Genetic predisposition to metabolically unfavourable adiposity and prostate cancer risk: A Mendelian randomization analysis

Aurora Perez-Cornago; Karl Smith-Byrne; Emma Hazelwood; Cody Z. Watling; Susan Martin; Timothy Frayling; Sarah J Lewis; Richard M Martin; Hanieh Yaghootkar; Ruth C.  Travis; Timothy J.  Key

doi:10.1002/cam4.6220

Genetic predisposition to metabolically unfavourable adiposity and prostate cancer risk: A Mendelian randomization analysis

Aurora Perez-Cornago^*, Karl Smith-Byrne, Emma Hazelwood, Cody Z. Watling, Susan Martin, Timothy Frayling, Sarah J Lewis, Richard M Martin, Hanieh Yaghootkar, Ruth C. Travis , Timothy J. Key

^*Corresponding author for this work

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Abstract

Background: The associations of adiposity with aggressive prostate cancer risk are unclear. Using two-sample Mendelian randomization, we assessed the association of metabolically unfavourable adiposity (UFA), favourable adiposity (FA) and for comparison body mass index (BMI), with prostate cancer, including aggressive prostate cancer.

Methods: We examined the association of these genetically predicted adiposity-related traits with risk of prostate cancer overall, aggressive and early onset disease using outcome summary statistics from the PRACTICAL consortium (including 15,167 aggressive cases).

Results: In inverse-variance weighted models, there was little evidence that genetically predicted one standard deviation higher UFA, FA and BMI were associated with aggressive prostate cancer [OR: 0.85 (95% CI:0.61-1.19), 0.80 (0.53-1.23) and 0.97 (0.88-1.08), respectively]; these associations were largely consistent in sensitivity analyses accounting for horizontal pleiotropy. There was no strong evidence that genetically determined UFA, FA or BMI were associated with overall prostate cancer or early age of onset prostate cancer.

Conclusions: We did not find differences in the associations of UFA and FA with prostate cancer risk, which suggest that adiposity is unlikely to influence prostate cancer via the metabolic factors assessed; however, these did not cover some aspects related to metabolic health that may link obesity with aggressive prostate cancer, which should be explored in future studies.

Original language	English
Pages (from-to)	16482-16489
Number of pages	8
Journal	Cancer Medicine
Volume	12
Issue number	15
Early online date	12 Jun 2023
DOIs	https://doi.org/10.1002/cam4.6220
Publication status	E-pub ahead of print - 12 Jun 2023

Bibliographical note

Funding Information:
This research was funded by Cancer Research UK Population Research Fellowship number C60192/A28516 to APC. APC is also supported by the World Cancer Research Fund (WCRF UK), as part of the Word Cancer Research Fund International grant programme (2019/1953). KS‐M, RT and TJK are supported by Cancer Research UK (C8221/A29017). EH is supported by a Cancer Research UK Population Research Committee Studentship (C18281/A30905). RMM is a National Institute for Health Research Senior Investigator (NIHR202411). EH, RMM and SJL are supported by a Cancer Research UK 25 (C18281/A29019) programme grant (the Integrative Cancer Epidemiology Programme). RMM is also supported by the NIHR Bristol Biomedical Research Centre which is funded by the NIHR (BRC‐1215‐20011) and is a partnership between University Hospitals Bristol and Weston NHS Foundation Trust and the University of Bristol. RMM and EH are affiliated with the Medical Research Council Integrative Epidemiology Unit at the University of Bristol which is supported by the Medical Research Council (MC_UU_00011/1, MC_UU_00011/3, MC_UU_00011/6 and MC_UU_00011/4) and the University of Bristol. Department of Health and Social Care disclaimer: The views expressed are those of the author(s) and not necessarily those of the NHS, the NIHR or the Department of Health and Social Care. SM is supported by an ‘Expanding excellence in England’ award from Research England and by the National Institute for Health and Care Research Exeter Biomedical Research Centre.

Publisher Copyright:
© 2023 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.

