Perturbations in the blood metabolome up to a decade before prostate cancer diagnosis in 4387 matched case-control sets from the European Prospective Investigation into Cancer and Nutrition

Zoe S Grenville; Urwah Noor; Sabina Rinaldi; Marc J Gunter; Pietro Ferrari; Claudia Agnoli; Pilar Amiano; Alberto Catalano; María Dolores Chirlaque; Sofia Christakoudi; Marcela Guevara; Matthias Johansson; Rudolf Kaaks; Verena Katzke; Giovanna Masala; Anja Olsen; Keren Papier; Maria-Jose Sánchez; Matthias B Schulze; Anne Tjønneland; Tammy Y N Tong; Rosario Tumino; Elisabete Weiderpass; Raul Zamora-Ros; Timothy J Key; Karl Smith-Byrne; Julie A Schmidt; Ruth C Travis

doi:10.1002/ijc.35208

Perturbations in the blood metabolome up to a decade before prostate cancer diagnosis in 4387 matched case-control sets from the European Prospective Investigation into Cancer and Nutrition

Zoe S Grenville^*, Urwah Noor, Sabina Rinaldi, Marc J Gunter, Pietro Ferrari, Claudia Agnoli, Pilar Amiano, Alberto Catalano, María Dolores Chirlaque, Sofia Christakoudi, Marcela Guevara, Matthias Johansson, Rudolf Kaaks, Verena Katzke, Giovanna Masala, Anja Olsen, Keren Papier, Maria-Jose Sánchez, Matthias B Schulze, Anne TjønnelandTammy Y N Tong, Rosario Tumino, Elisabete Weiderpass, Raul Zamora-Ros, Timothy J Key, Karl Smith-Byrne, Julie A Schmidt, Ruth C Travis

^*Corresponding author for this work

Research output: Contribution to journal/Conference contribution in journal/Contribution to newspaper › Journal article › Research › peer-review

Abstract

Measuring pre-diagnostic blood metabolites may help identify novel risk factors for prostate cancer. Using data from 4387 matched case–control pairs from the European Prospective Investigation into Cancer and Nutrition (EPIC) study, we investigated the associations of 148 individual metabolites and three previously defined metabolite patterns with prostate cancer risk. Metabolites were measured by liquid chromatography-mass spectrometry. Multivariable-adjusted conditional logistic regression was used to estimate the odds ratio per standard deviation increase in log metabolite concentration and metabolite patterns (OR1SD) for prostate cancer overall, and for advanced, high-grade, aggressive. We corrected for multiple testing using the Benjamini–Hochberg method. Overall, there were no associations between specific metabolites or metabolite patterns and overall, aggressive, or high-grade prostate cancer that passed the multiple testing threshold (padj <0.05). Six phosphatidylcholines (PCs) were inversely associated with advanced prostate cancer diagnosed at or within 10 years of blood collection. metabolite patterns 1 (64 PCs and three hydroxysphingomyelins) and 2 (two acylcarnitines, glutamate, ornithine, and taurine) were also inversely associated with advanced prostate cancer; when stratified by follow-up time, these associations were observed for diagnoses at or within 10 years of recruitment (OR_1SD 0.80, 95% CI 0.66–0.96 and 0.76, 0.59–0.97, respectively) but were weaker after longer follow-up (0.95, 0.82–1.10 and 0.85, 0.67–1.06). Pattern 3 (8 lyso PCs) was associated with prostate cancer death (0.82, 0.68–0.98). Our results suggest that the plasma metabolite profile changes in response to the presence of prostate cancer up to a decade before detection of advanced-stage disease.

Original language	English
Journal	International Journal of Cancer
Volume	156
Issue	5
Pages (from-to)	943-952
Number of pages	10
ISSN	0020-7136
DOIs	https://doi.org/10.1002/ijc.35208
Publication status	Published - 1 Mar 2025

Keywords

Cancer biomarkers
European Prospective Investigation into Cancer and Nutrition (EPIC)
metabolomics
prospective cohort
prostate cancer

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Grenville, Z. S., Noor, U., Rinaldi, S., Gunter, M. J., Ferrari, P., Agnoli, C., Amiano, P., Catalano, A., Chirlaque, M. D., Christakoudi, S., Guevara, M., Johansson, M., Kaaks, R., Katzke, V., Masala, G., Olsen, A., Papier, K., Sánchez, M.-J., Schulze, M. B., ... Travis, R. C. (2025). Perturbations in the blood metabolome up to a decade before prostate cancer diagnosis in 4387 matched case-control sets from the European Prospective Investigation into Cancer and Nutrition. International Journal of Cancer, 156(5), 943-952. https://doi.org/10.1002/ijc.35208

