Association of selenoprotein and selenium pathway genotypes with risk of colorectal cancer and interaction with selenium status

Veronika Fedirko; Mazda Jenab; Catherine Méplan; Jeb S. Jones; Wanzhe Zhu; Lutz Schomburg; Afshan Siddiq; Sandra Hybsier; Kim Overvad; Anne Tjønneland; Hanane Omichessan; Vittorio Perduca; Marie Christine Boutron-Ruault; Tilman Kühn; Verena Katzke; Krasimira Aleksandrova; Antonia Trichopoulou; Anna Karakatsani; Anastasia Kotanidou; Rosario Tumino; Salvatore Panico; Giovanna Masala; Claudia Agnoli; Alessio Naccarati; Bas Bueno-De-Mesquita; Roel C.H. Vermeulen; Elisabete Weiderpass; Guri Skeie; Therese Haugdahl Nøst; Leila Lujan-Barroso; J. Ramón Quirós; José María Huerta; Miguel Rodríguez-Barranco; Aurelio Barricarte; Björn Gylling; Sophia Harlid; Kathryn E. Bradbury; Nick Wareham; Kay Tee Khaw; Marc Gunter; Neil Murphy; Heinz Freisling; Kostas Tsilidis; Dagfinn Aune; Elio Riboli; John E. Hesketh; David J. Hughes

doi:10.3390/NU11040935

Association of selenoprotein and selenium pathway genotypes with risk of colorectal cancer and interaction with selenium status

Veronika Fedirko, Mazda Jenab, Catherine Méplan, Jeb S. Jones, Wanzhe Zhu, Lutz Schomburg, Afshan Siddiq, Sandra Hybsier, Kim Overvad, Anne Tjønneland, Hanane Omichessan, Vittorio Perduca, Marie Christine Boutron-Ruault, Tilman Kühn, Verena Katzke, Krasimira Aleksandrova, Antonia Trichopoulou, Anna Karakatsani, Anastasia Kotanidou, Rosario TuminoSalvatore Panico, Giovanna Masala, Claudia Agnoli, Alessio Naccarati, Bas Bueno-De-Mesquita, Roel C.H. Vermeulen, Elisabete Weiderpass, Guri Skeie, Therese Haugdahl Nøst, Leila Lujan-Barroso, J. Ramón Quirós, José María Huerta, Miguel Rodríguez-Barranco, Aurelio Barricarte, Björn Gylling, Sophia Harlid, Kathryn E. Bradbury, Nick Wareham, Kay Tee Khaw, Marc Gunter, Neil Murphy, Heinz Freisling, Kostas Tsilidis, Dagfinn Aune, Elio Riboli, John E. Hesketh, David J. Hughes

Research output: Contribution to journal › Article › peer-review

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Abstract

Abstract: Selenoprotein genetic variations and suboptimal selenium (Se) levels may contribute to the risk of colorectal cancer (CRC) development. We examined the association between CRC risk and genotype for single nucleotide polymorphisms (SNPs) in selenoprotein and Se metabolic pathway genes. Illumina Goldengate assays were designed and resulted in the genotyping of 1040 variants in 154 genes from 1420 cases and 1421 controls within the European Prospective Investigation into Cancer and Nutrition (EPIC) study. Multivariable logistic regression revealed an association of 144 individual SNPs from 63 Se pathway genes with CRC risk. However, regarding the selenoprotein genes, only TXNRD1 rs11111979 retained borderline statistical significance after adjustment for correlated tests (P_ACT = 0.10; P_ACT significance threshold was P < 0.1). SNPs in Wingless/Integrated (Wnt) and Transforming growth factor (TGF) beta-signaling genes (FRZB, SMAD3, SMAD7) from pathways affected by Se intake were also associated with CRC risk after multiple testing adjustments. Interactions with Se status (using existing serum Se and Selenoprotein P data) were tested at the SNP, gene, and pathway levels. Pathway analyses using the modified Adaptive Rank Truncated Product method suggested that genes and gene x Se status interactions in antioxidant, apoptosis, and TGF-beta signaling pathways may be associated with CRC risk. This study suggests that SNPs in the Se pathway alone or in combination with suboptimal Se status may contribute to CRC development.

