ORCID Profile
0000-0003-2294-307X
Current Organisation
University of Oxford
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Publisher: American Association for Cancer Research (AACR)
Date: 31-03-2023
DOI: 10.1158/0008-5472.22421475
Abstract: Supplementary methods, tables and figures
Publisher: American Association for Cancer Research (AACR)
Date: 09-2020
DOI: 10.1158/1055-9965.EPI-19-1527
Abstract: A polygenic hazard score (PHS), the weighted sum of 54 SNP genotypes, was previously validated for association with clinically significant prostate cancer and for improved prostate cancer screening accuracy. Here, we assess the potential impact of PHS-informed screening. United Kingdom population incidence data (Cancer Research United Kingdom) and data from the Cluster Randomized Trial of PSA Testing for Prostate Cancer were combined to estimate age-specific clinically significant prostate cancer incidence (Gleason score ≥7, stage T3–T4, PSA ≥10, or nodal/distant metastases). Using HRs estimated from the ProtecT prostate cancer trial, age-specific incidence rates were calculated for various PHS risk percentiles. Risk-equivalent age, when someone with a given PHS percentile has prostate cancer risk equivalent to an average 50-year-old man (50-year-standard risk), was derived from PHS and incidence data. Positive predictive value (PPV) of PSA testing for clinically significant prostate cancer was calculated using PHS-adjusted age groups. The expected age at diagnosis of clinically significant prostate cancer differs by 19 years between the 1st and 99th PHS percentiles: men with PHS in the 1st and 99th percentiles reach the 50-year-standard risk level at ages 60 and 41, respectively. PPV of PSA was higher for men with higher PHS-adjusted age. PHS provides in idualized estimates of risk-equivalent age for clinically significant prostate cancer. Screening initiation could be adjusted by a man's PHS. Personalized genetic risk assessments could inform prostate cancer screening decisions.
Publisher: Cold Spring Harbor Laboratory
Date: 16-08-2023
DOI: 10.1101/2023.08.14.23294084
Abstract: Circulating proteins are integral to many biological processes. We aimed to assess differences in the plasma proteome between people of different dietary groups defined by degree of animal food consumption. The UK Biobank recruited middle-aged adults (mostly 40 to 69 years) throughout the UK between 2006-2010. Relative concentrations of 1463 plasma proteins were quantified using the Olink Proximity Extension Assay on blood s les from 49,326 participants, who were also asked to report their ethnicity and consumption of red and processed meat, poultry, fish, dairy and eggs. We defined six diet groups among the white British participants (23,116 regular meat eaters, 23,323 low meat eaters, 484 poultry eaters, 1074 fish eaters, 722 vegetarians, and 54 vegans), and two diet groups among the British Indians (390 meat eaters and 163 vegetarians). We used multivariable-adjusted linear regressions to assess differences in protein concentrations between diet groups, with correction for multiple testing. We observed significant differences in many plasma proteins by diet group (683 proteins in white British participants, 1 in British Indians), in particular many proteins that are majority expressed in the digestive system. Of the biggest differences, compared with regular meat eaters, the non-meat eaters had significantly higher FGF21 (e.g. +0.40 SD in vegetarians), GUCA2A (+0.33), FOLR1 (+0.32), IGFBP2 (+0.31) and DSG2 (+0.30) all groups except the vegans had lower HAVCR1 (-0.38 in vegetarians). The observed differences were generally similar in direction in both ethnicities. In this first comprehensive assessment of plasma proteins by diet group, we identified many differences in proteins between groups defined by animal food consumption this variation in protein levels suggests differences in various biological activities, including gastrointestinal tract and kidney function, which may relate to differences in future disease risk.
Publisher: American Association for Cancer Research (AACR)
Date: 31-03-2023
DOI: 10.1158/0008-5472.22421475.V1
Abstract: Supplementary methods, tables and figures
Publisher: American Association for Cancer Research (AACR)
Date: 04-04-2019
Publisher: Oxford University Press (OUP)
Date: 03-10-2020
DOI: 10.1093/JNCI/DJAA154
Abstract: In the era of widespread prostate-specific antigen testing, it is important to focus etiologic research on the outcome of aggressive prostate cancer, but studies have defined this outcome differently. We aimed to develop an evidence-based consensus definition of aggressive prostate cancer using clinical features at diagnosis for etiologic epidemiologic research. Among prostate cancer cases diagnosed in 2007 in the National Cancer Institute’s Surveillance, Epidemiology, and End Results-18 database with follow-up through 2017, we compared the performance of categorizations of aggressive prostate cancer in discriminating fatal prostate cancer within 10 years of diagnosis, placing the most emphasis on sensitivity and positive predictive value (PPV). In our case population (n = 55 900), 3073 men died of prostate cancer within 10 years. Among 12 definitions that included TNM staging and Gleason score, sensitivities ranged from 0.64 to 0.89 and PPVs ranged from 0.09 to 0.23. We propose defining aggressive prostate cancer as diagnosis of category T4 or N1 or M1 or Gleason score of 8 or greater prostate cancer, because this definition had one of the higher PPVs (0.23, 95% confidence interval = 0.22 to 0.24) and reasonable sensitivity (0.66, 95% confidence interval = 0.64 to 0.67) for prostate cancer death within 10 years. Results were similar across sensitivity analyses. We recommend that etiologic epidemiologic studies of prostate cancer report results for this definition of aggressive prostate cancer. We also recommend that studies separately report results for advanced category (T4 or N1 or M1), high-grade (Gleason score ≥8), and fatal prostate cancer. Use of this comprehensive set of endpoints will facilitate comparison of results from different studies and help elucidate prostate cancer etiology.
