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Age at diagnosis and gender modify the risk of 9q22 and 14q13 polymorphisms for papillary thyroid carcinoma
Affiliations- Department of Nuclear Medicine and Endocrine Oncology, Maria Sklodowska-Curie Memorial Cancer Centre and Institute of Oncology, Gliwice Branch, Poland, Poland
- Institute of Automatic Control, Silesian University of Technology, Gliwice, Poland, Poland
- Department of Genomic Medicine, Medical University of Warsaw, Poland
- Centre of New Technologies, CENT, University of Warsaw, Poland
- Clinic of Oncology and Reconstructive Surgery, Maria Sklodowska-Curie Memorial Cancer Centre and Institute of Oncology, Gliwice Branch, Poland, Poland
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Abstract
Introduction: Papillary thyroid cancer (PTC) shows familial occurrence, and some susceptibility single nucleotide polymorphisms (SNPs) have been identified in FOXE1 and near the NKX2-1 locus. The aim of our study was to analyse the association of PTC risk with SNPs in FOXE1 (rs965513, rs1867277, rs1443434) and near the NKX2-1 locus (rs944289) in a Polish population, and, in the second step, the interaction between SNPs and patient-related factors (age at diagnosis and gender).
Material and methods: A total of 2243 DNA samples from PTC patients and 1160 controls were included in the study. The SNP analysis was performed with the allelic discrimination technique.
Results: There were significant associations of all SNPs with PTC (rs965513 odds ratio [OR] = 1.72, p = 8 × 10-7; rs1867277 OR = 1.59, p = 1 × 10-6; rs1443434 OR = 1.53, p = 1 × 10-5; rs944289 OR = 1.52, p = 4 × 10-5). Logistic regression analysis revealed an increased PTC risk in the interaction of rs944289 with age at diagnosis (OR = 1.01 per year, p = 6 × 10-4) and a decreased PTC risk in the interaction of male gender with the GGT FOXE1 protective haplotype (OR = 0.69, p = 0.01).
Conclusions: the association between PTC and all analysed SNPs was confirmed. It was also shown that patient-related factors modify the predisposition to PTC by increasing the risk for rs944289 per year of age, and by enhancing the protective effect of the FOXE1 GGT haplotype in men.
Abstract
Introduction: Papillary thyroid cancer (PTC) shows familial occurrence, and some susceptibility single nucleotide polymorphisms (SNPs) have been identified in FOXE1 and near the NKX2-1 locus. The aim of our study was to analyse the association of PTC risk with SNPs in FOXE1 (rs965513, rs1867277, rs1443434) and near the NKX2-1 locus (rs944289) in a Polish population, and, in the second step, the interaction between SNPs and patient-related factors (age at diagnosis and gender).
Material and methods: A total of 2243 DNA samples from PTC patients and 1160 controls were included in the study. The SNP analysis was performed with the allelic discrimination technique.
Results: There were significant associations of all SNPs with PTC (rs965513 odds ratio [OR] = 1.72, p = 8 × 10-7; rs1867277 OR = 1.59, p = 1 × 10-6; rs1443434 OR = 1.53, p = 1 × 10-5; rs944289 OR = 1.52, p = 4 × 10-5). Logistic regression analysis revealed an increased PTC risk in the interaction of rs944289 with age at diagnosis (OR = 1.01 per year, p = 6 × 10-4) and a decreased PTC risk in the interaction of male gender with the GGT FOXE1 protective haplotype (OR = 0.69, p = 0.01).
Conclusions: the association between PTC and all analysed SNPs was confirmed. It was also shown that patient-related factors modify the predisposition to PTC by increasing the risk for rs944289 per year of age, and by enhancing the protective effect of the FOXE1 GGT haplotype in men.
Keywords
SNP; carcinoma papillare; age at diagnosis; gender
About this articleTitle
Age at diagnosis and gender modify the risk of 9q22 and 14q13 polymorphisms for papillary thyroid carcinoma
Journal
Issue
Article type
Original paper
Pages
283-289
Published online
2017-06-21
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1890
Article views/downloads
1874
DOI
Pubmed
Bibliographic record
Endokrynol Pol 2017;68(3):283-289.
Keywords
SNP
carcinoma papillare
age at diagnosis
gender
Authors
Dorota Kula
Michał Kalemba
Zbigniew Puch
Joanna Polańska
Michał Świerniak
Dagmara Rusinek
Jadwiga Żebracka-Gala
Małgorzata Kowalska
Daria Handkiewicz-Junak
Monika Kowal
Tomasz Tyszkiewicz
Ewelina Piasna
Agnieszka Czarniecka
Agnieszka Pawlaczek
Jolanta Krajewska
Sylwia Szpak-Ulczok
Barbara Jarząb
References (25)- Landa I, Robledo M, Landa I, et al. Association studies in thyroid cancer susceptibility: are we on the right track? J Mol Endocrinol. 2011; 47(1): R43–R58.
- Liyanarachchi S, Wojcicka A, Li W, et al. Cumulative risk impact of five genetic variants associated with papillary thyroid carcinoma. Thyroid. 2013; 23(12): 1532–1540.