Original language	English (US)
Article number	935
Journal	Nutrients
Volume	11
Issue number	4
DOIs	https://doi.org/10.3390/NU11040935
State	Published - Apr 2019

Keywords

Biomarkers
Colorectal cancer risk
Colorectal neoplasms
Genetic epidemiology
Prospective cohort
Selenium
Selenium pathway
Selenium status
Selenoprotein P
Selenoprotein gene variation

ASJC Scopus subject areas

Food Science
Nutrition and Dietetics

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10.3390/NU11040935

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Fedirko, V., Jenab, M., Méplan, C., Jones, J. S., Zhu, W., Schomburg, L., Siddiq, A., Hybsier, S., Overvad, K., Tjønneland, A., Omichessan, H., Perduca, V., Boutron-Ruault, M. C., Kühn, T., Katzke, V., Aleksandrova, K., Trichopoulou, A., Karakatsani, A., Kotanidou, A., ... Hughes, D. J. (2019). Association of selenoprotein and selenium pathway genotypes with risk of colorectal cancer and interaction with selenium status. Nutrients, 11(4), Article 935. https://doi.org/10.3390/NU11040935

Fedirko, V, Jenab, M, Méplan, C, Jones, JS, Zhu, W, Schomburg, L, Siddiq, A, Hybsier, S, Overvad, K, Tjønneland, A, Omichessan, H, Perduca, V, Boutron-Ruault, MC, Kühn, T, Katzke, V, Aleksandrova, K, Trichopoulou, A, Karakatsani, A, Kotanidou, A, Tumino, R, Panico, S, Masala, G, Agnoli, C, Naccarati, A, Bueno-De-Mesquita, B, Vermeulen, RCH, Weiderpass, E, Skeie, G, Nøst, TH, Lujan-Barroso, L, Quirós, JR, Huerta, JM, Rodríguez-Barranco, M, Barricarte, A, Gylling, B, Harlid, S, Bradbury, KE, Wareham, N, Khaw, KT, Gunter, M, Murphy, N, Freisling, H, Tsilidis, K, Aune, D, Riboli, E, Hesketh, JE & Hughes, DJ 2019, 'Association of selenoprotein and selenium pathway genotypes with risk of colorectal cancer and interaction with selenium status', Nutrients, vol. 11, no. 4, 935. https://doi.org/10.3390/NU11040935

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title = "Association of selenoprotein and selenium pathway genotypes with risk of colorectal cancer and interaction with selenium status",

abstract = "Abstract: Selenoprotein genetic variations and suboptimal selenium (Se) levels may contribute to the risk of colorectal cancer (CRC) development. We examined the association between CRC risk and genotype for single nucleotide polymorphisms (SNPs) in selenoprotein and Se metabolic pathway genes. Illumina Goldengate assays were designed and resulted in the genotyping of 1040 variants in 154 genes from 1420 cases and 1421 controls within the European Prospective Investigation into Cancer and Nutrition (EPIC) study. Multivariable logistic regression revealed an association of 144 individual SNPs from 63 Se pathway genes with CRC risk. However, regarding the selenoprotein genes, only TXNRD1 rs11111979 retained borderline statistical significance after adjustment for correlated tests (PACT = 0.10; PACT significance threshold was P < 0.1). SNPs in Wingless/Integrated (Wnt) and Transforming growth factor (TGF) beta-signaling genes (FRZB, SMAD3, SMAD7) from pathways affected by Se intake were also associated with CRC risk after multiple testing adjustments. Interactions with Se status (using existing serum Se and Selenoprotein P data) were tested at the SNP, gene, and pathway levels. Pathway analyses using the modified Adaptive Rank Truncated Product method suggested that genes and gene x Se status interactions in antioxidant, apoptosis, and TGF-beta signaling pathways may be associated with CRC risk. This study suggests that SNPs in the Se pathway alone or in combination with suboptimal Se status may contribute to CRC development.",

