nach oben

Endocrine

Erschienen in:

01.04.2014 | Original Article

Association of the ATM gene polymorphisms with papillary thyroid cancer

verfasst von: Yulu Gu, Yaqin Yu, Lizhe Ai, Jieping Shi, Xiaoli Liu, Hui Sun, Yawen Liu

Erschienen in: Endocrine | Ausgabe 3/2014

Einloggen, um Zugang zu erhalten

Abstract

Papillary thyroid cancer (PTC) is the most common type of thyroid cancer, yet few genetic markers of PTC risk useful for screening exist. Our study aimed to evaluate the association between single nucleotide polymorphisms (SNPs) of the ataxia telangiectasia mutated (ATM) gene and PTC risk. 358 patients with PTC and 360 healthy controls were included in the case–control study. Four ATM SNPs (rs664677, rs373759, rs4988099, and rs189037) were genotyped by matrix-assisted laser desorption/ionization time of flight mass spectrometry (MALDI-TOF-MS). The analysis of genetic data was performed using the SNPStats program. The allele frequencies and genotype distributions of the four ATM SNPs were not different between PTC patients and controls. We did not observe any tendency of increasing the frequency of the risk allele from controls, patients without metastasis to patients with metastasis (P _trend > 0.05). Interestingly, the AG genotype of rs373759 was associated with PTC risk under an overdominant model of inheritance (adjusted OR = 1.38; 95 % CI, 1.03–1.87; P = 0.03). No haplotype was observed to be significantly associated with PTC risk. Our results suggest that heterozygosity for the ATM rs373759 polymorphism may be a potential risk factor for PTC.

K. Jazdzewski, E.L. Murray, K. Franssila, B. Jarzab, D.R. Schoenberg, A. de la Chapelle, Common SNP in pre-miR-146a decreases mature miR expression and predisposes to papillary thyroid carcinoma. Proc. Natl. Acad. Sci. USA. 105(20), 7269–7274 (2008). doi:10.1073/pnas.0802682105 PubMedCentralPubMedCrossRef

J.C. Xing, R.P. Tufano, A.K. Murugan, D.X. Liu, G. Wand, P.W. Ladenson, M.Z. Xing, B. Trink, Single nucleotide polymorphism rs17849071 G/T in the PIK3CA gene is inversely associated with follicular thyroid cancer and PIK3CA amplification. PLoS. One. (2012). doi:10.1371/journal.pone.0049192

I.K. Hong, Y.G. Eun, D.H. Chung, K.H. Kwon, D.Y. Kim, Association of the oncostatin M receptor gene polymorphisms with papillary thyroid cancer in the korean population. Clin. Exp. Otorhinolar. 4(4), 193–198 (2011). doi:10.3342/ceo.2011.4.4.193 CrossRef

I. Landa, M. Robledo, Association studies in thyroid cancer susceptibility: are we on the right track? J. Mol. Endocrinol. 47(1), R43–R58 (2011). doi:10.1530/Jme-11-0005 CrossRef

P.J. Hsiao, M.Y. Lu, F.Y. Chiang, S.J. Shin, Y.D. Tai, S.H.H. Juo, Vascular endothelial growth factor gene polymorphisms in thyroid cancer. J. Endocrinol. 195(2), 265–270 (2007). doi:10.1677/Joe-07-0395 PubMedCrossRef

L. Xu, E.C. Morari, Q.Y. Wei, E.M. Sturgis, L.S. Ward, Functional variations in the ATM gene and susceptibility to differentiated thyroid carcinoma. J. Clin. Endocr. Metab. 97(6), 1913–1921 (2012). doi:10.1210/Jc.2011-3299 PubMedCentralPubMedCrossRef

D. Chakravarty, E. Santos, M. Ryder, J.A. Knauf, X.H. Liao, B.L. West, G. Bollag, R. Kolesnick, T.H. Thin, N. Rosen, P. Zanzonico, S.M. Larson, S. Refetoff, R. Ghossein, J.A. Fagin, Small-molecule MAPK inhibitors restore radioiodine incorporation in mouse thyroid cancers with conditional BRAF activation. J. Clin. Invest. 121(12), 4700–4711 (2011). doi:10.1172/JCI46382 PubMedCentralPubMedCrossRef