- He H, Nagy R, Liyanarachchi S, et al. A susceptibility locus for papillary thyroid carcinoma on chromosome 8q24. Cancer Res. 2009; 69(2): 625–631.
- Landa I, Ruiz-Llorente S, Montero-Conde C, et al. The variant rs1867277 in FOXE1 gene confers thyroid cancer susceptibility through the recruitment of USF1/USF2 transcription factors. PLoS Genet. 2009; 5(9): e1000637.
- Gudmundsson J, Sulem P, Gudbjartsson DF, et al. Common variants on 9q22.33 and 14q13.3 predispose to thyroid cancer in European populations. Nat Genet. 2009; 41(4): 460–464.
- Kula D, Kalemba M, Jurecka-Lubieniecka B, et al. Genetic predisposition to papillary thyroid cancer. Endokrynol Pol. 2010; 61(5): 486–489.
- Adjadj E, Schlumberger M, de Vathaire F. Germ-line DNA polymorphisms and susceptibility to differentiated thyroid cancer. Lancet Oncol. 2009; 10(2): 181–190.
- Penna-Martinez M, Epp F, Kahles H, et al. FOXE1 association with differentiated thyroid cancer and its progression. Thyroid. 2014; 24(5): 845–851.
- Matsuse M, Takahashi M, Mitsutake N, et al. The FOXE1 and NKX2-1 loci are associated with susceptibility to papillary thyroid carcinoma in the Japanese population. J Med Genet. 2011; 48(9): 645–648.
- Takahashi M, Saenko VA, Rogounovitch TI, et al. The FOXE1 locus is a major genetic determinant for radiation-related thyroid carcinoma in Chernobyl. Hum Mol Genet. 2010; 19(12): 2516–2523.
- Bullock M, Duncan EL, O'Neill C, et al. Association of FOXE1 polyalanine repeat region with papillary thyroid cancer. J Clin Endocrinol Metab. 2012; 97(9): E1814–E1819.
- Tomaz RA, Sousa I, Silva JG, et al. FOXE1 polymorphisms are associated with familial and sporadic nonmedullary thyroid cancer susceptibility. Clin Endocrinol (Oxf). 2012; 77(6): 926–933.
- Jones AM, Howarth KM, Martin L, et al. TCUKIN Consortium. Thyroid cancer susceptibility polymorphisms: confirmation of loci on chromosomes 9q22 and 14q13, validation of a recessive 8q24 locus and failure to replicate a locus on 5q24. J Med Genet. 2012; 49(3): 158–163.
- Bonora E, Rizzato C, Diquigiovanni C, et al. NMTC Consortium. The FOXE1 locus is a major genetic determinant for familial nonmedullary thyroid carcinoma. Int J Cancer. 2014; 134(9): 2098–2107.
- Köhler A, Chen B, Gemignani F, et al. Genome-wide association study on differentiated thyroid cancer. J Clin Endocrinol Metab. 2013; 98(10): E1674–E1681.
- Ai L, Yu Y, Liu X, et al. Are the SNPs of NKX2-1 associated with papillary thyroid carcinoma in the Han population of Northern China? Front Med. 2014; 8(1): 113–117.
- Damiola F, Byrnes G, Moissonnier M, et al. Contribution of ATM and FOXE1 (TTF2) to risk of papillary thyroid carcinoma in Belarusian children exposed to radiation. Int J Cancer. 2014; 134(7): 1659–1668.
- Kang J, Deng XZ, Fan YB, et al. Relationships of FOXE1 and ATM genetic polymorphisms with papillary thyroid carcinoma risk: a meta-analysis. Tumour Biol. 2014; 35(7): 7085–7096.
- Zhu H, Xi Q, Liu L, et al. Quantitative assessment of common genetic variants on FOXE1 and differentiated thyroid cancer risk. PLoS One. 2014; 9(1): e87332.
- Zhuang Y, Wu W, Liu H, et al. Common genetic variants on FOXE1 contributes to thyroid cancer susceptibility: evidence based on 16 studies. Tumour Biol. 2014; 35(6): 6159–6166.
- Ai L, Liu X, Yao Y, et al. Associations between rs965513/rs944289 and papillary thyroid carcinoma risk: a meta-analysis. Endocrine. 2014; 47(2): 428–434.
- Bychkov A, Saenko V, Nakashima M, et al. Patterns of FOXE1 expression in papillary thyroid carcinoma by immunohistochemistry. Thyroid. 2013; 23(7): 817–828.
- Machens A, Hauptmann S, Dralle H. Disparities between male and female patients with thyroid cancers: sex difference or gender divide? Clin Endocrinol (Oxf). 2006; 65(4): 500–505.
- Choi H, Lim JAh, Ahn HY, et al. Secular trends in the prognostic factors for papillary thyroid cancer. Eur J Endocrinol. 2014; 171(5): 667–675.
- Fortunato RS, Ferreira ACF, Hecht F, et al. Sexual dimorphism and thyroid dysfunction: a matter of oxidative stress? J Endocrinol. 2014; 221(2): R31–R40.
