Circadian PERformance in breast cancer: a germline and somatic genetic study of PER3 VNTR 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...
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2021
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oai:doaj.org-article:4e917fb342074343a2b9ae2128ef604c2021-12-02T14:54:51ZCircadian PERformance in breast cancer: a germline and somatic genetic study of PER3 VNTR polymorphisms and gene co-expression10.1038/s41523-021-00329-22374-4677https://doaj.org/article/4e917fb342074343a2b9ae2128ef604c2021-09-01T00:00:00Zhttps://doi.org/10.1038/s41523-021-00329-2https://doaj.org/toc/2374-4677Abstract 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.Jaume Fores-MartosRaimundo Cervera-VidalJulia Sierra-RocaCarlos Lozano-AsencioVita FedeleSten CornelissenHege EdvarsenIrene Tadeo-CerveraPilar ErolesAna LluchRafa Tabares-SeisdedosAntonio FalcóLaura J. Van’t VeerMarjanka SchmidtDavid A. QuigleyAnne-Lise Børresen-DaleVessela N. KristensenAllan BalmainJoan ClimentNature PortfolioarticleNeoplasms. Tumors. Oncology. Including cancer and carcinogensRC254-282ENnpj Breast Cancer, Vol 7, Iss 1, Pp 1-12 (2021) |
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Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282 |
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Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282 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 Circadian PERformance in breast cancer: a germline and somatic genetic study of PER3 VNTR polymorphisms and gene co-expression |
| description |
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 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. |
| format |
article |
| author |
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 |
| author_facet |
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 |
| author_sort |
Jaume Fores-Martos |
| title |
Circadian PERformance in breast cancer: a germline and somatic genetic study of PER3 VNTR polymorphisms and gene co-expression |
| title_short |
Circadian PERformance in breast cancer: a germline and somatic genetic study of PER3 VNTR polymorphisms and gene co-expression |
| title_full |
Circadian PERformance in breast cancer: a germline and somatic genetic study of PER3 VNTR polymorphisms and gene co-expression |
| title_fullStr |
Circadian PERformance in breast cancer: a germline and somatic genetic study of PER3 VNTR polymorphisms and gene co-expression |
| title_full_unstemmed |
Circadian PERformance in breast cancer: a germline and somatic genetic study of PER3 VNTR polymorphisms and gene co-expression |
| title_sort |
circadian performance in breast cancer: a germline and somatic genetic study of per3 vntr polymorphisms and gene co-expression |
| publisher |
Nature Portfolio |
| publishDate |
2021 |
| url |
https://doaj.org/article/4e917fb342074343a2b9ae2128ef604c |
| work_keys_str_mv |
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