Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2021 Apr;9(7):549.
doi: 10.21037/atm-20-6108.

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

Jing Zhou  1   2 , Congcong Chen  1   3 , Sijun Liu  4 , 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

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

Jing Zhou et al. Ann Transl Med. 2021 Apr.

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.

PubMed Disclaimer

Conflict of interest statement

Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at http://dx.doi.org/10.21037/atm-20-6108). The authors declare that they have no conflict of interest regarding the publication of this paper.

Figures

Figure 1
Figure 1
Flow chart for selecting SNPs in the KIAA genes. MAF, minor allele frequency; LD, linkage disequilibrium; UTR, untranslated region; CHB, Han Chinese in Beijing, China.
Figure 2
Figure 2
eQTL analysis of the rs1205434 in breast mammary tissues with the Gene-Tissue Expression (GTEx) database. Boxplots showing the effects of the genotypes of rs1205434 on KIAA1755 expression levels (P=0.002).
Figure 3
Figure 3
Kaplan-Meier survival curve of breast cancer patients according to the mRNA expression level of KIAA1755 and KIAA1109. (A) The Kaplan Meier curve shows that breast cancer patients with high expression of KIAA1755 had significant better outcome than those with low expression (P=0.033); (B) the Kaplan Meier curve shows that the outcome of breast cancer patients had no significant differences between the high expression of KIAA1109 group and the low expression of KIAA1109 group
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

References

    1. Bray F, Ferlay J, Soerjomataram I, et al. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin 2018;68:394-424. 10.3322/caac.21492 - DOI - PubMed
    1. Baselga J, Norton L. Focus on breast cancer. Cancer Cell 2002;1:319-22. 10.1016/S1535-6108(02)00066-1 - DOI - PubMed
    1. Milne RL, Kuchenbaecker KB, Michailidou K, et al. Identification of ten variants associated with risk of estrogen-receptor-negative breast cancer. Nat Genet 2017;49:1767-78. 10.1038/ng.3785 - DOI - PMC - PubMed
    1. Michailidou K, Lindström S, Dennis J, et al. Association analysis identifies 65 new breast cancer risk loci. Nature 2017;551:92-4. 10.1038/nature24284 - DOI - PMC - PubMed
    1. Fachal L, Aschard H, Beesley J, et al. Fine-mapping of 150 breast cancer risk regions identifies 191 likely target genes. Nat Genet 2020;52:56-73. 10.1038/s41588-019-0537-1 - DOI - PMC - PubMed

LinkOut - more resources