M.A.A. Xing, K.A. Carson, D. Viola, R. Elisei, B. Bendlova, L. Yip, C. Mian, F. Vianello, R.M. Tuttle, E. Robenshtok, J.A. Fagin, E. Puxeddu, L. Fugazzola, A. Czarniecka, B. Jarzab, C.J. O’Neill, Sywak, A.K. Lam, G. Riesco-Eizaguirre, P. Santisteban, H. Nakayama, R.P. Tufano, S.I. Pai, M.A. Zeiger, W.H. Westra, D.P. Clark, R. Clifton-Bligh, D. Sidransky, P.W. Ladenson, V. Sykorova, Association between BRAF V600E mutation and mortality in patients with papillary thyroid cancer. JAMA. 309(14), 1493–1501 (2013)PubMedCentralPubMedCrossRef

C. Nucera, M.A. Nehs, S.S. Nagarkatti, P.M. Sadow, M. Mekel, A.H. Fischer, P.S. Lin, G.E. Bollag, J. Lawler, R.A. Hodin, S. Parangi, Targeting BRAFV600E with PLX4720 displays potent antimigratory and anti-invasive activity in preclinical models of human thyroid cancer. Oncol 16(3), 296–309 (2011). doi:10.1634/theoncologist.2010-0317 CrossRef

10.

C. Nucera, A. Porrello, Z.A. Antonello, M. Mekel, M.A. Nehs, T.J. Giordano, D. Gerald, L.E. Benjamin, C. Priolo, E. Puxeddu, B-RafV600E and thrombospondin-1 promote thyroid cancer progression. Proc. Natl. Acad. Sci. 107(23), 10649–10654 (2010)PubMedCentralPubMedCrossRef

11.

M. Takahashi, V.A. Saenko, T.I. Rogounovitch, T. Kawaguchi, V.M. Drozd, H. Takigawa-Imamura, N.M. Akulevich, C. Ratanajaraya, N. Mitsutake, N. Takamura, L.I. Danilova, M.L. Lushchik, Y.E. Demidchik, S. Heath, R. Yamada, M. Lathrop, F. Matsuda, S. Yamashita, The FOXE1 locus is a major genetic determinant for radiation-related thyroid carcinoma in chernobyl. Hum. Mol. Genet. 19(12), 2516–2523 (2010). doi:10.1093/Hmg/Ddq123 PubMedCrossRef

12.

F. Basolo, R. Giannini, P. Faviana, G. Fontanini, A.P. Malizia, C. Ugolini, R. Elisei, P. Miccoli, A. Toniolo, Thyroid papillary carcinoma: preliminary evidence for a germ-line single nucleotide polymorphism in the Fas gene. J. Endocrinol. 182(3), 479–484 (2004). doi:10.1677/joe.0.1820479 PubMedCrossRef

13.

M.F. Lavin, S. Scott, N. Gueven, S. Kozlov, P.A. Cheng, P. Chen, Functional consequences of sequence alterations in the ATM gene. DNA. Repair 3(8–9), 1197–1205 (2004). doi:10.1016/j.dnarep.2004.03.011 PubMedCrossRef

14.

K.K. Khanna, S.P. Jackson, DNA double-strand breaks: signaling, repair and the cancer connection. Nat. Genet. 27(3), 247–254 (2001). doi:10.1038/85798 PubMedCrossRef

15.

G. Rotman, Y. Shiloh, ATM: a mediator of multiple responses to genotoxic stress. Oncogene. 18(45), 6135–6144 (1999). doi:10.1038/sj.onc.1203124 PubMedCrossRef

16.

Y. Shiloh, ATM and related protein kinases: safeguarding genome integrity. Nat. Rev. Cancer 3(3), 155–168 (2003). doi:10.1038/Nrc1011 PubMedCrossRef

17.

L. Ricaud, C. Proux, J.P. Renou, O. Pichon, S. Fochesato, P. Ortet, M.H. Montane, ATM-Mediated transcriptional and developmental responses to gamma-rays in arabidopsis. PLoS. One (2007). doi:10.1371/journal.pone.0000430 PubMedCentralPubMed

18.

N.M. Akulevich, V.A. Saenko, T.I. Rogounovitch, V.M. Drozd, E.F. Lushnikov, V.K. Ivanov, N. Mitsutake, R. Kominami, S. Yamashita, Polymorphisms of DNA damage response genes in radiation-related and sporadic papillary thyroid carcinoma. Endocr-Relat. Cancer 16(2), 491–503 (2009). doi:10.1677/Erc-08-0336 PubMedCrossRef

19.

