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

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

doi:10.21037/atm-20-6108

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

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

Authors

Jing Zhou^{1

2}, Congcong Chen^{1

3}, Sijun Liu⁴, Wen Zhou^{1

3}, Jiangbo Du^{1

5}, Yue Jiang^{1

5}, Juncheng Dai^{1

3

5}, Guangfu Jin^{1

3

5}, Hongxia Ma^{1

3

5}, Zhibin Hu^{1

3

5}, Jiaping Chen^{1

3}, Hongbing Shen^{1

3

5}

Affiliations

¹ 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.
² Statistical Center, Information Department, Northern Jiangsu People's Hospital and Clinical Medical College of Yangzhou University, Yangzhou, China.
³ Jiangsu Key Lab of Cancer Biomarkers, Prevention and Treatment, Collaborative Innovation Center for Cancer Medicine, Nanjing Medical University, Nanjing, China.
⁴ Department of Social Medicine and Health Education, School of Public Health, Nanjing Medical University, Nanjing, China.
⁵ State Key Laboratory of Reproductive Medicine, Nanjing Medical University, Nanjing, China.

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 KIAA1109 and a SNP rs1205434 in KIAA1755, 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 KIAA1755 expression in the Genotype-Tissue Expression (GTEx) database (P=0.002). The Kaplan-Meier plotter showed that breast cancer patients with high KIAA1755 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 KIAA1109 and KIAA1755 respectively may affect Chinese females' breast cancer susceptibility and act as potential predictive biomarkers for breast cancer.

Keywords: KIAA; breast cancer; genetic variants; susceptibility.