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@article{Watts:2021:10.1002/ijc.33416,
author = {Watts, EL and Fensom, GK and Byrne, KS and Perez-Cornago, A and Allen, NE and Knuppel, A and Gunter, MJ and Holmes, M and Martin, RM and Murphy, N and Tsilidis, KK and Yeap, BB and Key, TJ and Travis, RC},
doi = {10.1002/ijc.33416},
journal = {International Journal of Cancer},
pages = {2274--2288},
title = {Circulating insulin-like growth factor-I, total and free testosterone concentrations and prostate cancer risk in 200 000 men in UK Biobank},
url = {http://dx.doi.org/10.1002/ijc.33416},
volume = {148},
year = {2021}
}

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TY  - JOUR
AB  - Insulinlike growth factorI (IGFI) and testosterone have been implicated in prostate cancer aetiology. Using data from a large prospective fullcohort with standardised assays and repeat blood measurements, and genetic data from an international consortium, we investigated the associations of circulating IGFI, sex hormonebinding globulin (SHBG), and total and calculated free testosterone concentrations with prostate cancer incidence and mortality. For prospective analyses, risk was estimated using multivariableadjusted Cox regression in 199 698 male UK Biobank participants. Hazard ratios (HRs) were corrected for regression dilution bias using repeat hormone measurements from a subsample. Twosample Mendelian randomisation (MR) analysis of IGFI and risk used genetic instruments identified from UK Biobank men and genetic outcome data from the PRACTICAL consortium (79 148 cases and 61 106 controls). We used cis and all (cis and trans) SNP MR approaches. A total of 5402 men were diagnosed with and 295 died from prostate cancer (mean followup 6.9 years). Higher circulating IGFI was associated with elevated prostate cancer diagnosis (HR per 5 nmol/L increment = 1.09, 95% CI 1.051.12) and mortality (HR per 5 nmol/L increment = 1.15, 1.021.29). MR analyses also supported the role of IGFI in prostate cancer diagnosis (cisMR odds ratio per 5 nmol/L increment = 1.34, 1.071.68). In observational analyses, higher free testosterone was associated with a higher risk of prostate cancer (HR per 50 pmol/L increment = 1.10, 1.051.15). Higher SHBG was associated with a lower risk (HR per 10 nmol/L increment = 0.95, 0.940.97), neither was associated with prostate cancer mortality. Total testosterone was not associated with prostate cancer. These findings implicate IGFI and free testosterone in prostate cancer development and/or progression.
AU  - Watts,EL
AU  - Fensom,GK
AU  - Byrne,KS
AU  - Perez-Cornago,A
AU  - Allen,NE
AU  - Knuppel,A
AU  - Gunter,MJ
AU  - Holmes,M
AU  - Martin,RM
AU  - Murphy,N
AU  - Tsilidis,KK
AU  - Yeap,BB
AU  - Key,TJ
AU  - Travis,RC
DO  - 10.1002/ijc.33416
EP  - 2288
PY  - 2021///
SN  - 0020-7136
SP  - 2274
TI  - Circulating insulin-like growth factor-I, total and free testosterone concentrations and prostate cancer risk in 200 000 men in UK Biobank
T2  - International Journal of Cancer
UR  - http://dx.doi.org/10.1002/ijc.33416
UR  - http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000597566200001&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=1ba7043ffcc86c417c072aa74d649202
UR  - https://onlinelibrary.wiley.com/doi/10.1002/ijc.33416
UR  - http://hdl.handle.net/10044/1/85753
VL  - 148
ER  -

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