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Measured and genetically predicted plasma YKL-40 levels and melanoma mortality

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@article{bec34e59c7b8450f933841acceb5a605,
title = "Measured and genetically predicted plasma YKL-40 levels and melanoma mortality",
abstract = "PURPOSE: High plasma levels of YKL-40 might be associated with mortality in patients with melanoma, and it is unknown if YKL-40 is causally related to mortality.EXPERIMENTAL DESIGN: We studied two cohorts: 2618 patients with melanoma from hospital clinics and 1413 general population patients with melanoma, totalling 4031 patients followed up for mortality end-points for up to 20 years. All were genotyped for CHI3L1 rs4950928, highly predictive of lifelong plasma YKL-40, and plasma YKL-40 levels were measured in 2165 patients. We tested the hypotheses that measured and genetically predicted high plasma YKL-40 are associated with increased mortality in patients with melanoma.RESULTS: For the hospital melanoma cohort, age- and sex-adjusted hazard ratios for death in individuals with measured plasma YKL-40 in the 96-100th percentile versus 1-95th percentile and per 10-percentile increase were 1.52 (95{\%} confidence interval, 1.07-2.16) and 1.07 (1.02-1.11), respectively, most pronounced for patients with localised melanomas. Each C-allele of the CHI3L1 rs4950928 genotype was associated with plasma YKL-40 level increases of 32{\%} in the hospital melanoma cohort (p = 6 × 10-48) and 43{\%} in the general population melanoma cohort (p = 7 × 10-13). Multifactorially adjusted ratios for these increases in the combined cohorts were 1.04 (1.00-1.09) observationally for measured plasma YKL-40 and 0.98 (0.86-1.12) for the genetically predicted plasma YKL-40.CONCLUSION: Measured, but not genetically predicted, increasing plasma YKL-40 was associated with increased mortality in patients with melanoma. Plasma YKL-40 is a marker but less likely to be a cause of increased mortality in patients with melanoma.",
author = "Hafsa Ismail and Jens Helby and H{\"o}lmich, {Lisbet R} and Chakera, {Annette H} and Lars Bastholt and Helle Klyver and Pia Sj{\o}gren and Henrik Schmidt and Liv Sch{\"o}llhammer and Johansen, {Julia S} and Nordestgaard, {B{\o}rge G} and Bojesen, {Stig E}",
note = "Copyright {\circledC} 2019 Elsevier Ltd. All rights reserved.",
year = "2019",
month = "11",
doi = "10.1016/j.ejca.2019.08.025",
language = "English",
volume = "121",
pages = "74--84",
journal = "European Journal of Cancer, Supplement",
issn = "0959-8049",
publisher = "Pergamon",

}

RIS

TY - JOUR

T1 - Measured and genetically predicted plasma YKL-40 levels and melanoma mortality

AU - Ismail, Hafsa

AU - Helby, Jens

AU - Hölmich, Lisbet R

AU - Chakera, Annette H

AU - Bastholt, Lars

AU - Klyver, Helle

AU - Sjøgren, Pia

AU - Schmidt, Henrik

AU - Schöllhammer, Liv

AU - Johansen, Julia S

AU - Nordestgaard, Børge G

AU - Bojesen, Stig E

N1 - Copyright © 2019 Elsevier Ltd. All rights reserved.

PY - 2019/11

Y1 - 2019/11

N2 - PURPOSE: High plasma levels of YKL-40 might be associated with mortality in patients with melanoma, and it is unknown if YKL-40 is causally related to mortality.EXPERIMENTAL DESIGN: We studied two cohorts: 2618 patients with melanoma from hospital clinics and 1413 general population patients with melanoma, totalling 4031 patients followed up for mortality end-points for up to 20 years. All were genotyped for CHI3L1 rs4950928, highly predictive of lifelong plasma YKL-40, and plasma YKL-40 levels were measured in 2165 patients. We tested the hypotheses that measured and genetically predicted high plasma YKL-40 are associated with increased mortality in patients with melanoma.RESULTS: For the hospital melanoma cohort, age- and sex-adjusted hazard ratios for death in individuals with measured plasma YKL-40 in the 96-100th percentile versus 1-95th percentile and per 10-percentile increase were 1.52 (95% confidence interval, 1.07-2.16) and 1.07 (1.02-1.11), respectively, most pronounced for patients with localised melanomas. Each C-allele of the CHI3L1 rs4950928 genotype was associated with plasma YKL-40 level increases of 32% in the hospital melanoma cohort (p = 6 × 10-48) and 43% in the general population melanoma cohort (p = 7 × 10-13). Multifactorially adjusted ratios for these increases in the combined cohorts were 1.04 (1.00-1.09) observationally for measured plasma YKL-40 and 0.98 (0.86-1.12) for the genetically predicted plasma YKL-40.CONCLUSION: Measured, but not genetically predicted, increasing plasma YKL-40 was associated with increased mortality in patients with melanoma. Plasma YKL-40 is a marker but less likely to be a cause of increased mortality in patients with melanoma.

AB - PURPOSE: High plasma levels of YKL-40 might be associated with mortality in patients with melanoma, and it is unknown if YKL-40 is causally related to mortality.EXPERIMENTAL DESIGN: We studied two cohorts: 2618 patients with melanoma from hospital clinics and 1413 general population patients with melanoma, totalling 4031 patients followed up for mortality end-points for up to 20 years. All were genotyped for CHI3L1 rs4950928, highly predictive of lifelong plasma YKL-40, and plasma YKL-40 levels were measured in 2165 patients. We tested the hypotheses that measured and genetically predicted high plasma YKL-40 are associated with increased mortality in patients with melanoma.RESULTS: For the hospital melanoma cohort, age- and sex-adjusted hazard ratios for death in individuals with measured plasma YKL-40 in the 96-100th percentile versus 1-95th percentile and per 10-percentile increase were 1.52 (95% confidence interval, 1.07-2.16) and 1.07 (1.02-1.11), respectively, most pronounced for patients with localised melanomas. Each C-allele of the CHI3L1 rs4950928 genotype was associated with plasma YKL-40 level increases of 32% in the hospital melanoma cohort (p = 6 × 10-48) and 43% in the general population melanoma cohort (p = 7 × 10-13). Multifactorially adjusted ratios for these increases in the combined cohorts were 1.04 (1.00-1.09) observationally for measured plasma YKL-40 and 0.98 (0.86-1.12) for the genetically predicted plasma YKL-40.CONCLUSION: Measured, but not genetically predicted, increasing plasma YKL-40 was associated with increased mortality in patients with melanoma. Plasma YKL-40 is a marker but less likely to be a cause of increased mortality in patients with melanoma.

U2 - 10.1016/j.ejca.2019.08.025

DO - 10.1016/j.ejca.2019.08.025

M3 - Journal article

VL - 121

SP - 74

EP - 84

JO - European Journal of Cancer, Supplement

JF - European Journal of Cancer, Supplement

SN - 0959-8049

ER -

ID: 59139599