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Vitamin D-Related Genes, Blood Vitamin D Levels and Colorectal Cancer Risk in Western European Populations

Higher circulating 25-hydroxyvitamin D levels (25(OH)D) have been found to be associated with lower risk for colorectal cancer (CRC) in prospective studies. Whether this association is modified by genetic variation in genes related to vitamin D metabolism and action has not been well studied in huma...

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Autores principales: Fedirko, Veronika, Mandle, Hannah B., Zhu, Wanzhe, Hughes, David J., Siddiq, Afshan, Ferrari, Pietro, Romieu, Isabelle, Riboli, Elio, Bueno-de-Mesquita, Bas, van Duijnhoven, Fränzel J.B., Siersema, Peter D., Tjønneland, Anne, Olsen, Anja, Perduca, Vittorio, Carbonnel, Franck, Boutron-Ruault, Marie-Christine, Kühn, Tilman, Johnson, Theron, Krasimira, Aleksandrova, Trichopoulou, Antonia, Makrythanasis, Periklis, Thanos, Dimitris, Panico, Salvatore, Krogh, Vittorio, Sacerdote, Carlotta, Skeie, Guri, Weiderpass, Elisabete, Colorado-Yohar, Sandra, Sala, Núria, Barricarte, Aurelio, Sanchez, Maria-Jose, Quirós, Ramón, Amiano, Pilar, Gylling, Björn, Harlid, Sophia, Perez-Cornago, Aurora, Heath, Alicia K., Tsilidis, Konstantinos K., Aune, Dagfinn, Freisling, Heinz, Murphy, Neil, Gunter, Marc J., Jenab, Mazda
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6722852/
https://www.ncbi.nlm.nih.gov/pubmed/31434255
http://dx.doi.org/10.3390/nu11081954
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author Fedirko, Veronika
Mandle, Hannah B.
Zhu, Wanzhe
Hughes, David J.
Siddiq, Afshan
Ferrari, Pietro
Romieu, Isabelle
Riboli, Elio
Bueno-de-Mesquita, Bas
van Duijnhoven, Fränzel J.B.
Siersema, Peter D.
Tjønneland, Anne
Olsen, Anja
Perduca, Vittorio
Carbonnel, Franck
Boutron-Ruault, Marie-Christine
Kühn, Tilman
Johnson, Theron
Krasimira, Aleksandrova
Trichopoulou, Antonia
Makrythanasis, Periklis
Thanos, Dimitris
Panico, Salvatore
Krogh, Vittorio
Sacerdote, Carlotta
Skeie, Guri
Weiderpass, Elisabete
Colorado-Yohar, Sandra
Sala, Núria
Barricarte, Aurelio
Sanchez, Maria-Jose
Quirós, Ramón
Amiano, Pilar
Gylling, Björn
Harlid, Sophia
Perez-Cornago, Aurora
Heath, Alicia K.
Tsilidis, Konstantinos K.
Aune, Dagfinn
Freisling, Heinz
Murphy, Neil
Gunter, Marc J.
Jenab, Mazda
author_facet Fedirko, Veronika
Mandle, Hannah B.
Zhu, Wanzhe
Hughes, David J.
Siddiq, Afshan
Ferrari, Pietro
Romieu, Isabelle
Riboli, Elio
Bueno-de-Mesquita, Bas
van Duijnhoven, Fränzel J.B.
Siersema, Peter D.
Tjønneland, Anne
Olsen, Anja
Perduca, Vittorio
Carbonnel, Franck
Boutron-Ruault, Marie-Christine
Kühn, Tilman
Johnson, Theron
Krasimira, Aleksandrova
Trichopoulou, Antonia
Makrythanasis, Periklis
Thanos, Dimitris
Panico, Salvatore
Krogh, Vittorio
Sacerdote, Carlotta
Skeie, Guri
Weiderpass, Elisabete
Colorado-Yohar, Sandra
Sala, Núria
Barricarte, Aurelio
Sanchez, Maria-Jose
Quirós, Ramón
Amiano, Pilar
Gylling, Björn
Harlid, Sophia
Perez-Cornago, Aurora
Heath, Alicia K.
Tsilidis, Konstantinos K.
Aune, Dagfinn
Freisling, Heinz
Murphy, Neil
Gunter, Marc J.
Jenab, Mazda
author_sort Fedirko, Veronika
collection PubMed
description Higher circulating 25-hydroxyvitamin D levels (25(OH)D) have been found to be associated with lower risk for colorectal cancer (CRC) in prospective studies. Whether this association is modified by genetic variation in genes related to vitamin D metabolism and action has not been well studied in humans. We investigated 1307 functional and tagging single-nucleotide polymorphisms (SNPs; individually, and by gene/pathway) in 86 vitamin D-related genes in 1420 incident CRC cases matched to controls from the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. We also evaluated the association between these SNPs and circulating 25(OH)D in a subset of controls. We confirmed previously reported CRC risk associations between SNPs in the VDR, GC, and CYP27B1 genes. We also identified additional associations with 25(OH)D, as well as CRC risk, and several potentially novel SNPs in genes related to vitamin D transport and action (LRP2, CUBN, NCOA7, and HDAC9). However, none of these SNPs were statistically significant after Benjamini–Hochberg (BH) multiple testing correction. When assessed by a priori defined functional pathways, tumor growth factor β (TGFβ) signaling was associated with CRC risk (P ≤ 0.001), with most statistically significant genes being SMAD7 (P(BH) = 0.008) and SMAD3 (P(BH) = 0.008), and 18 SNPs in the vitamin D receptor (VDR) binding sites (P = 0.036). The 25(OH)D-gene pathway analysis suggested that genetic variants in the genes related to VDR complex formation and transcriptional activity are associated with CRC depending on 25(OH)D levels (interaction P = 0.041). Additional studies in large populations and consortia, especially with measured circulating 25(OH)D, are needed to confirm our findings.
