title: Selected single-nucleotide polymorphisms in FOXE1, SERPINA5, FTO, EVPL, TICAM1 and SCARB1 are associated with papillary and follicular thyroid cancer risk: replication study in a German population.
abstract: Several single-nucleotide polymorphisms (SNPs) have been associated with papillary and follicular thyroid cancer (PTC and FTC, respectively) risk, but few have replicated. After analyzing 17525 tag SNPs in 1129 candidate genes, we found associations with PTC risk in SERPINA5, FTO, HEMGN (near FOXE1) and other genes. Here, we report results from a replication effort in a large independent PTC/FTC case-control study conducted in Germany. We evaluated the best tagging SNPs from our previous PTC study and additionally included SNPs in or near FOXE1 and NKX2-1 genes, known susceptibility loci for thyroid cancer. We genotyped 422 PTC and 130 FTC cases and 752 controls recruited from three German clinical centers. We used polytomous logistic regression to simultaneously estimate PTC and FTC associations for 79 SNPs based on log-additive models. We assessed effect modification by body mass index (BMI), gender and age for all SNPs, and selected SNP by SNP interactions. We confirmed associations with PTC and SNPs in FOXE1/HEMGN, SERPINA5 (rs2069974), FTO (rs8047395), EVPL (rs2071194), TICAM1 (rs8120) and SCARB1 (rs11057820) genes. We found associations with SNPs in FOXE1, SERPINA5, FTO, TICAM1 and HSPA6 and FTC. We found two significant interactions between FTO (rs8047395) and BMI (P = 0.0321) and between TICAM1 (rs8120) and FOXE1 (rs10984377) (P = 0.0006). Besides the known associations with FOXE1 SNPs, we confirmed additional PTC SNP associations reported previously. We also found several new associations with FTC risk and noteworthy interactions. We conclude that multiple variants and host factors might interact in complex ways to increase risk of PTC and FTC.
authors.forename: Alice J
authors.initials: AJ
authors.lastname: Sigurdson
authors.forename: Alina V
authors.initials: AV
authors.lastname: Brenner
authors.forename: James A
authors.initials: JA
authors.lastname: Roach
authors.affiliation: Department of Transfusion Medicine and.
authors.forename: Lilia
authors.initials: L
authors.lastname: Goudeva
authors.affiliation: Department of Nuclear Medicine, Hannover Medical School, Hannover, Germany.
authors.forename: Jörg A
authors.initials: JA
authors.lastname: Müller
authors.affiliation: Department of Nuclear Medicine, University Hospital Würzburg, Würzburg, Germany.
authors.forename: Kai
authors.initials: K
authors.lastname: Nerlich
authors.affiliation: Department of Nuclear Medicine, University Hospital Würzburg, Würzburg, Germany.
authors.forename: Christoph
authors.initials: C
authors.lastname: Reiners
authors.affiliation: Department of Surgery, Federal Armed Forces Hospital, Koblenz, Germany.
authors.forename: Robert
authors.initials: R
authors.lastname: Schwab
authors.affiliation: Research Unit of Molecular Epidemiology and.|Institute of Epidemiology II, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Germany.
authors.forename: Liliane
authors.initials: L
authors.lastname: Pfeiffer
authors.affiliation: Research Unit of Molecular Epidemiology and.|Institute of Epidemiology II, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Germany.
authors.forename: Melanie
authors.initials: M
authors.lastname: Waldenberger
authors.forename: Melissa
authors.initials: M
authors.lastname: Braganza
authors.affiliation: Department of Head and Neck Surgery, The University of Texas M.D. Anderson Cancer Center, Houston, TX 77030, USA.
authors.forename: Li
authors.initials: L
authors.lastname: Xu
authors.affiliation: Department of Head and Neck Surgery, The University of Texas M.D. Anderson Cancer Center, Houston, TX 77030, USA.
authors.forename: Erich M
authors.initials: EM
authors.lastname: Sturgis
authors.affiliation: Laboratory of Translational Genetics and.
authors.forename: Meredith
authors.initials: M
authors.lastname: Yeager
authors.affiliation: Laboratory of Translational Genetics and.
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Chanock
authors.affiliation: Biostatistics Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD 20892, USA.
authors.forename: Ruth M
authors.initials: RM
authors.lastname: Pfeiffer
authors.affiliation: Bundeswehr Institute of Radiobiology, University of Ulm, Neuherbergstr. 11, Munich 80937, Germany and.
authors.forename: Michael
authors.initials: M
authors.lastname: Abend
authors.affiliation: Department of Hematology, Hemostasis, Oncology and Stem Cell Transplantation, Hannover Medical School, Hannover, Germany.
authors.forename: Matthias
authors.initials: M
authors.lastname: Port
mesh_terms: D033942:Adaptor Proteins, Vesicular Transport / Q000235:genetics*; D018263:Adenocarcinoma, Follicular / Q000235:genetics* / Q000473:pathology; D000328:Adult; D000368:Aged; D000071516:Alpha-Ketoglutarate-Dependent Dioxygenase FTO / Q000235:genetics*; D002277:Carcinoma / Q000235:genetics* / Q000473:pathology; D002291:Carcinoma, Papillary; D005260:Female; D051858:Forkhead Transcription Factors / Q000235:genetics*; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D005838:Genotype; D005858:Germany; D006801:Humans; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D018046:Protein C Inhibitor / Q000235:genetics*; D012307:Risk Factors; D051122:Scavenger Receptors, Class B / Q000235:genetics*; D000077273:Thyroid Cancer, Papillary; D013964:Thyroid Neoplasms / Q000235:genetics* / Q000473:pathology
chemical_list: D033942:Adaptor Proteins, Vesicular Transport; C106894:FOXE1 protein, human; D051858:Forkhead Transcription Factors; D018046:Protein C Inhibitor; C495124:SCARB1 protein, human; C534934:SERPINA5 protein, human; D051122:Scavenger Receptors, Class B; C470409:TICAM1 protein, human; D000071516:Alpha-Ketoglutarate-Dependent Dioxygenase FTO; C526492:FTO protein, human