Circadian PERformance in breast cancer: a germline and somatic genetic study of PER3VNTR polymorphisms and gene co-expression
Year: 2021
Type: article
Study design: Observational Study
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.
Source: npj Breast Cancer
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
Institutions: Universidad Cardenal Herrera CEU, Centro de Investigación Biomédica en Red de Salud Mental, Hospital Clínico Universitario de Valencia, INCLIVA Health Research Institute, Hospital Universitari i Politècnic La Fe, University of Verona, The Netherlands Cancer Institute, Oslo University Hospital, Universitat de València, University of California, San Francisco, UCSF Helen Diller Family Comprehensive Cancer Center
Language: English
Subfield: Endocrine and Autonomic Systems
Field: Neuroscience
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $3,170
Awards: G1075404386, G3912641898, Arquitectura genómica del cáncer de mama triple negativo. Análisis mediante genética de sistemas del riesgo a la progresión tumoral y respuesta terapéutica, De la genómica del cáncer a la inmuno-oncologia. Búsqueda de biomarcadores de respuesta a la inmunoterapia anti-PD1/PDL1 en cáncer mediante una aproximación de biología de sistemas, G8326292490, Systems genetics analysis of tumor evolution in the mouse
OpenAlex ID: W3197041067