KLK3 Snp–snp Interactions for Prediction of Prostate Cancer Aggressiveness

Authors

Hui Yi Lin, LSU Health Sciences Center- New OrleansFollow
Po Yu Huang, Industrial Technology Research Institute of Taiwan
Chia Ho Cheng, Moffitt Cancer Center
Heng Yuan Tung, LSU Health Sciences Center- New Orleans
Zhide Fang, LSU Health Sciences Center- New OrleansFollow
Anders E. Berglund, Moffitt Cancer Center
Ann Chen, Moffitt Cancer Center
Jennifer French-Kwawu, LSU Health Sciences Center- New Orleans
Darian Harris, LSU Health Sciences Center- New Orleans
Julio Pow-Sang, Moffitt Cancer Center
Kosj Yamoah, Moffitt Cancer Center
John L. Cleveland, Moffitt Cancer Center
Shivanshu Awasthi, Moffitt Cancer Center
Robert J. Rounbehler, Moffitt Cancer Center
Travis Gerke, Moffitt Cancer Center
Jasreman Dhillon, Moffitt Cancer Center
Rosalind Eeles, The Institute of Cancer Research
Rosalind Eeles, The Institute of Cancer Research
Zsofia Kote-Jarai, The Institute of Cancer Research
Zsofia Kote-Jarai, The Institute of Cancer Research

Document Type

Article

Publication Date

4-29-2021

Publication Title

Scientific Reports

Abstract

Risk classification for prostate cancer (PCa) aggressiveness and underlying mechanisms remain inadequate. Interactions between single nucleotide polymorphisms (SNPs) may provide a solution to fill these gaps. To identify SNP–SNP interactions in the four pathways (the angiogenesis-, mitochondria-, miRNA-, and androgen metabolism-related pathways) associated with PCa aggressiveness, we tested 8587 SNPs for 20,729 cases from the PCa consortium. We identified 3 KLK3 SNPs, and 1083 (P < 3.5 × 10–9) and 3145 (P < 1 × 10–5) SNP–SNP interaction pairs significantly associated with PCa aggressiveness. These SNP pairs associated with PCa aggressiveness were more significant than each of their constituent SNP individual effects. The majority (98.6%) of the 3145 pairs involved KLK3. The 3 most common gene–gene interactions were KLK3-COL4A1:COL4A2, KLK3-CDH13, and KLK3-TGFBR3. Predictions from the SNP interaction-based polygenic risk score based on 24 SNP pairs are promising. The prevalence of PCa aggressiveness was 49.8%, 21.9%, and 7.0% for the PCa cases from our cohort with the top 1%, middle 50%, and bottom 1% risk profiles. Potential biological functions of the identified KLK3 SNP–SNP interactions were supported by gene expression and protein–protein interaction results. Our findings suggest KLK3 SNP interactions may play an important role in PCa aggressiveness.

First Page

1

Last Page

15

PubMed ID

33927218

Volume

11

Issue

1

Publisher

Nature Research

Creative Commons License

This work is licensed under a Creative Commons Attribution 4.0 International License.

Recommended Citation

Lin, Hui Yi; Huang, Po Yu; Cheng, Chia Ho; Tung, Heng Yuan; Fang, Zhide; Berglund, Anders E.; Chen, Ann; French-Kwawu, Jennifer; Harris, Darian; Pow-Sang, Julio; Yamoah, Kosj; Cleveland, John L.; Awasthi, Shivanshu; Rounbehler, Robert J.; Gerke, Travis; Dhillon, Jasreman; Eeles, Rosalind; Eeles, Rosalind; Kote-Jarai, Zsofia; and Kote-Jarai, Zsofia, "KLK3 Snp–snp Interactions for Prediction of Prostate Cancer Aggressiveness" (2021). School of Public Health Faculty Publications. 26.
https://digitalscholar.lsuhsc.edu/soph_facpubs/26
10.1038/s41598-021-85169-7

File Format

pdf

File Size

1675 KB