keywords = "Biomarkers, Colorectal cancer risk, Colorectal neoplasms, Genetic epidemiology, Prospective cohort, Selenium, Selenium pathway, Selenium status, Selenoprotein P, Selenoprotein gene variation",

author = "Veronika Fedirko and Mazda Jenab and Catherine M{\'e}plan and Jones, {Jeb S.} and Wanzhe Zhu and Lutz Schomburg and Afshan Siddiq and Sandra Hybsier and Kim Overvad and Anne Tj{\o}nneland and Hanane Omichessan and Vittorio Perduca and Boutron-Ruault, {Marie Christine} and Tilman K{\"u}hn and Verena Katzke and Krasimira Aleksandrova and Antonia Trichopoulou and Anna Karakatsani and Anastasia Kotanidou and Rosario Tumino and Salvatore Panico and Giovanna Masala and Claudia Agnoli and Alessio Naccarati and Bas Bueno-De-Mesquita and Vermeulen, {Roel C.H.} and Elisabete Weiderpass and Guri Skeie and N{\o}st, {Therese Haugdahl} and Leila Lujan-Barroso and Quir{\'o}s, {J. Ram{\'o}n} and Huerta, {Jos{\'e} Mar{\'i}a} and Miguel Rodr{\'i}guez-Barranco and Aurelio Barricarte and Bj{\"o}rn Gylling and Sophia Harlid and Bradbury, {Kathryn E.} and Nick Wareham and Khaw, {Kay Tee} and Marc Gunter and Neil Murphy and Heinz Freisling and Kostas Tsilidis and Dagfinn Aune and Elio Riboli and Hesketh, {John E.} and Hughes, {David J.}",

note = "Publisher Copyright: {\textcopyright} 2019 by the authors. Licensee MDPI, Basel, Switzerland.",

year = "2019",

month = apr,

doi = "10.3390/NU11040935",

language = "English (US)",

volume = "11",

journal = "Nutrients",

issn = "2072-6643",

publisher = "Multidisciplinary Digital Publishing Institute (MDPI)",

number = "4",

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TY - JOUR

T1 - Association of selenoprotein and selenium pathway genotypes with risk of colorectal cancer and interaction with selenium status

AU - Fedirko, Veronika

AU - Jenab, Mazda

AU - Méplan, Catherine

AU - Jones, Jeb S.

AU - Zhu, Wanzhe

AU - Schomburg, Lutz

AU - Siddiq, Afshan

AU - Hybsier, Sandra

AU - Overvad, Kim

AU - Tjønneland, Anne

AU - Omichessan, Hanane

AU - Perduca, Vittorio

AU - Boutron-Ruault, Marie Christine

AU - Kühn, Tilman

AU - Katzke, Verena

AU - Aleksandrova, Krasimira

AU - Trichopoulou, Antonia

AU - Karakatsani, Anna

AU - Kotanidou, Anastasia

AU - Tumino, Rosario

AU - Panico, Salvatore

AU - Masala, Giovanna

AU - Agnoli, Claudia

AU - Naccarati, Alessio

AU - Bueno-De-Mesquita, Bas

AU - Vermeulen, Roel C.H.

AU - Weiderpass, Elisabete

AU - Skeie, Guri

AU - Nøst, Therese Haugdahl

AU - Lujan-Barroso, Leila

AU - Quirós, J. Ramón

AU - Huerta, José María

AU - Rodríguez-Barranco, Miguel

AU - Barricarte, Aurelio

AU - Gylling, Björn

AU - Harlid, Sophia

AU - Bradbury, Kathryn E.

