胸基质淋球生成素的表达和等位基因频率是乳腺癌风险的关键因素。
Expression and allele frequencies of Thymic stromal lymphopoietin are a key factor of breast cancer risk.
机构信息
Groupe de Recherche en Écologie Buccale, Faculté de Médecine Dentaire, Université Laval, Québec, Canada.
Department of Biochemistry, College of Science King Saud University, Riyadh, Kingdom of Saudi Arabia.
出版信息
Mol Genet Genomic Med. 2019 Aug;7(8):e813. doi: 10.1002/mgg3.813. Epub 2019 Jun 17.
BACKGROUND
Thymic stromal Lymphopoeitin (TSLP) is a key cytokine involved in inflammation and cancer progression. TSLP gene polymorphisms have been associated with increased susceptibility to cancer progression in different organs. We performed a control case study to examine the correlation of expression and polymorphisms of three nucleotides in TSLP with breast cancer (BC) risk in Saudi Arabian females.
MATERIALS AND METHODS
The study was conducted on 116 healthy control subjects and 127 female patients with BC for the purpose of genotyping. Ten matching tissues provided data on immunohistochemistry to evaluate TSLP expression. Three SNPs (rs10043985, rs2289276, and rs3806933) were genotyped with TaqMan allelic discrimination assay. The patients' ages and estrogen receptor statuses were used to investigate the potential correlations between the different variations of TSLP genotypes and BC risk.
RESULTS
BC tissues expressed positive immuno-staining for TSLP at a high rate compared to normal matching breast tissues. Malignant breast tumors exhibited higher TSLP expression than benign breast tumors. We also found that the rs3806933 (T) allele frequency decreased the risk of developing BC in the study population (OR = 0.356, p = 0.00027) significantly (0.356 times). Interestingly, statistical analysis revealed that the genotype mutant (AC) and the allele mutant (C) of rs10043985 within TSLP were significantly correlated with an increased BC risk (odds ratio [OR] = 4.762, confidence interval [CI] = 1.000-22.666, p = 0.03244; OR = 4.762, CI = 1.000-22.666, p = 0.03244; and OR = 4.575, CI = 0.975-21.464, p = 0.03516, respectively). In addition, the AC and AC + CC genotypes of TSLP rs10043985 were confirmed to be associated with an increased risk of BC risk in women aged above 48 years, compared with the AA genotype (AC and AC + CC vs. AA: OR = 9.468, CI = 0.493-181.768, p = 0.04537).
CONCLUSION
The results reveal significant correlation between SNPs in TSLP and BC progression in Saudi Arabian female patients.
背景
胸腺基质淋巴细胞生成素（TSLP）是一种参与炎症和癌症进展的关键细胞因子。TSLP 基因多态性与不同器官中癌症进展的易感性增加有关。我们进行了一项对照病例研究，以检查 TSLP 中三个核苷酸的表达和多态性与沙特阿拉伯女性乳腺癌（BC）风险的相关性。
材料和方法
该研究对 116 名健康对照受试者和 127 名 BC 女性患者进行了基因分型。十对匹配组织提供了免疫组化数据，以评估 TSLP 的表达。采用 TaqMan 等位基因鉴别检测法对三个 SNP(rs10043985、rs2289276 和 rs3806933)进行基因分型。患者的年龄和雌激素受体状态用于研究 TSLP 基因型的不同变化与 BC 风险之间的潜在相关性。
结果
与正常匹配的乳腺组织相比，BC 组织中 TSLP 的免疫染色呈高阳性率。恶性乳腺肿瘤的 TSLP 表达高于良性乳腺肿瘤。我们还发现，rs3806933（T）等位基因频率显著降低了研究人群中发生 BC 的风险（OR=0.356，p=0.00027）（0.356 倍）。有趣的是，统计学分析显示，TSLP 内 rs10043985 的突变基因型（AC）和突变等位基因（C）与 BC 风险增加显著相关（优势比[OR]=4.762，置信区间[CI]=1.000-22.666，p=0.03244；OR=4.762，CI=1.000-22.666，p=0.03244；OR=4.575，CI=0.975-21.464，p=0.03516）。此外，rs10043985 的 AC 和 AC+CC 基因型与 48 岁以上女性的 BC 风险增加相关，与 AA 基因型相比（AC 和 AC+CC 与 AA：OR=9.468，CI=0.493-181.768，p=0.04537）。
结论
结果表明 TSLP 中的 SNP 与沙特阿拉伯女性患者的 BC 进展之间存在显著相关性。
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