In:
Cancer Epidemiology, Biomarkers & Prevention, American Association for Cancer Research (AACR), Vol. 25, No. 1 ( 2016-01-01), p. 98-104
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 & lt; 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 co-occurrence 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. Cancer Epidemiol Biomarkers Prev; 25(1); 98–104. ©2015 AACR.
Type of Medium:
Online Resource
ISSN:
1055-9965
,
1538-7755
DOI:
10.1158/1055-9965.EPI-15-0805
Language:
English
Publisher:
American Association for Cancer Research (AACR)
Publication Date:
2016
detail.hit.zdb_id:
2036781-8
detail.hit.zdb_id:
1153420-5
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