AU - Wareham, Nick

AU - Khaw, Kay Tee

AU - Gunter, Marc

AU - Murphy, Neil

AU - Freisling, Heinz

AU - Tsilidis, Kostas

AU - Aune, Dagfinn

AU - Riboli, Elio

AU - Hesketh, John E.

AU - Hughes, David J.

PY - 2019/4

Y1 - 2019/4

N2 - Abstract: Selenoprotein genetic variations and suboptimal selenium (Se) levels may contribute to the risk of colorectal cancer (CRC) development. We examined the association between CRC risk and genotype for single nucleotide polymorphisms (SNPs) in selenoprotein and Se metabolic pathway genes. Illumina Goldengate assays were designed and resulted in the genotyping of 1040 variants in 154 genes from 1420 cases and 1421 controls within the European Prospective Investigation into Cancer and Nutrition (EPIC) study. Multivariable logistic regression revealed an association of 144 individual SNPs from 63 Se pathway genes with CRC risk. However, regarding the selenoprotein genes, only TXNRD1 rs11111979 retained borderline statistical significance after adjustment for correlated tests (PACT = 0.10; PACT significance threshold was P < 0.1). SNPs in Wingless/Integrated (Wnt) and Transforming growth factor (TGF) beta-signaling genes (FRZB, SMAD3, SMAD7) from pathways affected by Se intake were also associated with CRC risk after multiple testing adjustments. Interactions with Se status (using existing serum Se and Selenoprotein P data) were tested at the SNP, gene, and pathway levels. Pathway analyses using the modified Adaptive Rank Truncated Product method suggested that genes and gene x Se status interactions in antioxidant, apoptosis, and TGF-beta signaling pathways may be associated with CRC risk. This study suggests that SNPs in the Se pathway alone or in combination with suboptimal Se status may contribute to CRC development.

AB - Abstract: Selenoprotein genetic variations and suboptimal selenium (Se) levels may contribute to the risk of colorectal cancer (CRC) development. We examined the association between CRC risk and genotype for single nucleotide polymorphisms (SNPs) in selenoprotein and Se metabolic pathway genes. Illumina Goldengate assays were designed and resulted in the genotyping of 1040 variants in 154 genes from 1420 cases and 1421 controls within the European Prospective Investigation into Cancer and Nutrition (EPIC) study. Multivariable logistic regression revealed an association of 144 individual SNPs from 63 Se pathway genes with CRC risk. However, regarding the selenoprotein genes, only TXNRD1 rs11111979 retained borderline statistical significance after adjustment for correlated tests (PACT = 0.10; PACT significance threshold was P < 0.1). SNPs in Wingless/Integrated (Wnt) and Transforming growth factor (TGF) beta-signaling genes (FRZB, SMAD3, SMAD7) from pathways affected by Se intake were also associated with CRC risk after multiple testing adjustments. Interactions with Se status (using existing serum Se and Selenoprotein P data) were tested at the SNP, gene, and pathway levels. Pathway analyses using the modified Adaptive Rank Truncated Product method suggested that genes and gene x Se status interactions in antioxidant, apoptosis, and TGF-beta signaling pathways may be associated with CRC risk. This study suggests that SNPs in the Se pathway alone or in combination with suboptimal Se status may contribute to CRC development.

KW - Biomarkers

KW - Colorectal cancer risk

KW - Colorectal neoplasms

KW - Genetic epidemiology

KW - Prospective cohort

KW - Selenium

KW - Selenium pathway

KW - Selenium status

KW - Selenoprotein P

KW - Selenoprotein gene variation

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U2 - 10.3390/NU11040935

DO - 10.3390/NU11040935

M3 - Article

C2 - 31027226

AN - SCOPUS:85065294668

SN - 2072-6643

VL - 11

JO - Nutrients

JF - Nutrients

IS - 4

M1 - 935

ER -

Association of selenoprotein and selenium pathway genotypes with risk of colorectal cancer and interaction with selenium status

Abstract

Keywords

ASJC Scopus subject areas

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