Publisher: American Association for Cancer Research (AACR)
Date: 31-03-2023
DOI: 10.1158/0008-5472.C.6510939
Abstract: Abstract Previous prospective studies assessing the relationship between circulating concentrations of vitamin D and prostate cancer risk have shown inconclusive results, particularly for risk of aggressive disease. In this study, we examine the association between prediagnostic concentrations of 25-hydroxyvitamin D [25(OH)D] and 1,25-dihydroxyvitamin D [1,25(OH) sub /sub D] and the risk of prostate cancer overall and by tumor characteristics. Principal investigators of 19 prospective studies provided in idual participant data on circulating 25(OH)D and 1,25(OH) sub /sub D for up to 13,462 men with incident prostate cancer and 20,261 control participants. ORs for prostate cancer by study-specific fifths of season-standardized vitamin D concentration were estimated using multivariable-adjusted conditional logistic regression. 25(OH)D concentration was positively associated with risk for total prostate cancer (multivariable-adjusted OR comparing highest vs. lowest study-specific fifth was 1.22 95% confidence interval, 1.13–1.31 i P /i trend 0.001). However, this association varied by disease aggressiveness ( i P /i sub heterogeneity /sub = 0.014) higher circulating 25(OH)D was associated with a higher risk of nonaggressive disease (OR per 80 percentile increase = 1.24, 1.13–1.36) but not with aggressive disease (defined as stage 4, metastases, or prostate cancer death, 0.95, 0.78–1.15). 1,25(OH) sub /sub D concentration was not associated with risk for prostate cancer overall or by tumor characteristics. The absence of an association of vitamin D with aggressive disease does not support the hypothesis that vitamin D deficiency increases prostate cancer risk. Rather, the association of high circulating 25(OH)D concentration with a higher risk of nonaggressive prostate cancer may be influenced by detection bias. Significance: This international collaboration comprises the largest prospective study on blood vitamin D and prostate cancer risk and shows no association with aggressive disease but some evidence of a higher risk of nonaggressive disease. /
Publisher: American Association for Cancer Research (AACR)
Date: 31-03-2023
DOI: 10.1158/0008-5472.C.6510939.V1
Abstract: Abstract Previous prospective studies assessing the relationship between circulating concentrations of vitamin D and prostate cancer risk have shown inconclusive results, particularly for risk of aggressive disease. In this study, we examine the association between prediagnostic concentrations of 25-hydroxyvitamin D [25(OH)D] and 1,25-dihydroxyvitamin D [1,25(OH) sub /sub D] and the risk of prostate cancer overall and by tumor characteristics. Principal investigators of 19 prospective studies provided in idual participant data on circulating 25(OH)D and 1,25(OH) sub /sub D for up to 13,462 men with incident prostate cancer and 20,261 control participants. ORs for prostate cancer by study-specific fifths of season-standardized vitamin D concentration were estimated using multivariable-adjusted conditional logistic regression. 25(OH)D concentration was positively associated with risk for total prostate cancer (multivariable-adjusted OR comparing highest vs. lowest study-specific fifth was 1.22 95% confidence interval, 1.13–1.31 i P /i trend 0.001). However, this association varied by disease aggressiveness ( i P /i sub heterogeneity /sub = 0.014) higher circulating 25(OH)D was associated with a higher risk of nonaggressive disease (OR per 80 percentile increase = 1.24, 1.13–1.36) but not with aggressive disease (defined as stage 4, metastases, or prostate cancer death, 0.95, 0.78–1.15). 1,25(OH) sub /sub D concentration was not associated with risk for prostate cancer overall or by tumor characteristics. The absence of an association of vitamin D with aggressive disease does not support the hypothesis that vitamin D deficiency increases prostate cancer risk. Rather, the association of high circulating 25(OH)D concentration with a higher risk of nonaggressive prostate cancer may be influenced by detection bias. Significance: This international collaboration comprises the largest prospective study on blood vitamin D and prostate cancer risk and shows no association with aggressive disease but some evidence of a higher risk of nonaggressive disease. /
Publisher: Elsevier BV
Date: 08-2019
DOI: 10.1093/AJCN/NQZ072
Publisher: Elsevier BV
Date: 06-2019
DOI: 10.1093/JN/NXZ031
Publisher: American Association for Cancer Research (AACR)
Date: 2019
DOI: 10.1158/0008-5472.CAN-18-2318
Abstract: This international collaboration comprises the largest prospective study on blood vitamin D and prostate cancer risk and shows no association with aggressive disease but some evidence of a higher risk of nonaggressive disease.
Location: United Kingdom of Great Britain and Northern Ireland
No related grants have been discovered for Timothy Key.