L. Zhao, A.H. Gu, G.X. Ji, P. Zou, P. Zhao, A.L. Lu, The association between ATM IVS 22-77 T > C and cancer risk: a meta-analysis. PLoS. One (2012). doi:10.1371/journal.pone.0029479

20.

K. Savitsky, A. Bar-Shira, S. Gilad, G. Rotman, Y. Ziv, L. Vanagaite, D.A. Tagle, S. Smith, T. Uziel, S. Sfez, A single ataxia telangiectasia gene with a product similar to PI-3 kinase. Science. 268(5218), 1749–1753 (1995). doi:10.1126/science.7792600 PubMedCrossRef

21.

T.A. Buchholz, M.M. Weil, C.L. Ashorn, E.A. Strom, A. Sigurdson, M. Bondy, R. Chakraborty, J.D. Cox, M.D. McNeese, M.D. Story, A Ser49Cys variant in the ataxia telangiectasia, mutated, gene that is more common in patients with breast carcinoma compared with population controls. Cancer. 100(7), 1345–1351 (2004). doi:10.1002/Cncr.20133 PubMedCrossRef

22.

A. Meyer, B. Wilhelm, T. Dork, M. Bremer, R. Baumann, J.H. Karstens, S. Machtens, ATM missense variant P1054R predisposes to prostate cancer. Radiother. Oncol. 83(3), 283–288 (2007). doi:10.1002/j.radonc.2007.04.029 PubMedCrossRef

23.

S. Angele, A. Falconer, S.M. Edwards, T. Dork, M. Bremer, N. Moullan, B. Chapot, K. Muir, R. Houlston, A.R. Norman, S. Bullock, Q. Hope, J. Meitz, D. Dearnaley, A. Dowe, C. Southgate, A. Ardern-Jones, D.F. Easton, R.A. Eeles, J. Hall, The Cancer Research UK/British Prostate Group/Association of Urological Surgeons, Section of Oncology Collaborators, ATM polymorphisms as risk factors for prostate cancer development. Brit. J. Cancer. 91(4), 783–787 (2004). doi:10.1038/sj.bjc.6602007 PubMedCentralPubMed

24.

Y.L. Zheng, O. Kosti, C.A. Loffredo, E. Bowman, L. Mechanic, D. Perlmutter, R. Jones, P.G. Shields, C.C. Harris, Elevated lung cancer risk is associated with deficiencies in cell cycle checkpoints: genotype and phenotype analyses from a case-control study. Int. J. Cancer 126(9), 2199–2210 (2010). doi:10.1002/Ijc.24771 PubMedCentralPubMed

25.

A. Cox, A.M. Dunning, M. Garcia-Closas, S. Balasubramanian, M.W.R. Reed, K.A. Pooley, S. Scollen, C. Baynes, B.A.J. Ponder, S. Chanock, J. Lissowska, L. Brinton, B. Peplonska, M.C. Southey, J.L. Hopper, M.R.E. McCredie, G.G. Giles, O. Fletcher, N. Johnson, I.D. Silva, L. Gibson, S.E. Bojesen, B.G. Nordestgaard, C.K. Axelsson, D. Torres, U. Hamann, C. Justenhoven, H. Brauch, J. Chang-Claude, S. Kropp, A. Risch, S. Wang-Gohrke, P. Schurmann, N. Bogdanova, T. Dork, R. Fagerholm, K. Aaltonen, C. Blomqvist, H. Nevanlinna, S. Seal, A. Renwick, M.R. Stratton, N. Rahman, S. Sangrajrang, D. Hughes, F. Odefrey, P. Brennan, A.B. Spurdle, G. Chenevix-Trench, J. Beesley, A. Mannermaa, J. Hartikainen, V. Kataja, V.M. Kosma, F.J. Couch, J.E. Olson, E.L. Goode, A. Broeks, M.K. Schmidt, F.B.L. Hogervorst, L.J. Van’t Veer, D. Kang, K.Y. Yoo, D.Y. Noh, S.H. Ahn, S. Wedren, P. Hall, Y.L. Low, J.J. Liu, R.L. Milne, G. Ribas, A. Gonzalez-Neira, J. Benitez, A.J. Sigurdson, D.L. Stredrick, B.H. Alexander, J.P. Struewing, P.D.P. Pharoah, D.F. Easton, K.C.F. Consortium, B.C.A. Consortium, A common coding variant in CASP8 is associated with breast cancer risk. Nat. Genet. 39(3), 352–358 (2007). doi:10.1038/Ng1981 PubMedCrossRef

26.

