Circadian PERformance in breast cancer: a germline and somatic genetic study of PER3VNTR polymorphisms and gene co-expression.

Abstract

Polymorphisms in the PER3 gene have been associated with several human disease phenotypes, including sleep disorders and cancer. In particular, the long allele of a variable number of tandem repeat (VNTR) polymorphism has been previously linked to an increased risk of breast cancer. Here we carried out a combined germline and somatic genetic analysis of the role of the PER3VNRT polymorphism in breast cancer. The combined data from 8284 individuals showed a non-significant trend towards increased breast cancer risk in the 5-repeat allele homozygous carriers (OR = 1.17, 95% CI: 0.97-1.42). We observed allelic imbalance at the PER3 locus in matched blood and tumor DNA samples, showing a significant retention of the long variant (risk) allele in tumor samples, and a preferential loss of the short repetition allele (p = 0.0005). Gene co-expression analysis in healthy and tumoral breast tissue samples uncovered significant associations between PER3 expression levels with those from genes which belong to several cancer-associated pathways. Finally, relapse-free survival (RFS) analysis showed that low expression levels of PER3 were linked to a significant lower RSF in luminal A (p = 3 × 10-12) but not in the rest of breast cancer subtypes.

• Authors: Jaume Fores-Martos, Raimundo Cervera-Vidal, Julia Sierra-Roca, Carlos Lozano-Asencio, Vita Fedele, Sten Cornelissen, Hege Edvarsen, Irene Tadeo-Cervera, Pilar Eroles, Ana Lluch, Rafa Tabares-Seisdedos, Antonio Falcó, Laura J Van't Veer, Marjanka Schmidt, David A Quigley, Anne-Lise Børresen-Dale, Vessela N Kristensen, Allan Balmain, Joan Climent
• Journal: NPJ breast cancer (NPJ Breast Cancer) Vol. 7 Issue 1 Pg. 118 (Sep 10 2021) ISSN: 2374-4677 [Print] United States
• PMID: 34508103 (Publication Type: Journal Article)
• Copyright: © 2021. The Author(s).