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8074 (C18281/A29019) ICEP2 - Programme Award: Towards improved casual evidence and enhanced prediction of cancer risk and survival
Martin, R. M.
1/10/20 → 30/09/25
Project: Research

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Perez-Cornago, A., Smith-Byrne, K., Hazelwood, E., Watling, C. Z., Martin, S., Frayling, T., Lewis, S. J., Martin, R. M., Yaghootkar, H., Travis , R. C., & Key , T. J. (2023). Genetic predisposition to metabolically unfavourable adiposity and prostate cancer risk: A Mendelian randomization analysis. Cancer Medicine, 12(15), 16482-16489. Advance online publication. https://doi.org/10.1002/cam4.6220

@article{e0b89c076a714bbe87c4f699903aa2ab,

title = "Genetic predisposition to metabolically unfavourable adiposity and prostate cancer risk: A Mendelian randomization analysis",

abstract = "Background: The associations of adiposity with aggressive prostate cancer risk are unclear. Using two-sample Mendelian randomization, we assessed the association of metabolically unfavourable adiposity (UFA), favourable adiposity (FA) and for comparison body mass index (BMI), with prostate cancer, including aggressive prostate cancer.Methods: We examined the association of these genetically predicted adiposity-related traits with risk of prostate cancer overall, aggressive and early onset disease using outcome summary statistics from the PRACTICAL consortium (including 15,167 aggressive cases).Results: In inverse-variance weighted models, there was little evidence that genetically predicted one standard deviation higher UFA, FA and BMI were associated with aggressive prostate cancer [OR: 0.85 (95% CI:0.61-1.19), 0.80 (0.53-1.23) and 0.97 (0.88-1.08), respectively]; these associations were largely consistent in sensitivity analyses accounting for horizontal pleiotropy. There was no strong evidence that genetically determined UFA, FA or BMI were associated with overall prostate cancer or early age of onset prostate cancer.Conclusions: We did not find differences in the associations of UFA and FA with prostate cancer risk, which suggest that adiposity is unlikely to influence prostate cancer via the metabolic factors assessed; however, these did not cover some aspects related to metabolic health that may link obesity with aggressive prostate cancer, which should be explored in future studies.",

author = "Aurora Perez-Cornago and Karl Smith-Byrne and Emma Hazelwood and Watling, {Cody Z.} and Susan Martin and Timothy Frayling and Lewis, {Sarah J} and Martin, {Richard M} and Hanieh Yaghootkar and Travis, {Ruth C.} and Key, {Timothy J.}",

note = "Funding Information: This research was funded by Cancer Research UK Population Research Fellowship number C60192/A28516 to APC. APC is also supported by the World Cancer Research Fund (WCRF UK), as part of the Word Cancer Research Fund International grant programme (2019/1953). KS‐M, RT and TJK are supported by Cancer Research UK (C8221/A29017). EH is supported by a Cancer Research UK Population Research Committee Studentship (C18281/A30905). RMM is a National Institute for Health Research Senior Investigator (NIHR202411). EH, RMM and SJL are supported by a Cancer Research UK 25 (C18281/A29019) programme grant (the Integrative Cancer Epidemiology Programme). RMM is also supported by the NIHR Bristol Biomedical Research Centre which is funded by the NIHR (BRC‐1215‐20011) and is a partnership between University Hospitals Bristol and Weston NHS Foundation Trust and the University of Bristol. RMM and EH are affiliated with the Medical Research Council Integrative Epidemiology Unit at the University of Bristol which is supported by the Medical Research Council (MC_UU_00011/1, MC_UU_00011/3, MC_UU_00011/6 and MC_UU_00011/4) and the University of Bristol. Department of Health and Social Care disclaimer: The views expressed are those of the author(s) and not necessarily those of the NHS, the NIHR or the Department of Health and Social Care. SM is supported by an {\textquoteleft}Expanding excellence in England{\textquoteright} award from Research England and by the National Institute for Health and Care Research Exeter Biomedical Research Centre. Publisher Copyright: {\textcopyright} 2023 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.",

year = "2023",

month = jun,

day = "12",

doi = "10.1002/cam4.6220",

language = "English",

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T1 - Genetic predisposition to metabolically unfavourable adiposity and prostate cancer risk

T2 - A Mendelian randomization analysis

AU - Perez-Cornago, Aurora

AU - Smith-Byrne, Karl

AU - Hazelwood, Emma

AU - Watling, Cody Z.

AU - Martin, Susan

AU - Frayling, Timothy

AU - Lewis, Sarah J

AU - Martin, Richard M

AU - Yaghootkar, Hanieh

AU - Travis , Ruth C.

AU - Key , Timothy J.