D.L. Stredrick, M. Garcia-Closas, M.A. Pineda, P. Bhatti, B.H. Alexander, M.M. Doody, J. Lissowska, B. Peplonska, L.A. Brinton, S.J. Chanock, J.P. Struewing, A.J. Sigurdson, The ATM missense mutation p.Ser49Cys (c.146C > G) and the risk of breast cancer. Hum. Mutat. 27(6), 538–544 (2006). doi:10.1002/humu.20323 PubMedCentralPubMedCrossRef

27.

S.L. Dombernowsky, M. Weischer, K.H. Allin, S.E. Bojesen, A. Tybjaerg-Hansen, B.G. Nordestgaard, Risk of cancer by ATM missense mutations in the general population. J. Clin. Oncol. 26(18), 3057–3062 (2008). doi:10.1200/JCO.2007.14.6613 PubMedCrossRef

28.

M. Ahmed, N. Rahman, ATM and breast cancer susceptibility. Oncogene. 25(43), 5906–5911 (2006). doi:10.1038/sj.onc.1209873 PubMedCrossRef

29.

A. Renwick, D. Thompson, S. Seal, P. Kelly, T. Chagtai, M. Ahmed, B. North, H. Jayatilake, R. Barfoot, K. Spanova, L. McGuffog, D.G. Evans, D. Eccles, D.F. Easton, M.R. Stratton, N. Rahman, ATM mutations that cause ataxia-telangiectasia are breast cancer susceptibility alleles. Nat. Genet. 38(8), 873–875 (2006). doi:10.1038/ng1837 PubMedCrossRef

30.

T. Chen, B.R. Dong, Z.C. Lu, B.C. Tian, J.A. Zhang, J.L. Zhou, H.M. Wu, Y.L. Zhang, J.H. Wu, P. Lin, J. Zhang, H. Xu, X.M. Mo, A functional single nucleotide polymorphism in promoter of ATM is associated with longevity. Mech. Ageing. Dev. 131(10), 636–640 (2010). doi:10.1016/j.mad.2010.08.009 PubMedCrossRef

31.

Y.L. Zhou, Association between single nucleotide polymorphisms and radiotherapy sensitivity in esophageal cancer patients. Thesis, Peking Union Medical College (2012)

32.

S.E.Grams, A case-control study of ATM and susceptibility to squamous cell carcinoma of the head and neck, University of Pittsburgh 2007

33.

X. Sole, E. Guino, J. Valls, R. Iniesta, V. Moreno, SNPStats: a web tool for the analysis of association studies. Bioinformatics 22(15), 1928–1929 (2006). doi:10.1093/bioinformatics/btl268 PubMedCrossRef

34.

J. Sekiguchi, D.O. Ferguson, H.T. Chen, E.M. Yang, J. Earle, K. Frank, S. Whitlow, Y.S. Gu, Y. Xu, A. Nussenzweig, F.W. Alt, Genetic interactions between ATM and the nonhomologous end-joining factors in genomic stability and development. Proc. Natl. Acad. Sci. USA 98(6), 3243–3248 (2001). doi:10.1073/pnas.051632098 PubMedCentralPubMedCrossRef

35.

G. Rotman, Y. Shiloh, ATM: from gene to function. Hum. Mol. Genet. 7(10), 1555–1563 (1998). doi:ddb181. [pii]PubMedCrossRef

36.

M.F. Hoekstra, Responses to DNA damage and regulation of cell cycle checkpoints by the ATM protein kinase family. Curr. Opin. Genet. Dev 7(2), 170–175 (1997). doi:S0959-437X(97)80125-6. [pii]PubMedCrossRef

37.

W.K. Kaufmann, R.S. Paules, DNA damage and cell cycle checkpoints. FASEB. J 10(2), 238–247 (1996)PubMed

38.

Amanda G. Paulovich, Leland H.D.P.T. Hartwell, When checkpoints fail. Cell 88(3), 315–321 (1997). doi:10.1016/S0092-8674(00)81870-X PubMedCrossRef

39.