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spelling pubmed-67228522019-09-10 Vitamin D-Related Genes, Blood Vitamin D Levels and Colorectal Cancer Risk in Western European Populations Fedirko, Veronika Mandle, Hannah B. Zhu, Wanzhe Hughes, David J. Siddiq, Afshan Ferrari, Pietro Romieu, Isabelle Riboli, Elio Bueno-de-Mesquita, Bas van Duijnhoven, Fränzel J.B. Siersema, Peter D. Tjønneland, Anne Olsen, Anja Perduca, Vittorio Carbonnel, Franck Boutron-Ruault, Marie-Christine Kühn, Tilman Johnson, Theron Krasimira, Aleksandrova Trichopoulou, Antonia Makrythanasis, Periklis Thanos, Dimitris Panico, Salvatore Krogh, Vittorio Sacerdote, Carlotta Skeie, Guri Weiderpass, Elisabete Colorado-Yohar, Sandra Sala, Núria Barricarte, Aurelio Sanchez, Maria-Jose Quirós, Ramón Amiano, Pilar Gylling, Björn Harlid, Sophia Perez-Cornago, Aurora Heath, Alicia K. Tsilidis, Konstantinos K. Aune, Dagfinn Freisling, Heinz Murphy, Neil Gunter, Marc J. Jenab, Mazda Nutrients Article Higher circulating 25-hydroxyvitamin D levels (25(OH)D) have been found to be associated with lower risk for colorectal cancer (CRC) in prospective studies. Whether this association is modified by genetic variation in genes related to vitamin D metabolism and action has not been well studied in humans. We investigated 1307 functional and tagging single-nucleotide polymorphisms (SNPs; individually, and by gene/pathway) in 86 vitamin D-related genes in 1420 incident CRC cases matched to controls from the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. We also evaluated the association between these SNPs and circulating 25(OH)D in a subset of controls. We confirmed previously reported CRC risk associations between SNPs in the VDR, GC, and CYP27B1 genes. We also identified additional associations with 25(OH)D, as well as CRC risk, and several potentially novel SNPs in genes related to vitamin D transport and action (LRP2, CUBN, NCOA7, and HDAC9). However, none of these SNPs were statistically significant after Benjamini–Hochberg (BH) multiple testing correction. When assessed by a priori defined functional pathways, tumor growth factor β (TGFβ) signaling was associated with CRC risk (P ≤ 0.001), with most statistically significant genes being SMAD7 (P(BH) = 0.008) and SMAD3 (P(BH) = 0.008), and 18 SNPs in the vitamin D receptor (VDR) binding sites (P = 0.036). The 25(OH)D-gene pathway analysis suggested that genetic variants in the genes related to VDR complex formation and transcriptional activity are associated with CRC depending on 25(OH)D levels (interaction P = 0.041). Additional studies in large populations and consortia, especially with measured circulating 25(OH)D, are needed to confirm our findings. MDPI 2019-08-20 /pmc/articles/PMC6722852/ /pubmed/31434255 http://dx.doi.org/10.3390/nu11081954 Text en © 2019 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Fedirko, Veronika
Mandle, Hannah B.
Zhu, Wanzhe
Hughes, David J.
Siddiq, Afshan
Ferrari, Pietro
Romieu, Isabelle
Riboli, Elio
Bueno-de-Mesquita, Bas
van Duijnhoven, Fränzel J.B.
Siersema, Peter D.
Tjønneland, Anne
Olsen, Anja
Perduca, Vittorio
Carbonnel, Franck
Boutron-Ruault, Marie-Christine
Kühn, Tilman
Johnson, Theron
Krasimira, Aleksandrova
Trichopoulou, Antonia
Makrythanasis, Periklis
Thanos, Dimitris
Panico, Salvatore
Krogh, Vittorio
Sacerdote, Carlotta
Skeie, Guri
Weiderpass, Elisabete
Colorado-Yohar, Sandra
Sala, Núria
Barricarte, Aurelio
Sanchez, Maria-Jose
Quirós, Ramón
Amiano, Pilar
Gylling, Björn
Harlid, Sophia
Perez-Cornago, Aurora
Heath, Alicia K.
Tsilidis, Konstantinos K.
Aune, Dagfinn
Freisling, Heinz
Murphy, Neil
Gunter, Marc J.
Jenab, Mazda
Vitamin D-Related Genes, Blood Vitamin D Levels and Colorectal Cancer Risk in Western European Populations
title Vitamin D-Related Genes, Blood Vitamin D Levels and Colorectal Cancer Risk in Western European Populations
title_full Vitamin D-Related Genes, Blood Vitamin D Levels and Colorectal Cancer Risk in Western European Populations
title_fullStr Vitamin D-Related Genes, Blood Vitamin D Levels and Colorectal Cancer Risk in Western European Populations
title_full_unstemmed Vitamin D-Related Genes, Blood Vitamin D Levels and Colorectal Cancer Risk in Western European Populations
title_short Vitamin D-Related Genes, Blood Vitamin D Levels and Colorectal Cancer Risk in Western European Populations
title_sort vitamin d-related genes, blood vitamin d levels and colorectal cancer risk in western european populations
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6722852/
https://www.ncbi.nlm.nih.gov/pubmed/31434255
http://dx.doi.org/10.3390/nu11081954
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