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

V. Fedirko; M. Jenab; C. Méplan; W. Zhu; L. Schomburg; A. Siddiq; S. Hybsier; K. Overvad; A. Tjønneland; H. Omichessan; V. Perduca; M.-C. Boutron-Ruault; T. Kühn; V. Katzke; K. Aleksandrova; A. Trichopoulou; A. Karakatsani; A. Kotanidou; R. Tumino; S. Panico; G. Masala; C. Agnoli; A. Naccarati; B. Bueno-De-Mesquita; R.C.H. Vermeulen; E. Weiderpass; G. Skeie; T.H. Nøst; L. Lujan-Barroso; J.R. Quirós; J.M. Huerta; M. Rodríguez-Barranco; A. Barricarte; B. Gylling; S. Harlid; K.E. Bradbury; N. Wareham; K.-T. Khaw; M. Gunter; N. Murphy; H. Freisling; K. Tsilidis; D. Aune; E. Riboli; J.E. Hesketh; D.J. Hughes

doi:10.3390/NU11040935

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

V. Fedirko
, M. Jenab
, C. Méplan
, W. Zhu
, L. Schomburg
, A. Siddiq
, S. Hybsier
, K. Overvad
, A. Tjønneland
, H. Omichessan
, V. Perduca
, M.-C. Boutron-Ruault
, T. Kühn
, V. Katzke
, K. Aleksandrova
, A. Trichopoulou
, A. Karakatsani
, A. Kotanidou
, R. Tumino
, S. Panico

G. Masala, C. Agnoli, A. Naccarati, B. Bueno-De-Mesquita, R.C.H. Vermeulen, E. Weiderpass, G. Skeie, T.H. Nøst, L. Lujan-Barroso, J.R. Quirós, J.M. Huerta, M. Rodríguez-Barranco, A. Barricarte, B. Gylling, S. Harlid, K.E. Bradbury, N. Wareham, K.-T. Khaw, M. Gunter, N. Murphy, H. Freisling, K. Tsilidis, D. Aune, E. Riboli, J.E. Hesketh, D.J. Hughes^*

^*Corresponding author for this work

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

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.

Original language	English
Article number	935
Journal	Nutrients
Volume	11
Issue number	4
DOIs	https://doi.org/10.3390/NU11040935
Publication status	Published - 2019

Bibliographical note

Cited By :13

Export Date: 8 December 2021

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This output contributes to the following UN Sustainable Development Goals (SDGs)

SDG 3 Good Health and Well-being

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Fedirko, V., Jenab, M., Méplan, C., 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., Tumino, R., ... 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

@article{5f0f00c827be4cb099b15666ae25e974,

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

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.",

author = "V. Fedirko and M. Jenab and C. M{\'e}plan and W. Zhu and L. Schomburg and A. Siddiq and S. Hybsier and K. Overvad and A. Tj{\o}nneland and H. Omichessan and V. Perduca and M.-C. Boutron-Ruault and T. K{\"u}hn and V. Katzke and K. Aleksandrova and A. Trichopoulou and A. Karakatsani and A. Kotanidou and R. Tumino and S. Panico and G. Masala and C. Agnoli and A. Naccarati and B. Bueno-De-Mesquita and R.C.H. Vermeulen and E. Weiderpass and G. Skeie and T.H. N{\o}st and L. Lujan-Barroso and J.R. Quir{\'o}s and J.M. Huerta and M. Rodr{\'i}guez-Barranco and A. Barricarte and B. Gylling and S. Harlid and K.E. Bradbury and N. Wareham and K.-T. Khaw and M. Gunter and N. Murphy and H. Freisling and K. Tsilidis and D. Aune and E. Riboli and J.E. Hesketh and D.J. Hughes",

note = "Cited By :13 Export Date: 8 December 2021",

year = "2019",

doi = "10.3390/NU11040935",

language = "English",

volume = "11",

journal = "Nutrients",

issn = "2072-6643",

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

number = "4",

}

Fedirko, V, Jenab, M, Méplan, C, 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, 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, K-T, 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

TY - JOUR

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

AU - Fedirko, V.

AU - Jenab, M.

AU - Méplan, C.

AU - Zhu, W.

AU - Schomburg, L.

AU - Siddiq, A.

AU - Hybsier, S.

AU - Overvad, K.

AU - Tjønneland, A.

AU - Omichessan, H.

AU - Perduca, V.

AU - Boutron-Ruault, M.-C.

AU - Kühn, T.

AU - Katzke, V.

AU - Aleksandrova, K.

AU - Trichopoulou, A.

AU - Karakatsani, A.

AU - Kotanidou, A.

AU - Tumino, R.

AU - Panico, S.

AU - Masala, G.

AU - Agnoli, C.

AU - Naccarati, A.

AU - Bueno-De-Mesquita, B.

AU - Vermeulen, R.C.H.

AU - Weiderpass, E.

AU - Skeie, G.

AU - Nøst, T.H.

AU - Lujan-Barroso, L.

AU - Quirós, J.R.

AU - Huerta, J.M.

AU - Rodríguez-Barranco, M.

AU - Barricarte, A.

AU - Gylling, B.

AU - Harlid, S.

AU - Bradbury, K.E.

AU - Wareham, N.

AU - Khaw, K.-T.

AU - Gunter, M.

AU - Murphy, N.

AU - Freisling, H.

AU - Tsilidis, K.

AU - Aune, D.

AU - Riboli, E.

AU - Hesketh, J.E.

AU - Hughes, D.J.

N1 - Cited By :13 Export Date: 8 December 2021

PY - 2019

Y1 - 2019

N2 - 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 - 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.

U2 - 10.3390/NU11040935

DO - 10.3390/NU11040935

M3 - Article

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

Bibliographical note

UN SDGs

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