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

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...

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Bibliographic Details
Published in:NPJ breast cancer 2021-09, Vol.7 (1), p.118-118, Article 118
Main Authors: Fores-Martos, Jaume, Cervera-Vidal, Raimundo, Sierra-Roca, Julia, Lozano-Asencio, Carlos, Fedele, Vita, Cornelissen, Sten, Edvarsen, Hege, Tadeo-Cervera, Irene, Eroles, Pilar, Lluch, Ana, Tabares-Seisdedos, Rafa, Falcó, Antonio, Van’t Veer, Laura J., Schmidt, Marjanka, Quigley, David A., Børresen-Dale, Anne-Lise, Kristensen, Vessela N., Balmain, Allan, Climent, Joan
Format: Article
Language:English
Subjects:
631/208/205
692/4028/67/68
Biomedical and Life Sciences
Biomedicine
Breast cancer
Cancer Research
Cell Biology
Circadian rhythm
Genotype & phenotype
Human Genetics
Medical research
Meta-analysis
Mutation
Oncology
Polymorphism
Womens health
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Summary: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 PER3 VNRT 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.
ISSN:2374-4677
2374-4677
DOI:10.1038/s41523-021-00329-2