@article{a1558e6c71ab4103ae30eb145e5a65ec,

title = "Perturbations in the blood metabolome up to a decade before prostate cancer diagnosis in 4387 matched case-control sets from the European Prospective Investigation into Cancer and Nutrition",

abstract = "Measuring pre-diagnostic blood metabolites may help identify novel risk factors for prostate cancer. Using data from 4387 matched case–control pairs from the European Prospective Investigation into Cancer and Nutrition (EPIC) study, we investigated the associations of 148 individual metabolites and three previously defined metabolite patterns with prostate cancer risk. Metabolites were measured by liquid chromatography-mass spectrometry. Multivariable-adjusted conditional logistic regression was used to estimate the odds ratio per standard deviation increase in log metabolite concentration and metabolite patterns (OR1SD) for prostate cancer overall, and for advanced, high-grade, aggressive. We corrected for multiple testing using the Benjamini–Hochberg method. Overall, there were no associations between specific metabolites or metabolite patterns and overall, aggressive, or high-grade prostate cancer that passed the multiple testing threshold (padj <0.05). Six phosphatidylcholines (PCs) were inversely associated with advanced prostate cancer diagnosed at or within 10 years of blood collection. metabolite patterns 1 (64 PCs and three hydroxysphingomyelins) and 2 (two acylcarnitines, glutamate, ornithine, and taurine) were also inversely associated with advanced prostate cancer; when stratified by follow-up time, these associations were observed for diagnoses at or within 10 years of recruitment (OR1SD 0.80, 95% CI 0.66–0.96 and 0.76, 0.59–0.97, respectively) but were weaker after longer follow-up (0.95, 0.82–1.10 and 0.85, 0.67–1.06). Pattern 3 (8 lyso PCs) was associated with prostate cancer death (0.82, 0.68–0.98). Our results suggest that the plasma metabolite profile changes in response to the presence of prostate cancer up to a decade before detection of advanced-stage disease.",

keywords = "Cancer biomarkers, European Prospective Investigation into Cancer and Nutrition (EPIC), metabolomics, prospective cohort, prostate cancer",

author = "Grenville, {Zoe S} and Urwah Noor and Sabina Rinaldi and Gunter, {Marc J} and Pietro Ferrari and Claudia Agnoli and Pilar Amiano and Alberto Catalano and Chirlaque, {Mar{\'i}a Dolores} and Sofia Christakoudi and Marcela Guevara and Matthias Johansson and Rudolf Kaaks and Verena Katzke and Giovanna Masala and Anja Olsen and Keren Papier and Maria-Jose S{\'a}nchez and Schulze, {Matthias B} and Anne Tj{\o}nneland and Tong, {Tammy Y N} and Rosario Tumino and Elisabete Weiderpass and Raul Zamora-Ros and Key, {Timothy J} and Karl Smith-Byrne and Schmidt, {Julie A} and Travis, {Ruth C}",

year = "2025",

month = mar,

day = "1",

doi = "10.1002/ijc.35208",

language = "English",

volume = "156",

pages = "943--952",

journal = "International Journal of Cancer",

issn = "0020-7136",

publisher = "John Wiley & Sons Inc.",

number = "5",

}

Grenville, ZS, Noor, U, Rinaldi, S, Gunter, MJ, Ferrari, P, Agnoli, C, Amiano, P, Catalano, A, Chirlaque, MD, Christakoudi, S, Guevara, M, Johansson, M, Kaaks, R, Katzke, V, Masala, G, Olsen, A, Papier, K, Sánchez, M-J, Schulze, MB, Tjønneland, A, Tong, TYN, Tumino, R, Weiderpass, E, Zamora-Ros, R, Key, TJ, Smith-Byrne, K, Schmidt, JA & Travis, RC 2025, 'Perturbations in the blood metabolome up to a decade before prostate cancer diagnosis in 4387 matched case-control sets from the European Prospective Investigation into Cancer and Nutrition', International Journal of Cancer, vol. 156, no. 5, pp. 943-952. https://doi.org/10.1002/ijc.35208

Perturbations in the blood metabolome up to a decade before prostate cancer diagnosis in 4387 matched case-control sets from the European Prospective Investigation into Cancer and Nutrition. / Grenville, Zoe S; Noor, Urwah; Rinaldi, Sabina et al.
In: International Journal of Cancer, Vol. 156, No. 5, 01.03.2025, p. 943-952.

