在一项病例对照研究中，KIAA基因的潜在功能变异与乳腺癌风险相关。

Potential functional variants of KIAA genes are associated with breast cancer risk in a case control study.

作者信息

Zhou Jing, Chen Congcong, Liu Sijun, Zhou Wen, Du Jiangbo, Jiang Yue, Dai Juncheng, Jin Guangfu, Ma Hongxia, Hu Zhibin, Chen Jiaping, Shen Hongbing

机构信息

Department of Epidemiology, International Joint Research Center on Environment and Human Health, Center for Global Health, School of Public Health, Nanjing Medical University, Nanjing, China.

Statistical Center, Information Department, Northern Jiangsu People's Hospital and Clinical Medical College of Yangzhou University, Yangzhou, China.

出版信息

Ann Transl Med. 2021 Apr;9(7):549. doi: 10.21037/atm-20-6108.

DOI:10.21037/atm-20-6108

PMID:33987247

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8105804/

Abstract

BACKGROUND

KIAA genes identified in the Kazusa cDNA-sequencing project may play important roles in biological processes and are involved in carcinogenesis of many cancers. Genetic variants of KIAA genes are implicated in the abnormal expression of these genes and are linked to susceptibility of several human complex diseases.

METHODS

The differentially expressed KIAA genes were screened and identified in The Cancer Genome Atlas (TCGA) database of breast cancer. A total of 48 variants located in the 28 KIAA genes were selected to investigate the associations between polymorphism and breast cancer in 1,032 cases and 1,063 cancer-free controls in a Chinese population.

RESULTS

Two coding variants, which included a SNP rs2306369 in and a SNP rs1205434 in , were identified to be associated with the incidences of breast cancer. Logistic regression analysis showed that the SNP rs2306369 G allele was associated with a decreased risk of breast cancer (additive model: OR =0.81, 95% CI: 0.66-0.99, P=0.038), whereas the SNP rs1205434 A allele was involved with a higher risk of breast cancer (additive model: OR =1.19, 95% CI: 1.02-1.38, P= 0.025). Further stratified analysis revealed that the SNP rs1205434 showed a significant difference for age at menarche strata (heterogeneity test P=0.009). Multiplicative interaction analysis indicated that there was positive multiplicative interaction between the SNP rs1205434 and menarche age (OR =1.09, 95% CI: 1.01-1.17, P=0.036). Additionally, expression quantitative trait loci analysis revealed that the SNP rs1205434 A allele could decrease the expression in the Genotype-Tissue Expression (GTEx) database (P=0.002). The Kaplan-Meier plotter showed that breast cancer patients with high expression have significantly better outcomes than those with low levels of expression (HR =0.84, 95% CI: 0.72-0.99, P=0.033).

CONCLUSIONS

The results indicate that the genetic variants (rs2306369 and rs1205434) in the coding region of and respectively may affect Chinese females' breast cancer susceptibility and act as potential predictive biomarkers for breast cancer.

摘要

背景

在Kazusa cDNA测序项目中鉴定出的KIAA基因可能在生物过程中发挥重要作用，并参与多种癌症的致癌过程。KIAA基因的遗传变异与这些基因的异常表达有关，并与几种人类复杂疾病的易感性相关。

方法

在乳腺癌的癌症基因组图谱（TCGA）数据库中筛选并鉴定差异表达的KIAA基因。选择位于28个KIAA基因中的48个变异，在1032例中国乳腺癌患者和1063例无癌对照中研究多态性与乳腺癌之间的关联。

结果

鉴定出两个编码变异，包括位于KIAA1462基因中的单核苷酸多态性（SNP）rs2306369和位于KIAA1522基因中的SNP rs1205434，它们与乳腺癌的发病率相关。逻辑回归分析显示，SNP rs2306369的G等位基因与乳腺癌风险降低相关（加性模型：比值比（OR）=0.81，95%置信区间（CI）：0.66-0.99，P=0.038），而SNP rs1205434的A等位基因与乳腺癌风险升高相关（加性模型：OR =1.19，95% CI：1.02-1.……

（原文此处95% CI区间不完整，翻译时保留原文格式）

……3%，P=0.025）。进一步的分层分析显示，SNP rs1205434在初潮年龄分层中存在显著差异（异质性检验P=0.009）。相乘交互作用分析表明，SNP rs1205434与初潮年龄之间存在正相乘交互作用（OR =1.09，95% CI：1.01-1.17，P=0.036）。此外，表达数量性状位点分析显示，SNP rs1205434的A等位基因可降低基因型-组织表达（GTEx）数据库中KIAA1522基因的表达（P=0.002）。Kaplan-Meier绘图仪显示，KIAA1522基因高表达的乳腺癌患者的预后明显优于低表达患者（风险比（HR）=0.84，95% CI：0.72-0.99，P=0.033）。