N1 - Funding Information: This research was funded by Cancer Research UK Population Research Fellowship number C60192/A28516 to APC. APC is also supported by the World Cancer Research Fund (WCRF UK), as part of the Word Cancer Research Fund International grant programme (2019/1953). KS‐M, RT and TJK are supported by Cancer Research UK (C8221/A29017). EH is supported by a Cancer Research UK Population Research Committee Studentship (C18281/A30905). RMM is a National Institute for Health Research Senior Investigator (NIHR202411). EH, RMM and SJL are supported by a Cancer Research UK 25 (C18281/A29019) programme grant (the Integrative Cancer Epidemiology Programme). RMM is also supported by the NIHR Bristol Biomedical Research Centre which is funded by the NIHR (BRC‐1215‐20011) and is a partnership between University Hospitals Bristol and Weston NHS Foundation Trust and the University of Bristol. RMM and EH are affiliated with the Medical Research Council Integrative Epidemiology Unit at the University of Bristol which is supported by the Medical Research Council (MC_UU_00011/1, MC_UU_00011/3, MC_UU_00011/6 and MC_UU_00011/4) and the University of Bristol. Department of Health and Social Care disclaimer: The views expressed are those of the author(s) and not necessarily those of the NHS, the NIHR or the Department of Health and Social Care. SM is supported by an ‘Expanding excellence in England’ award from Research England and by the National Institute for Health and Care Research Exeter Biomedical Research Centre. Publisher Copyright: © 2023 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.

PY - 2023/6/12

Y1 - 2023/6/12

N2 - Background: The associations of adiposity with aggressive prostate cancer risk are unclear. Using two-sample Mendelian randomization, we assessed the association of metabolically unfavourable adiposity (UFA), favourable adiposity (FA) and for comparison body mass index (BMI), with prostate cancer, including aggressive prostate cancer.Methods: We examined the association of these genetically predicted adiposity-related traits with risk of prostate cancer overall, aggressive and early onset disease using outcome summary statistics from the PRACTICAL consortium (including 15,167 aggressive cases).Results: In inverse-variance weighted models, there was little evidence that genetically predicted one standard deviation higher UFA, FA and BMI were associated with aggressive prostate cancer [OR: 0.85 (95% CI:0.61-1.19), 0.80 (0.53-1.23) and 0.97 (0.88-1.08), respectively]; these associations were largely consistent in sensitivity analyses accounting for horizontal pleiotropy. There was no strong evidence that genetically determined UFA, FA or BMI were associated with overall prostate cancer or early age of onset prostate cancer.Conclusions: We did not find differences in the associations of UFA and FA with prostate cancer risk, which suggest that adiposity is unlikely to influence prostate cancer via the metabolic factors assessed; however, these did not cover some aspects related to metabolic health that may link obesity with aggressive prostate cancer, which should be explored in future studies.

AB - Background: The associations of adiposity with aggressive prostate cancer risk are unclear. Using two-sample Mendelian randomization, we assessed the association of metabolically unfavourable adiposity (UFA), favourable adiposity (FA) and for comparison body mass index (BMI), with prostate cancer, including aggressive prostate cancer.Methods: We examined the association of these genetically predicted adiposity-related traits with risk of prostate cancer overall, aggressive and early onset disease using outcome summary statistics from the PRACTICAL consortium (including 15,167 aggressive cases).Results: In inverse-variance weighted models, there was little evidence that genetically predicted one standard deviation higher UFA, FA and BMI were associated with aggressive prostate cancer [OR: 0.85 (95% CI:0.61-1.19), 0.80 (0.53-1.23) and 0.97 (0.88-1.08), respectively]; these associations were largely consistent in sensitivity analyses accounting for horizontal pleiotropy. There was no strong evidence that genetically determined UFA, FA or BMI were associated with overall prostate cancer or early age of onset prostate cancer.Conclusions: We did not find differences in the associations of UFA and FA with prostate cancer risk, which suggest that adiposity is unlikely to influence prostate cancer via the metabolic factors assessed; however, these did not cover some aspects related to metabolic health that may link obesity with aggressive prostate cancer, which should be explored in future studies.

U2 - 10.1002/cam4.6220

DO - 10.1002/cam4.6220

M3 - Article (Academic Journal)

C2 - 37305903

SN - 2045-7634

VL - 12

SP - 16482

EP - 16489

JO - Cancer Medicine

JF - Cancer Medicine

IS - 15

ER -

Genetic predisposition to metabolically unfavourable adiposity and prostate cancer risk: A Mendelian randomization analysis

Abstract

Bibliographical note

Structured keywords

UN SDGs

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Projects

8074 (C18281/A29019) ICEP2 - Programme Award: Towards improved casual evidence and enhanced prediction of cancer risk and survival

Cite this