Z.G. Liu, R. Baskaran, E.T. Lea-Chou, L.D. Wood, Y. Chen, M. Karin, J.Y. Wang, Three distinct signalling responses by murine fibroblasts to genotoxic stress. Nature. 384(6606), 273–276 (1996). doi:10.1038/384273a0 PubMedCrossRef

40.

S. Kharbanda, R. Ren, P. Pandey, T.D. Shafman, S.M. Feller, R.R. Weichselbaum, D.W. Kufe, Activation of the c-Abl tyrosine kinase in the stress response to DNA-damaging agents. Nature. 376(6543), 785–788 (1995). doi:10.1038/376785a0 PubMedCrossRef

41.

S.J.D.A. Lee, M.F. Lavin, A. Dritschilo, M. Jung, A novel ionizing radiation-induced signaling pathway that activates the transcription factor NF-kappaB. Oncogene. 17(14), 1821–1826 (1998)PubMedCrossRef

42.

D.P. Gately, J.C. Hittle, G.K. Chan, T.J. Yen, Characterization of ATM expression, localization, and associated DNA-dependent protein kinase activity. Mol. Biol. Cell. 9(9), 2361–2374 (1998)PubMedCentralPubMedCrossRef

43.

Y.C. Taylor, P.G. Duncan, X. Zhang, W.D. Wright, Differences in the DNA supercoiling response of irradiated cell lines from ataxia-telangiectasia versus unaffected individuals. Int. J. Radiat. Biol 59(2), 359–371 (1991). doi:0FRT1BVFQY0RUV3N. [pii]PubMedCrossRef

44.

T.K.H.W. Pandita, Initial chromosome damage but not DNA damage is greater in ataxia telangiectasia cells. Radiat. Res. 130(1), 94–103 (1992)PubMedCrossRef

45.

T.K. Pandita, W.N. Hittelman, The contribution of DNA and chromosome repair deficiencies to the radiosensitivity of ataxia-telangiectasia. Radiat. Res. 131(2), 214–223 (1992)PubMedCrossRef

46.

S. Angele, P. Romestaing, N. Moullan, M. Vuillaume, B. Chapot, M. Friesen, W. Jongmans, D.G. Cox, P. Pisani, J.P. Gerard, J. Hall, ATM haplotypes and cellular response to DNA damage: association with breast cancer risk and clinical radiosensitivity. Cancer. Res. 63(24), 8717–8725 (2003)PubMed

47.

H.C. Wang, W.S. Chang, R.Y. Tsai, C.W. Tsai, L.C. Liu, C.H. Su, H.N. Cheng, Y.A. Tsou, S.S. Sun, C.C. Lin, D.T. Bau, Association between ataxia telangiectasia mutated gene polymorphisms and breast cancer in taiwanese females. Anticancer. Res. 30(12), 5217–5221 (2010)PubMed

48.

D.T. Bau, C.H. Chang, M.H. Tsai, C.F. Chiu, Y.A. Tsou, R.F. Wang, C.W. Tsai, R.Y. Tsai, Association between DNA repair gene ATM polymorphisms and oral cancer susceptibility. Laryngoscope. 120(12), 2417–2422 (2010). doi:10.1002/Lary.21009 PubMedCrossRef

49.

J. Dong, Z. Hu, Y. Shu, S. Pan, W. Chen, Y. Wang, L. Hu, Y. Jiang, J. Dai, H. Ma, G. Jin, H. Shen, Potentially functional polymorphisms in DNA repair genes and non-small-cell lung cancer survival: a pathway-based analysis. Mol. Carcinog. 51(7), 546–552 (2012). doi:10.1002/mc.20819 PubMedCrossRef

50.

H. Edvardsen, T. Tefre, L. Jansen, P. Vu, B.G. Haffty, S.D. Fossa, V.N. Kristensen, A.L. Borresen-Dale, Linkage disequilibrium pattern of the ATM gene in breast cancer patients and controls; association of SNPs and haplotypes to radio-sensitivity and post-lumpectomy local recurrence. Radiat. Oncol. 2, 25 (2007). doi:10.1186/1748-717X-2-25 PubMedCentralPubMedCrossRef

51.

