Association of Selenoprotein and Selenium Pathway Genotypes with Risk of Colorectal Cancer and Interaction with Selenium Status

被引：23

作者：

Fedirko, Veronika ^{[1
,2
]}

Jenab, Mazda ^{[3
]}

Meplan, Catherine ^{[4
]}

Jones, Jeb S. ^{[1
,2
]}

Zhu, Wanzhe ^{[1
,2
]}

Schomburg, Lutz ^{[5
]}

Siddiq, Afshan ^{[6
]}

Hybsier, Sandra ^{[5
]}

Overvad, Kim ^{[7
]}

Tjonneland, Anne ^{[8
]}

Omichessan, Hanane ^{[9
,10
]}

Perduca, Vittorio ^{[9
,10
,11
]}

Boutron-Ruault, Marie-Christine ^{[9
,10
]}

Kuehn, Tilman ^{[12
]}

Katzke, Verena ^{[12
]}

Aleksandrova, Krasimira ^{[13
]}

Trichopoulou, Antonia ^{[14
]}

Karakatsani, Anna ^{[14
,15
]}

Kotanidou, Anastasia ^{[14
,16
]}

Tumino, Rosario ^{[17
,18
]}

Panico, Salvatore ^{[19
]}

Masala, Giovanna ^{[20
]}

Agnoli, Claudia ^{[21
]}

Naccarati, Alessio ^{[22
]}

Bueno-de-Mesquita, Bas ^{[6
,23
,24
,25
]}

Vermeulen, Roel C. H. ^{[26
]}

Weiderpass, Elisabete ^{[27
,28
,29
,30
,31
]}

Skeie, Guri ^{[31
]}

Nost, Therese Haugdahl ^{[31
]}

Lujan-Barroso, Leila ^{[32
]}

Ramon Quiros, J. ^{[33
]}

Maria Huerta, Jose ^{[34
,35
]}

Rodriguez-Barranco, Miguel ^{[35
,36
]}

Barricarte, Aurelio ^{[35
,37
,38
]}

Gylling, Bjoern ^{[39
]}

Harlid, Sophia ^{[40
]}

Bradbury, Kathryn E. ^{[41
]}

Wareham, Nick ^{[42
]}

Khaw, Kay-Tee ^{[43
]}

Gunter, Marc ^{[3
]}

Murphy, Neil ^{[3
]}

Freisling, Heinz ^{[3
]}

Tsilidis, Kostas ^{[6
,44
]}

Aune, Dagfinn ^{[6
,45
,46
]}

Riboli, Elio ^{[6
]}

Hesketh, John E. ^{[4
]}

Hughes, David J. ^{[47
]}

机构：

[1] Emory Univ, Dept Epidemiol, Rollins Sch Publ Hlth, Atlanta, GA 30322 USA

[2] Emory Univ, Winship Canc Inst, Atlanta, GA 30322 USA

[3] Int Agcy Res Canc, Sect Nutr & Metab, F-69372 Lyon, France

[4] Newcastle Univ, Sch Biomed Sci, Newcastle Upon Tyne NE1 7RU, Tyne & Wear, England

[5] Univ Med Sch, Inst Expt Endocrinol, D-13353 Berlin, Germany

[6] Imperial Coll London, Sch Publ Hlth, Dept Epidemiol & Biostat, London W2 1PG, England

[7] Aarhus Univ, Dept Publ Hlth, Sect Epidemiol, DK-8000 Aarhus, Denmark

[8] Danish Canc Soc, Res Ctr, Diet Genes & Environm Unit, DK-2100 Copenhagen, Denmark

[9] Univ Paris Saclay, Univ Paris Sud, Fac Med UVSQ, INSERM,Fac Med,CESP, F-94805 Villejuif, France

[10] Ctr Res Epidemiol & Populat Hlth CESP, F-94805 Villejuif, France

[11] Univ Paris 05, Lab Appl Math, MAP5 UMR CNRS 8145, F-75270 Paris, France

[12] German Canc Res Ctr, Div Canc Epidemiol, D-69120 Heidelberg, Germany

[13] German Inst Human Nutr Potsdam Rehbrucke, Dept Epidemiol, D-14558 Nuthetal, Germany

[14] Hellen Hlth Fdn, Athens 11527, Greece

[15] Univ Athens, ATTIKON Univ Hosp, Pulm Med Dept 2, Sch Med, Haidari 10679, Greece

[16] Univ Athens, Sch Med, Dept Crit Care Med & Pulm Serv 1, Athens 10676, Greece

