title: Common genetic variants related to genomic integrity and risk of papillary thyroid cancer.
abstract: DNA damage is an important mechanism in carcinogenesis, so genes related to maintaining genomic integrity may influence papillary thyroid cancer (PTC) risk. Candidate gene studies targeting some of these genes have identified only a few polymorphisms associated with risk of PTC. Here, we expanded the scope of previous candidate studies by increasing the number and coverage of genes related to maintenance of genomic integrity. We evaluated 5077 tag single-nucleotide polymorphisms (SNPs) from 340 candidate gene regions hypothesized to be involved in DNA repair, epigenetics, tumor suppression, apoptosis, telomere function and cell cycle control and signaling pathways in a case-control study of 344 PTC cases and 452 matched controls. We estimated odds ratios for associations of single SNPs with PTC risk and combined P values for SNPs in the same gene region or pathway to obtain gene region-specific or pathway-specific P values using adaptive rank-truncated product methods. Nine SNPs had P values <0.0005, three of which were in HDAC4 and were inversely related to PTC risk. After multiple comparisons adjustment, no SNPs remained associated with PTC risk. Seven gene regions were associated with PTC risk at P < 0.01, including HUS1, ALKBH3, HDAC4, BAK1, FAF1_CDKN2C, DACT3 and FZD6. Our results suggest a possible role of genes involved in maintenance of genomic integrity in relation to risk of PTC.
authors.affiliation: Radiation Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health/DHHS, 6120 Executive Boulevard, Rockville, MD 20852-7244, USA. netagil@mail.nih.gov
authors.forename: Gila
authors.initials: G
authors.lastname: Neta
authors.forename: Alina V
authors.initials: AV
authors.lastname: Brenner
authors.forename: Erich M
authors.initials: EM
authors.lastname: Sturgis
authors.forename: Ruth M
authors.initials: RM
authors.lastname: Pfeiffer
authors.forename: Amy A
authors.initials: AA
authors.lastname: Hutchinson
authors.forename: Briseis
authors.initials: B
authors.lastname: Aschebrook-Kilfoy
authors.forename: Meredith
authors.initials: M
authors.lastname: Yeager
authors.forename: Li
authors.initials: L
authors.lastname: Xu
authors.forename: William
authors.initials: W
authors.lastname: Wheeler
authors.forename: Michael
authors.initials: M
authors.lastname: Abend
authors.forename: Elaine
authors.initials: E
authors.lastname: Ron
authors.forename: Margaret A
authors.initials: MA
authors.lastname: Tucker
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Chanock
authors.forename: Alice J
authors.initials: AJ
authors.lastname: Sigurdson
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000235:genetics*; D002277:Carcinoma; D002291:Carcinoma, Papillary; D016022:Case-Control Studies; D005260:Female; D020869:Gene Expression Profiling; D020022:Genetic Predisposition to Disease; D042822:Genomic Instability; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D020411:Oligonucleotide Array Sequence Analysis; D016133:Polymerase Chain Reaction; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D011379:Prognosis; D012307:Risk Factors; D000077273:Thyroid Cancer, Papillary; D013964:Thyroid Neoplasms / Q000235:genetics*; D055815:Young Adult
chemical_list: D014408:Biomarkers, Tumor