Co-occurrence of myeloproliferative neoplasms and solid tumors is attributed to a synergism between cytoreductive therapy and the common TERT polymorphism rs2736100

Tunde Krahling, Katalin Balassa, Katalin Piroska Kiss, Andras Bors, Arpad Batai, Gabriella Halm, Miklos Egyed, Sandor Fekete, Peter Remenyi, T. Masszi, A. Tordai, H. Andrikovics

Research output: Contribution to journalArticle

12 Citations (Scopus)

Abstract

Background: The germline telomerase reverse transcriptase (TERT) rs2736100-C variant was identified as a susceptibility factor for a variety of solid tumors and recently for myeloproliferative neoplasms (MPN). Methods: LightCycler melting curve analysis was applied to detect risk alleles of TERT rs2736100-C and Janus kinase 2 (JAK2) rs12343867-C tagging 46/1 haplotype in 584 BCR-ABL1-negative MPN, 308 acute, and 86 chronic myeloid leukemia (AML and CML) patients and 400 healthy individuals. Results: TERT rs2736100-C showed an increased allele frequency in BCR-ABL1-negative MPN patients compared with controls (62.7%±2.8% vs. 48.8%±3.5%, P <0.0001) regardless of molecular background or disease type, but not in CML or AML. Combined TERT and JAK2 hetero- or homozygosity conferred even higher risk for classic MPN. Common complications (thrombosis, myelofibrosis, or leukemia) were not associated with the TERT variant; however, adverse survival was noted in TERT variant carrier polycythemia vera patients. MPN patients with the TERT CC genotype had a higher probability (44.4%) to die from solid tumors compared with TERT AC/AA individuals (5.3%; P = 0.004). TERT rs2736100-C carriers had increased risk of solid tumors independently from cytoreductive treatment [3.08 (1.03-9.26), P = 0.045]. Conclusions: TERT rs2736100-C polymorphism predisposes to the development of BCR-ABL1-negative MPN with the cooccurrence of solid tumors, especially with the usage of cytoreductive treatment. Impact: The high frequency of TERT variant in the classic MPN population highlights the importance of the avoidance of long-term cytoreductive treatment in MPN patients.

Original languageEnglish
Pages (from-to)98-104
Number of pages7
JournalCancer Epidemiology Biomarkers and Prevention
Volume25
Issue number1
DOIs
Publication statusPublished - Jan 1 2016

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Telomerase
Neoplasms
Therapeutics
Janus Kinase 2
Polycythemia Vera
Primary Myelofibrosis
Leukemia, Myelogenous, Chronic, BCR-ABL Positive
Gene Frequency
Haplotypes
Freezing
Leukemia
Thrombosis
Alleles
Genotype

ASJC Scopus subject areas

  • Epidemiology
  • Oncology

Cite this

Co-occurrence of myeloproliferative neoplasms and solid tumors is attributed to a synergism between cytoreductive therapy and the common TERT polymorphism rs2736100. / Krahling, Tunde; Balassa, Katalin; Kiss, Katalin Piroska; Bors, Andras; Batai, Arpad; Halm, Gabriella; Egyed, Miklos; Fekete, Sandor; Remenyi, Peter; Masszi, T.; Tordai, A.; Andrikovics, H.

In: Cancer Epidemiology Biomarkers and Prevention, Vol. 25, No. 1, 01.01.2016, p. 98-104.

Research output: Contribution to journalArticle

Krahling, Tunde ; Balassa, Katalin ; Kiss, Katalin Piroska ; Bors, Andras ; Batai, Arpad ; Halm, Gabriella ; Egyed, Miklos ; Fekete, Sandor ; Remenyi, Peter ; Masszi, T. ; Tordai, A. ; Andrikovics, H. / Co-occurrence of myeloproliferative neoplasms and solid tumors is attributed to a synergism between cytoreductive therapy and the common TERT polymorphism rs2736100. In: Cancer Epidemiology Biomarkers and Prevention. 2016 ; Vol. 25, No. 1. pp. 98-104.
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abstract = "Background: The germline telomerase reverse transcriptase (TERT) rs2736100-C variant was identified as a susceptibility factor for a variety of solid tumors and recently for myeloproliferative neoplasms (MPN). Methods: LightCycler melting curve analysis was applied to detect risk alleles of TERT rs2736100-C and Janus kinase 2 (JAK2) rs12343867-C tagging 46/1 haplotype in 584 BCR-ABL1-negative MPN, 308 acute, and 86 chronic myeloid leukemia (AML and CML) patients and 400 healthy individuals. Results: TERT rs2736100-C showed an increased allele frequency in BCR-ABL1-negative MPN patients compared with controls (62.7{\%}±2.8{\%} vs. 48.8{\%}±3.5{\%}, P <0.0001) regardless of molecular background or disease type, but not in CML or AML. Combined TERT and JAK2 hetero- or homozygosity conferred even higher risk for classic MPN. Common complications (thrombosis, myelofibrosis, or leukemia) were not associated with the TERT variant; however, adverse survival was noted in TERT variant carrier polycythemia vera patients. MPN patients with the TERT CC genotype had a higher probability (44.4{\%}) to die from solid tumors compared with TERT AC/AA individuals (5.3{\%}; P = 0.004). TERT rs2736100-C carriers had increased risk of solid tumors independently from cytoreductive treatment [3.08 (1.03-9.26), P = 0.045]. Conclusions: TERT rs2736100-C polymorphism predisposes to the development of BCR-ABL1-negative MPN with the cooccurrence of solid tumors, especially with the usage of cytoreductive treatment. Impact: The high frequency of TERT variant in the classic MPN population highlights the importance of the avoidance of long-term cytoreductive treatment in MPN patients.",
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T1 - Co-occurrence of myeloproliferative neoplasms and solid tumors is attributed to a synergism between cytoreductive therapy and the common TERT polymorphism rs2736100