[17] Civ MP Arezzo Hosp, Canc Registry, I-97100 Ragusa, Italy

[18] Civ MP Arezzo Hosp, Dept Histopathol, I-97100 Ragusa, Italy

[19] Univ Naples Federico II, Dept Clin Med & Surg, I-80138 Naples, Italy

[20] Canc Res & Prevent Inst ISPO, Canc Risk Factors & Life Style Epidemiol Unit, I-50141 Florence, Italy

[21] Natl Canc Inst, IRCCS Fdn, Epidemiol & Prevent Unit, I-20133 Milan, Italy

[22] IIGM, Mol & Genet Epidemiol Unit, I-10126 Turin, Italy

[23] Natl Inst Publ Hlth & Environm RIVM, Dept Determinants Chron Dis DCD, NL-3720 Bilthoven, Netherlands

[24] Univ Med Ctr, Dept Gastroenterol & Hepatol, NL-3584 CX Utrecht, Netherlands

[25] Univ Malaya, Fac Med, Dept Social & Prevent Med, Kuala Lumpur 50603, Malaysia

[26] Univ Utrecht, Inst Risk Assessment Sci, NL-3512 JE Utrecht, Netherlands

[27] Inst Population Based Canc Res, Canc Registry Norway, Dept Res, N-0304 Oslo, Norway

[28] Karolinska Inst, Dept Med Epidemiol & Biostat, SE-17177 Stockholm, Sweden

[29] Univ Helsinki, Folkhalsan Res Ctr, Genet Epidemiol Grp, Helsinki 00014, Finland

[30] Univ Helsinki, Fac Med, Helsinki 00014, Finland

[31] Univ Tromso, Arctic Univ Norway, Dept Community Med, N-9019 Tromso, Norway

[32] Catalan Inst Oncol ICO IDIBELL, Unit Nutr & Canc, Barcelona 08908, Spain

[33] Publ Hlth Directorate, EPIC Asturias, Oviedo 33006, Asturias, Spain

[34] IMIB Arrixaca, Murcia Reg Hlth Council, Dept Epidemiol, Murcia 30008, Spain

[35] CIBER Epidemiol & Publ Hlth CIBERESP, Madrid 28029, Spain

[36] Univ Granada, Univ Hosp Granada, Inst Biosanit Res, Andalucia Sch Publ Hlth, Granada 18011, Spain

[37] Navarra Publ Hlth Inst, Epidemiol Prevent & Promot Hlth Serv, Pamplona 31003, Spain

[38] Navarra Inst Hlth Res IdiSNA, Pamplona 31008, Spain

[39] Umea Univ, Dept Med Biosci, Pathol, S-90187 Umea, Sweden

[40] Umea Univ, Dept Radiat Sci, Oncol, S-90187 Umea, Sweden

[41] Univ Oxford, Nuffield Dept Populat Hlth, Canc Epidemiol Unit, Oxford OX3 7LF, England

[42] Univ Cambridge, MRC Epidemiol Unit, Cambridge CB2 0QQ, England

[43] Univ Cambridge, Addenbrookes Hosp, Sch Clin Med, Clin Gerontol Unit, Cambridge CB2 0QQ, England

[44] Univ Ioannina, Sch Med, Dept Hyg & Epidemiol, GR-45110 Ioannina, Greece

[45] Bjorknes Univ Coll, Dept Nutr, N-0456 Oslo, Norway

[46] Oslo Univ Hosp, Dept Endocrinol Morbid Obes & Prevent Med, N-0372 Oslo, Norway

[47] Univ Coll Dublin, UCD Conway Inst, Canc Biol & Therapeut Grp, Sch Biomol & Biomed Sci, Dublin D04 V1W8, Ireland

来源：

NUTRIENTS | 2019年 / 11卷 / 04期

基金：

英国医学研究理事会;

关键词：

selenium; selenium status; selenoprotein gene variation; selenium pathway; colorectal neoplasms; selenoprotein P; prospective cohort; colorectal cancer risk; genetic epidemiology; biomarkers; FRIZZLED-RELATED PROTEIN; GENETIC-VARIANTS; CROHNS-DISEASE; SUSCEPTIBILITY; POLYMORPHISM; METAANALYSIS; MEGALIN; HEALTH; ARCHITECTURE; BIOMARKERS;

D O I：

10.3390/nu11040935

中图分类号：

R15 [营养卫生、食品卫生]; TS201 [基础科学];

学科分类号：

100403 ;

摘要：

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.

引用

页数：19

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