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Plasma Urate, Cancer Incidence, and All-Cause Mortality: A Mendelian Randomization Study

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@article{2277cc21e01740569481463c9f81a4bf,
title = "Plasma Urate, Cancer Incidence, and All-Cause Mortality: A Mendelian Randomization Study",
abstract = "BACKGROUND: Observationally, high plasma urate is associated with high risk of cancer. We used a Mendelian randomization design to test the hypothesis that high concentrations of plasma urate are associated with high cancer incidence and all-cause mortality observationally and genetically.METHODS: We performed observational and genetic analyses using plasma urate and the urate solute carrier family 2 member 9 (SLC2A9) rs7442295 genotype in 86210 individuals from the Copenhagen General Population Study. Cancer and mortality end points were from national cancer and death registries. Incidences and risk of cancer and all-cause mortality were calculated using Cox regression, Fine and Gray competing-risks regression, and instrumental variable analyses.RESULTS: During a median follow-up time of 3.9 years for cancer and 4.9 years for all-cause mortality, 3243 individuals received a diagnosis of cancer and 3978 died. Observationally, 50{\%} higher plasma urate was associated with multivariable-adjusted hazard ratios of 1.11 (95{\%} CI, 1.05-1.18) for cancer incidence and 1.07 (1.01-1.13) for all-cause mortality. Each A-allele of the SLC2A9 rs7442295 was associated with 9{\%} higher plasma urate and hazard ratios of 1.07 (1.01-1.14) for cancer incidence and 1.07 (1.02-1.13) for all-cause mortality. In instrumental variable analyses, the odds ratios for a genetically determined 50{\%} higher plasma urate was 1.22 (1.02-1.47) for cancer incidence and 1.49 (1.13-1.93) for all-cause mortality.CONCLUSIONS: High plasma urate was both observationally and genetically associated with high cancer incidence and high all-cause mortality, suggesting causal relationships.",
keywords = "Adult, Aged, Aged, 80 and over, Alleles, Cause of Death, Genotype, Glucose Transport Proteins, Facilitative, Humans, Middle Aged, Neoplasms, Risk Factors, Survival Analysis, Uric Acid, Young Adult, Journal Article, Observational Study, Randomized Controlled Trial",
author = "Kobylecki, {Camilla J} and Shoaib Afzal and Nordestgaard, {B{\o}rge G}",
note = "{\circledC} 2017 American Association for Clinical Chemistry.",
year = "2017",
month = "6",
doi = "10.1373/clinchem.2016.268185",
language = "English",
volume = "63",
pages = "1151--1160",
journal = "Clinical Chemistry",
issn = "0009-9147",
publisher = "American Association for Clinical Chemistry, Inc",
number = "6",

}

RIS

TY - JOUR

T1 - Plasma Urate, Cancer Incidence, and All-Cause Mortality

T2 - A Mendelian Randomization Study

AU - Kobylecki, Camilla J

AU - Afzal, Shoaib

AU - Nordestgaard, Børge G

N1 - © 2017 American Association for Clinical Chemistry.

PY - 2017/6

Y1 - 2017/6

N2 - BACKGROUND: Observationally, high plasma urate is associated with high risk of cancer. We used a Mendelian randomization design to test the hypothesis that high concentrations of plasma urate are associated with high cancer incidence and all-cause mortality observationally and genetically.METHODS: We performed observational and genetic analyses using plasma urate and the urate solute carrier family 2 member 9 (SLC2A9) rs7442295 genotype in 86210 individuals from the Copenhagen General Population Study. Cancer and mortality end points were from national cancer and death registries. Incidences and risk of cancer and all-cause mortality were calculated using Cox regression, Fine and Gray competing-risks regression, and instrumental variable analyses.RESULTS: During a median follow-up time of 3.9 years for cancer and 4.9 years for all-cause mortality, 3243 individuals received a diagnosis of cancer and 3978 died. Observationally, 50% higher plasma urate was associated with multivariable-adjusted hazard ratios of 1.11 (95% CI, 1.05-1.18) for cancer incidence and 1.07 (1.01-1.13) for all-cause mortality. Each A-allele of the SLC2A9 rs7442295 was associated with 9% higher plasma urate and hazard ratios of 1.07 (1.01-1.14) for cancer incidence and 1.07 (1.02-1.13) for all-cause mortality. In instrumental variable analyses, the odds ratios for a genetically determined 50% higher plasma urate was 1.22 (1.02-1.47) for cancer incidence and 1.49 (1.13-1.93) for all-cause mortality.CONCLUSIONS: High plasma urate was both observationally and genetically associated with high cancer incidence and high all-cause mortality, suggesting causal relationships.

AB - BACKGROUND: Observationally, high plasma urate is associated with high risk of cancer. We used a Mendelian randomization design to test the hypothesis that high concentrations of plasma urate are associated with high cancer incidence and all-cause mortality observationally and genetically.METHODS: We performed observational and genetic analyses using plasma urate and the urate solute carrier family 2 member 9 (SLC2A9) rs7442295 genotype in 86210 individuals from the Copenhagen General Population Study. Cancer and mortality end points were from national cancer and death registries. Incidences and risk of cancer and all-cause mortality were calculated using Cox regression, Fine and Gray competing-risks regression, and instrumental variable analyses.RESULTS: During a median follow-up time of 3.9 years for cancer and 4.9 years for all-cause mortality, 3243 individuals received a diagnosis of cancer and 3978 died. Observationally, 50% higher plasma urate was associated with multivariable-adjusted hazard ratios of 1.11 (95% CI, 1.05-1.18) for cancer incidence and 1.07 (1.01-1.13) for all-cause mortality. Each A-allele of the SLC2A9 rs7442295 was associated with 9% higher plasma urate and hazard ratios of 1.07 (1.01-1.14) for cancer incidence and 1.07 (1.02-1.13) for all-cause mortality. In instrumental variable analyses, the odds ratios for a genetically determined 50% higher plasma urate was 1.22 (1.02-1.47) for cancer incidence and 1.49 (1.13-1.93) for all-cause mortality.CONCLUSIONS: High plasma urate was both observationally and genetically associated with high cancer incidence and high all-cause mortality, suggesting causal relationships.

KW - Adult

KW - Aged

KW - Aged, 80 and over

KW - Alleles

KW - Cause of Death

KW - Genotype

KW - Glucose Transport Proteins, Facilitative

KW - Humans

KW - Middle Aged

KW - Neoplasms

KW - Risk Factors

KW - Survival Analysis

KW - Uric Acid

KW - Young Adult

KW - Journal Article

KW - Observational Study

KW - Randomized Controlled Trial

U2 - 10.1373/clinchem.2016.268185

DO - 10.1373/clinchem.2016.268185

M3 - Journal article

VL - 63

SP - 1151

EP - 1160

JO - Clinical Chemistry

JF - Clinical Chemistry

SN - 0009-9147

IS - 6

ER -

ID: 52335831