AU - Krahling, Tunde

AU - Balassa, Katalin

AU - Kiss, Katalin Piroska

AU - Bors, Andras

AU - Batai, Arpad

AU - Halm, Gabriella

AU - Egyed, Miklos

AU - Fekete, Sandor

AU - Remenyi, Peter

AU - Masszi, T.

AU - Tordai, A.

AU - Andrikovics, H.

PY - 2016/1/1

Y1 - 2016/1/1

N2 - Background: The germline telomerase reverse transcriptase (TERT) rs2736100-C variant was identified as a susceptibility factor for a variety of solid tumors and recently for myeloproliferative neoplasms (MPN). Methods: LightCycler melting curve analysis was applied to detect risk alleles of TERT rs2736100-C and Janus kinase 2 (JAK2) rs12343867-C tagging 46/1 haplotype in 584 BCR-ABL1-negative MPN, 308 acute, and 86 chronic myeloid leukemia (AML and CML) patients and 400 healthy individuals. Results: TERT rs2736100-C showed an increased allele frequency in BCR-ABL1-negative MPN patients compared with controls (62.7%±2.8% vs. 48.8%±3.5%, P <0.0001) regardless of molecular background or disease type, but not in CML or AML. Combined TERT and JAK2 hetero- or homozygosity conferred even higher risk for classic MPN. Common complications (thrombosis, myelofibrosis, or leukemia) were not associated with the TERT variant; however, adverse survival was noted in TERT variant carrier polycythemia vera patients. MPN patients with the TERT CC genotype had a higher probability (44.4%) to die from solid tumors compared with TERT AC/AA individuals (5.3%; P = 0.004). TERT rs2736100-C carriers had increased risk of solid tumors independently from cytoreductive treatment [3.08 (1.03-9.26), P = 0.045]. Conclusions: TERT rs2736100-C polymorphism predisposes to the development of BCR-ABL1-negative MPN with the cooccurrence of solid tumors, especially with the usage of cytoreductive treatment. Impact: The high frequency of TERT variant in the classic MPN population highlights the importance of the avoidance of long-term cytoreductive treatment in MPN patients.

AB - Background: The germline telomerase reverse transcriptase (TERT) rs2736100-C variant was identified as a susceptibility factor for a variety of solid tumors and recently for myeloproliferative neoplasms (MPN). Methods: LightCycler melting curve analysis was applied to detect risk alleles of TERT rs2736100-C and Janus kinase 2 (JAK2) rs12343867-C tagging 46/1 haplotype in 584 BCR-ABL1-negative MPN, 308 acute, and 86 chronic myeloid leukemia (AML and CML) patients and 400 healthy individuals. Results: TERT rs2736100-C showed an increased allele frequency in BCR-ABL1-negative MPN patients compared with controls (62.7%±2.8% vs. 48.8%±3.5%, P <0.0001) regardless of molecular background or disease type, but not in CML or AML. Combined TERT and JAK2 hetero- or homozygosity conferred even higher risk for classic MPN. Common complications (thrombosis, myelofibrosis, or leukemia) were not associated with the TERT variant; however, adverse survival was noted in TERT variant carrier polycythemia vera patients. MPN patients with the TERT CC genotype had a higher probability (44.4%) to die from solid tumors compared with TERT AC/AA individuals (5.3%; P = 0.004). TERT rs2736100-C carriers had increased risk of solid tumors independently from cytoreductive treatment [3.08 (1.03-9.26), P = 0.045]. Conclusions: TERT rs2736100-C polymorphism predisposes to the development of BCR-ABL1-negative MPN with the cooccurrence of solid tumors, especially with the usage of cytoreductive treatment. Impact: The high frequency of TERT variant in the classic MPN population highlights the importance of the avoidance of long-term cytoreductive treatment in MPN patients.

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