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Circadian pathway genetic variation and cancer risk: evidence from genome-wide association studies
BACKGROUND: Dysfunction of the circadian clock and single polymorphisms of some circadian genes have been linked to cancer susceptibility, although data are scarce and findings inconsistent. We aimed to investigate the association between circadian pathway genetic variation and risk of developing co...
Autores principales: | , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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BioMed Central
2018
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5817863/ https://www.ncbi.nlm.nih.gov/pubmed/29455641 http://dx.doi.org/10.1186/s12916-018-1010-1 |
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author | Mocellin, Simone Tropea, Saveria Benna, Clara Rossi, Carlo Riccardo |
author_facet | Mocellin, Simone Tropea, Saveria Benna, Clara Rossi, Carlo Riccardo |
author_sort | Mocellin, Simone |
collection | PubMed |
description | BACKGROUND: Dysfunction of the circadian clock and single polymorphisms of some circadian genes have been linked to cancer susceptibility, although data are scarce and findings inconsistent. We aimed to investigate the association between circadian pathway genetic variation and risk of developing common cancers based on the findings of genome-wide association studies (GWASs). METHODS: Single nucleotide polymorphisms (SNPs) of 17 circadian genes reported by three GWAS meta-analyses dedicated to breast (Discovery, Biology, and Risk of Inherited Variants in Breast Cancer (DRIVE) Consortium; cases, n = 15,748; controls, n = 18,084), prostate (Elucidating Loci Involved in Prostate Cancer Susceptibility (ELLIPSE) Consortium; cases, n = 14,160; controls, n = 12,724) and lung carcinoma (Transdisciplinary Research In Cancer of the Lung (TRICL) Consortium; cases, n = 12,160; controls, n = 16,838) in patients of European ancestry were utilized to perform pathway analysis by means of the adaptive rank truncated product (ARTP) method. Data were also available for the following subgroups: estrogen receptor negative breast cancer, aggressive prostate cancer, squamous lung carcinoma and lung adenocarcinoma. RESULTS: We found a highly significant statistical association between circadian pathway genetic variation and the risk of breast (pathway P value = 1.9 × 10(–6); top gene RORA, gene P value = 0.0003), prostate (pathway P value = 4.1 × 10(–6); top gene ARNTL, gene P value = 0.0002) and lung cancer (pathway P value = 6.9 × 10(–7); top gene RORA, gene P value = 2.0 × 10(–6)), as well as all their subgroups. Out of 17 genes investigated, 15 were found to be significantly associated with the risk of cancer: four genes were shared by all three malignancies (ARNTL, CLOCK, RORA and RORB), two by breast and lung cancer (CRY1 and CRY2) and three by prostate and lung cancer (NPAS2, NR1D1 and PER3), whereas four genes were specific for lung cancer (ARNTL2, CSNK1E, NR1D2 and PER2) and two for breast cancer (PER1, RORC). CONCLUSIONS: Our findings, based on the largest series ever utilized for ARTP-based gene and pathway analysis, support the hypothesis that circadian pathway genetic variation is involved in cancer predisposition. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12916-018-1010-1) contains supplementary material, which is available to authorized users. |
format | Online Article Text |
id | pubmed-5817863 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-58178632018-02-23 Circadian pathway genetic variation and cancer risk: evidence from genome-wide association studies Mocellin, Simone Tropea, Saveria Benna, Clara Rossi, Carlo Riccardo BMC Med Research Article BACKGROUND: Dysfunction of the circadian clock and single polymorphisms of some circadian genes have been linked to cancer susceptibility, although data are scarce and findings inconsistent. We aimed to investigate the association between circadian pathway genetic variation and risk of developing common cancers based on the findings of genome-wide association studies (GWASs). METHODS: Single nucleotide polymorphisms (SNPs) of 17 circadian genes reported by three GWAS meta-analyses dedicated to breast (Discovery, Biology, and Risk of Inherited Variants in Breast Cancer (DRIVE) Consortium; cases, n = 15,748; controls, n = 18,084), prostate (Elucidating Loci Involved in Prostate Cancer Susceptibility (ELLIPSE) Consortium; cases, n = 14,160; controls, n = 12,724) and lung carcinoma (Transdisciplinary Research In Cancer of the Lung (TRICL) Consortium; cases, n = 12,160; controls, n = 16,838) in patients of European ancestry were utilized to perform pathway analysis by means of the adaptive rank truncated product (ARTP) method. Data were also available for the following subgroups: estrogen receptor negative breast cancer, aggressive prostate cancer, squamous lung carcinoma and lung adenocarcinoma. RESULTS: We found a highly significant statistical association between circadian pathway genetic variation and the risk of breast (pathway P value = 1.9 × 10(–6); top gene RORA, gene P value = 0.0003), prostate (pathway P value = 4.1 × 10(–6); top gene ARNTL, gene P value = 0.0002) and lung cancer (pathway P value = 6.9 × 10(–7); top gene RORA, gene P value = 2.0 × 10(–6)), as well as all their subgroups. Out of 17 genes investigated, 15 were found to be significantly associated with the risk of cancer: four genes were shared by all three malignancies (ARNTL, CLOCK, RORA and RORB), two by breast and lung cancer (CRY1 and CRY2) and three by prostate and lung cancer (NPAS2, NR1D1 and PER3), whereas four genes were specific for lung cancer (ARNTL2, CSNK1E, NR1D2 and PER2) and two for breast cancer (PER1, RORC). CONCLUSIONS: Our findings, based on the largest series ever utilized for ARTP-based gene and pathway analysis, support the hypothesis that circadian pathway genetic variation is involved in cancer predisposition. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12916-018-1010-1) contains supplementary material, which is available to authorized users. BioMed Central 2018-02-19 /pmc/articles/PMC5817863/ /pubmed/29455641 http://dx.doi.org/10.1186/s12916-018-1010-1 Text en © The Author(s). 2018 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated. |
spellingShingle | Research Article Mocellin, Simone Tropea, Saveria Benna, Clara Rossi, Carlo Riccardo Circadian pathway genetic variation and cancer risk: evidence from genome-wide association studies |
title | Circadian pathway genetic variation and cancer risk: evidence from genome-wide association studies |
title_full | Circadian pathway genetic variation and cancer risk: evidence from genome-wide association studies |
title_fullStr | Circadian pathway genetic variation and cancer risk: evidence from genome-wide association studies |
title_full_unstemmed | Circadian pathway genetic variation and cancer risk: evidence from genome-wide association studies |
title_short | Circadian pathway genetic variation and cancer risk: evidence from genome-wide association studies |
title_sort | circadian pathway genetic variation and cancer risk: evidence from genome-wide association studies |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5817863/ https://www.ncbi.nlm.nih.gov/pubmed/29455641 http://dx.doi.org/10.1186/s12916-018-1010-1 |
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