rs2234671 polymorphism was associated with BC susceptibility when BC patients and the control group were compared for the CC genotype (p=0.037), CG (heterozygous model: p=0.018), GC/CC (dominant model: p=0.004), and the C allele (p=0.001), as well as the GC/CC genotype with hormone replace therapy (HRT, p=0.016). The rs3138060 polymorphism was associated with BC susceptibility for CG/GG genotype (dominant model: p=0.032) and G allele (p=0.018). Although the association between the dominant model of rs1008562, rs2234671, rs3138060 polymorphisms and BC patients and control was evident for tobacco and alcohol consumption (p<0.05). The rs1008562, rs2234671, and rs3138060 polymorphisms of the CXCR1 gene classified by molecular subtype and stage were also associated with BC patients, indicating that these factors may significantly contribute to BC risk. The CCC (OR 1.75, 95% CI 1.03- 2.97, p=0.046), GGG (OR 3.73, 95% CI 1.61- 8.65, p=0.0018) haplotypes were also associated with BC susceptibility.
Rs2234671 and rs3138060 polymorphisms in the CXCR1 gene were associated with BC susceptibility in the Mexican population. The dominant model of the rs1008562, rs2234671 and rs3138060 polymorphisms could significantly contribute to BC risk in tobacco and alcohol consumption, molecular subtype and stage. The rs1008562, rs2234671 and rs3138060 polymorphisms, and the haplotypes CCC and GGG could significantly contribute to BC risk in the Mexican population analyzed.
CXCR1 基因的 rs1008562、rs2234671 和 rs3138060 多态性与许多疾病有关,但在乳腺癌 (BC) 中尚未检测到其相关性。本研究旨在确定 CXCR1 基因 rs1008562、rs2234671 和 rs3138060 多态性在墨西哥人群中 BC 患者中的频率和相关性。
通过聚合酶链反应 (PCR) 和实时 PCR 确定健康墨西哥受试者和 BC 患者的 CXCR1 多态性。
在 BC 患者中观察到常见的模式,大多数为超重和肥胖 (72%),伴有转移性淋巴结 (48%)、腔 A/B 亚型 (63%)和晚期 (60%)。三阴性乳腺癌 (TNBC) 患者:他们比 43 岁以下的患者更年轻 (58%),超重 (33%),肥胖 (42%),导管型组织学 (98%),淋巴结转移 (47%),晚期 III-IV 期 (61%)和转移 (33%)。与对照组相比,rs2234671 多态性与 BC 易感性相关,CC 基因型 (p=0.037)、CG (杂合子模型:p=0.018)、GC/CC (显性模型:p=0.004)和 C 等位基因 (p=0.001),GC/CC 基因型与激素替代治疗 (HRT,p=0.016)。rs3138060 多态性与 CG/GG 基因型 (显性模型:p=0.032)和 G 等位基因 (p=0.018)与 BC 易感性相关。尽管 rs1008562、rs2234671、rs3138060 多态性的显性模型与 BC 患者和对照组之间与烟草和酒精消费有关 (p<0.05)。CXCR1 基因的 rs1008562、rs2234671 和 rs3138060 多态性按分子亚型和分期分类也与 BC 患者相关,表明这些因素可能显著增加 BC 的风险。CCC (OR 1.75, 95% CI 1.03-2.97, p=0.046)、GGG (OR 3.73, 95% CI 1.61-8.65, p=0.0018) 单倍型也与 BC 易感性相关。
在墨西哥人群中,CXCR1 基因的 rs2234671 和 rs3138060 多态性与 BC 易感性相关。rs1008562、rs2234671 和 rs3138060 多态性的显性模型可显著增加烟草和酒精消费、分子亚型和分期的 BC 风险。rs1008562、rs2234671 和 rs3138060 多态性和 CCC 和 GGG 单倍型可显著增加分析的墨西哥人群中 BC 的风险。