Research output: Contribution to journal/Conference contribution in journal/Contribution to newspaper › Journal article › Research › peer-review

TY - JOUR

T1 - Perturbations in the blood metabolome up to a decade before prostate cancer diagnosis in 4387 matched case-control sets from the European Prospective Investigation into Cancer and Nutrition

AU - Grenville, Zoe S

AU - Noor, Urwah

AU - Rinaldi, Sabina

AU - Gunter, Marc J

AU - Ferrari, Pietro

AU - Agnoli, Claudia

AU - Amiano, Pilar

AU - Catalano, Alberto

AU - Chirlaque, María Dolores

AU - Christakoudi, Sofia

AU - Guevara, Marcela

AU - Johansson, Matthias

AU - Kaaks, Rudolf

AU - Katzke, Verena

AU - Masala, Giovanna

AU - Olsen, Anja

AU - Papier, Keren

AU - Sánchez, Maria-Jose

AU - Schulze, Matthias B

AU - Tjønneland, Anne

AU - Tong, Tammy Y N

AU - Tumino, Rosario

AU - Weiderpass, Elisabete

AU - Zamora-Ros, Raul

AU - Key, Timothy J

AU - Smith-Byrne, Karl

AU - Schmidt, Julie A

AU - Travis, Ruth C

PY - 2025/3/1

Y1 - 2025/3/1

N2 - Measuring pre-diagnostic blood metabolites may help identify novel risk factors for prostate cancer. Using data from 4387 matched case–control pairs from the European Prospective Investigation into Cancer and Nutrition (EPIC) study, we investigated the associations of 148 individual metabolites and three previously defined metabolite patterns with prostate cancer risk. Metabolites were measured by liquid chromatography-mass spectrometry. Multivariable-adjusted conditional logistic regression was used to estimate the odds ratio per standard deviation increase in log metabolite concentration and metabolite patterns (OR1SD) for prostate cancer overall, and for advanced, high-grade, aggressive. We corrected for multiple testing using the Benjamini–Hochberg method. Overall, there were no associations between specific metabolites or metabolite patterns and overall, aggressive, or high-grade prostate cancer that passed the multiple testing threshold (padj <0.05). Six phosphatidylcholines (PCs) were inversely associated with advanced prostate cancer diagnosed at or within 10 years of blood collection. metabolite patterns 1 (64 PCs and three hydroxysphingomyelins) and 2 (two acylcarnitines, glutamate, ornithine, and taurine) were also inversely associated with advanced prostate cancer; when stratified by follow-up time, these associations were observed for diagnoses at or within 10 years of recruitment (OR1SD 0.80, 95% CI 0.66–0.96 and 0.76, 0.59–0.97, respectively) but were weaker after longer follow-up (0.95, 0.82–1.10 and 0.85, 0.67–1.06). Pattern 3 (8 lyso PCs) was associated with prostate cancer death (0.82, 0.68–0.98). Our results suggest that the plasma metabolite profile changes in response to the presence of prostate cancer up to a decade before detection of advanced-stage disease.

AB - Measuring pre-diagnostic blood metabolites may help identify novel risk factors for prostate cancer. Using data from 4387 matched case–control pairs from the European Prospective Investigation into Cancer and Nutrition (EPIC) study, we investigated the associations of 148 individual metabolites and three previously defined metabolite patterns with prostate cancer risk. Metabolites were measured by liquid chromatography-mass spectrometry. Multivariable-adjusted conditional logistic regression was used to estimate the odds ratio per standard deviation increase in log metabolite concentration and metabolite patterns (OR1SD) for prostate cancer overall, and for advanced, high-grade, aggressive. We corrected for multiple testing using the Benjamini–Hochberg method. Overall, there were no associations between specific metabolites or metabolite patterns and overall, aggressive, or high-grade prostate cancer that passed the multiple testing threshold (padj <0.05). Six phosphatidylcholines (PCs) were inversely associated with advanced prostate cancer diagnosed at or within 10 years of blood collection. metabolite patterns 1 (64 PCs and three hydroxysphingomyelins) and 2 (two acylcarnitines, glutamate, ornithine, and taurine) were also inversely associated with advanced prostate cancer; when stratified by follow-up time, these associations were observed for diagnoses at or within 10 years of recruitment (OR1SD 0.80, 95% CI 0.66–0.96 and 0.76, 0.59–0.97, respectively) but were weaker after longer follow-up (0.95, 0.82–1.10 and 0.85, 0.67–1.06). Pattern 3 (8 lyso PCs) was associated with prostate cancer death (0.82, 0.68–0.98). Our results suggest that the plasma metabolite profile changes in response to the presence of prostate cancer up to a decade before detection of advanced-stage disease.

KW - Cancer biomarkers

KW - European Prospective Investigation into Cancer and Nutrition (EPIC)

KW - metabolomics

KW - prospective cohort

KW - prostate cancer

UR - http://www.scopus.com/inward/record.url?scp=85205905877&partnerID=8YFLogxK

U2 - 10.1002/ijc.35208

DO - 10.1002/ijc.35208

M3 - Journal article

C2 - 39378119

SN - 0020-7136

VL - 156

SP - 943

EP - 952

JO - International Journal of Cancer

JF - International Journal of Cancer

IS - 5

ER -

Perturbations in the blood metabolome up to a decade before prostate cancer diagnosis in 4387 matched case-control sets from the European Prospective Investigation into Cancer and Nutrition

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Keywords

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