Gene Polymorphism of Xenobiotic Biotransformation Enzymes in Patients with Classical Ph-Negative Myeloproliferative Neoplasms

Ovsepyan, V. A.; Tregubova, E. V.; Лучинин, А. С.; Minaeva, Natalia

doi:10.1007/s10517-019-04619-5

Cited by 5 publications

(1 citation statement)

References 13 publications

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“…Moreover, there are several evidences for a causative role of somatic mutations in MPN development, such as the V617F mutation in the JAK2 gene and mutations in CALR and MPL 6,7 . In addition, common low penetrance variants have been associated with the disease risk, in particular, seven single nucleotide polymorphisms (SNPs) have been identified through three genome-wide association studies (GWAS) 6,8,9 and, through case-control studies, additional hits such as the 46/1 JAK2 haplotype 10 and several SNPs belonging to genes involved in DNA repair, apoptosis, inflammation, and detoxification [11][12][13][14][15][16] .…”

Section: Introductionmentioning

confidence: 99%

Genetic polymorphisms associated with telomere length and risk of developing myeloproliferative neoplasms

et al. 2020

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Telomere length measured in leukocyte (LTL) has been found to be associated with the risk of developing several cancer types, including myeloproliferative neoplasms (MPNs). LTL is genetically determined by, at least, 11 SNPs previously shown to influence LTL. Their combination in a score has been used as a genetic instrument to measure LTL and evaluate the causative association between LTL and the risk of several cancer types. We tested, for the first time, the "teloscore" in 480 MPN patients and 909 healthy controls in a European multi-center case-control study. We found an increased risk to develop MPNs with longer genetically determined telomeres (OR = 1.82, 95% CI 1.24-2.68, P = 2.21 × 10 −3 , comparing the highest with the lowest quintile of the teloscore distribution). Analyzing the SNPs individually we confirm the association between TERT-rs2736100-C allele and increased risk of developing MPNs and we report a novel association of the OBFC1-rs9420907-C variant with higher MPN risk (OR allelic = 1.43; 95% CI 1.15-1.77; P = 1.35 × 10 −3). Consistently with the results obtained with the teloscore, both risk alleles are also associated with longer LTL. In conclusion, our results suggest that genetically determined longer telomeres could be a risk marker for MPN development.

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