P.E. Bonnen, M.D. Story, C.L. Ashorn, T.A. Buchholz, M.M. Weil, D.L. Nelson, Haplotypes at ATM identify coding-sequence variation and indicate a region of extensive linkage disequilibrium. Am. J. Hum. Genet. 67(6), 1437–1451 (2000). doi:10.1086/316908 PubMedCentralPubMedCrossRef

52.

Y.R. Thorstenson, P.D. Shen, V.G. Tusher, T.L. Wayne, R.W. Davis, G. Chu, P.J. Oefner, Global analysis of ATM polymorphism reveals significant functional constraint. Am. J. Hum. Genet. 69(2), 396–412 (2001). doi:10.1086/321296 PubMedCentralPubMedCrossRef

53.

M. Koren, G. Kimmel, E. Ben-Asher, I. Gal, M.Z. Papa, J.S. Beckmann, D. Lancet, R. Shamir, E. Friedman, ATM haplotypes and breast cancer risk in Jewish high-risk women. Brit. J. Cancer. 94(10), 1537–1543 (2006). doi:10.1038/sj.bjc.6603062 PubMedCentralPubMedCrossRef

Titel: Association of the ATM gene polymorphisms with papillary thyroid cancer
verfasst von: Yulu Gu
Yaqin Yu
Lizhe Ai
Jieping Shi
Xiaoli Liu
Hui Sun
Yawen Liu
Publikationsdatum: 01.04.2014
Verlag: Springer US
Erschienen in: Endocrine / Ausgabe 3/2014
Print ISSN: 1355-008X
Elektronische ISSN: 1559-0100
DOI: https://doi.org/10.1007/s12020-013-0020-1

Leitlinien kompakt für die Innere Medizin

Mit medbee Pocketcards sicher entscheiden.

^{Seit 2022 gehört die medbee GmbH zum Springer Medizin Verlag}

Kostenlos registrieren

Neu im Fachgebiet Innere Medizin

Bei Herzinsuffizienz muss „Eisenmangel“ neu definiert werden!

16.05.2024 Herzinsuffizienz Nachrichten

Bei chronischer Herzinsuffizienz macht es einem internationalen Expertenteam zufolge wenig Sinn, die Diagnose „Eisenmangel“ am Serumferritin festzumachen. Das Team schlägt vor, sich lieber an die Transferrinsättigung zu halten.

Herzinfarkt mit 85 – trotzdem noch intensive Lipidsenkung?

16.05.2024 Hypercholesterinämie Nachrichten

Profitieren nach einem akuten Myokardinfarkt auch Betroffene über 80 Jahre noch von einer intensiven Lipidsenkung zur Sekundärprävention? Um diese Frage zu beantworten, wurden jetzt Registerdaten aus Frankreich ausgewertet.

ADHS-Medikation erhöht das kardiovaskuläre Risiko

16.05.2024 Herzinsuffizienz Nachrichten

Erwachsene, die Medikamente gegen das Aufmerksamkeitsdefizit-Hyperaktivitätssyndrom einnehmen, laufen offenbar erhöhte Gefahr, an Herzschwäche zu erkranken oder einen Schlaganfall zu erleiden. Es scheint eine Dosis-Wirkungs-Beziehung zu bestehen.

Erstmanifestation eines Diabetes-Typ-1 bei Kindern: Ein Notfall!

16.05.2024 DDG-Jahrestagung 2024 Kongressbericht

Manifestiert sich ein Typ-1-Diabetes bei Kindern, ist das ein Notfall – ebenso wie eine diabetische Ketoazidose. Die Grundsäulen der Therapie bestehen aus Rehydratation, Insulin und Kaliumgabe. Insulin ist das Medikament der Wahl zur Behandlung der Ketoazidose.

Update Innere Medizin

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.

Newsletter bestellen

Springer Medizin

Abstract

Bitte loggen Sie sich ein, um Zugang zu diesem Inhalt zu erhalten

Weitere Artikel der Ausgabe 3/2014

Anti-hypertensive treatment in pheochromocytoma and paraganglioma: current management and therapeutic features

Relationships of serum soluble E-selectin concentration with insulin sensitivity and metabolic flexibility in lean and obese women

Non-alcoholic fatty liver disease: a diabetologist’s perspective

The BRAF V600E mutation in papillary thyroid cancer with positive or suspected pre-surgical cytological finding is not associated with advanced stages or worse prognosis

Changes in levels of peripheral hormones controlling appetite are inconsistent with hyperphagia in leptin-deficient subjects