Neither Hormonal Factors Nor AGEs Explain Lower Prostate Cancer Risk in Older Men With Diabetes Mellitus

Yi X. Chan, Helman Alfonso, P. Gerry Fegan, Leon Flicker, Bu B. Yeap

Research output: Contribution to journalArticle

Abstract

CONTEXT: Diabetes mellitus is conventionally associated with an increased risk of cancer; however, inverse associations of diabetes with prostate cancer are well described. Mechanisms are unclear, although hormonal factors, including alterations in sex hormone and IGF1 concentrations due to metabolic disturbances, have been hypothesized to play a role. OBJECTIVE: To assess sex hormones, IGF1, glucose, and advanced glycation end products (AGEs) as potential mediators of the association between diabetes mellitus and prostate cancer. DESIGN AND PARTICIPANTS: Longitudinal cohort study. The association of baseline diabetes with prostate cancer incidence was assessed using proportional hazards competing risks analysis in 3149 men followed for 12 years. Baseline hormone, glucose, and carboxymethyllysine (CML) levels were examined as potential mediators of this association. RESULTS: Diabetes was associated with a lower prostate cancer risk (fully adjusted subhazard ratio, 0.63; 95% CI, 0.43 to 0.92; P = 0.017). This association was unchanged after accounting for testosterone, DHT, estradiol, or SHBG. Similarly, the addition of IGF1 or its binding proteins 1 and 3, or glucose, did not alter this association. CML was not associated with the risk of prostate cancer, and additional correction for CML in the fully adjusted model did not alter the inverse association of diabetes and prostate cancer risk. CONCLUSIONS: In this study, alterations in sex hormone, IGF1, glucose, and CML levels did not account for the inverse association of diabetes and prostate cancer risk. Further studies are required to provide more insight into underlying causes of this association.

Original languageEnglish
Pages (from-to)6017-6024
Number of pages8
JournalThe Journal of clinical endocrinology and metabolism
Volume104
Issue number12
DOIs
Publication statusPublished - 1 Dec 2019

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Medical problems
Prostatic Neoplasms
Diabetes Mellitus
Gonadal Steroid Hormones
Glucose
Advanced Glycosylation End Products
Risk analysis
Longitudinal Studies
Testosterone
Estradiol
Hazards
Carrier Proteins
Cohort Studies
Hormones
N(6)-carboxymethyllysine
Incidence
Neoplasms

Cite this

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title = "Neither Hormonal Factors Nor AGEs Explain Lower Prostate Cancer Risk in Older Men With Diabetes Mellitus",
abstract = "CONTEXT: Diabetes mellitus is conventionally associated with an increased risk of cancer; however, inverse associations of diabetes with prostate cancer are well described. Mechanisms are unclear, although hormonal factors, including alterations in sex hormone and IGF1 concentrations due to metabolic disturbances, have been hypothesized to play a role. OBJECTIVE: To assess sex hormones, IGF1, glucose, and advanced glycation end products (AGEs) as potential mediators of the association between diabetes mellitus and prostate cancer. DESIGN AND PARTICIPANTS: Longitudinal cohort study. The association of baseline diabetes with prostate cancer incidence was assessed using proportional hazards competing risks analysis in 3149 men followed for 12 years. Baseline hormone, glucose, and carboxymethyllysine (CML) levels were examined as potential mediators of this association. RESULTS: Diabetes was associated with a lower prostate cancer risk (fully adjusted subhazard ratio, 0.63; 95{\%} CI, 0.43 to 0.92; P = 0.017). This association was unchanged after accounting for testosterone, DHT, estradiol, or SHBG. Similarly, the addition of IGF1 or its binding proteins 1 and 3, or glucose, did not alter this association. CML was not associated with the risk of prostate cancer, and additional correction for CML in the fully adjusted model did not alter the inverse association of diabetes and prostate cancer risk. CONCLUSIONS: In this study, alterations in sex hormone, IGF1, glucose, and CML levels did not account for the inverse association of diabetes and prostate cancer risk. Further studies are required to provide more insight into underlying causes of this association.",
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Neither Hormonal Factors Nor AGEs Explain Lower Prostate Cancer Risk in Older Men With Diabetes Mellitus. / Chan, Yi X.; Alfonso, Helman; Fegan, P. Gerry; Flicker, Leon; Yeap, Bu B.

In: The Journal of clinical endocrinology and metabolism, Vol. 104, No. 12, 01.12.2019, p. 6017-6024.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Neither Hormonal Factors Nor AGEs Explain Lower Prostate Cancer Risk in Older Men With Diabetes Mellitus

AU - Chan, Yi X.

AU - Alfonso, Helman

AU - Fegan, P. Gerry

AU - Flicker, Leon

AU - Yeap, Bu B.

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N2 - CONTEXT: Diabetes mellitus is conventionally associated with an increased risk of cancer; however, inverse associations of diabetes with prostate cancer are well described. Mechanisms are unclear, although hormonal factors, including alterations in sex hormone and IGF1 concentrations due to metabolic disturbances, have been hypothesized to play a role. OBJECTIVE: To assess sex hormones, IGF1, glucose, and advanced glycation end products (AGEs) as potential mediators of the association between diabetes mellitus and prostate cancer. DESIGN AND PARTICIPANTS: Longitudinal cohort study. The association of baseline diabetes with prostate cancer incidence was assessed using proportional hazards competing risks analysis in 3149 men followed for 12 years. Baseline hormone, glucose, and carboxymethyllysine (CML) levels were examined as potential mediators of this association. RESULTS: Diabetes was associated with a lower prostate cancer risk (fully adjusted subhazard ratio, 0.63; 95% CI, 0.43 to 0.92; P = 0.017). This association was unchanged after accounting for testosterone, DHT, estradiol, or SHBG. Similarly, the addition of IGF1 or its binding proteins 1 and 3, or glucose, did not alter this association. CML was not associated with the risk of prostate cancer, and additional correction for CML in the fully adjusted model did not alter the inverse association of diabetes and prostate cancer risk. CONCLUSIONS: In this study, alterations in sex hormone, IGF1, glucose, and CML levels did not account for the inverse association of diabetes and prostate cancer risk. Further studies are required to provide more insight into underlying causes of this association.

AB - CONTEXT: Diabetes mellitus is conventionally associated with an increased risk of cancer; however, inverse associations of diabetes with prostate cancer are well described. Mechanisms are unclear, although hormonal factors, including alterations in sex hormone and IGF1 concentrations due to metabolic disturbances, have been hypothesized to play a role. OBJECTIVE: To assess sex hormones, IGF1, glucose, and advanced glycation end products (AGEs) as potential mediators of the association between diabetes mellitus and prostate cancer. DESIGN AND PARTICIPANTS: Longitudinal cohort study. The association of baseline diabetes with prostate cancer incidence was assessed using proportional hazards competing risks analysis in 3149 men followed for 12 years. Baseline hormone, glucose, and carboxymethyllysine (CML) levels were examined as potential mediators of this association. RESULTS: Diabetes was associated with a lower prostate cancer risk (fully adjusted subhazard ratio, 0.63; 95% CI, 0.43 to 0.92; P = 0.017). This association was unchanged after accounting for testosterone, DHT, estradiol, or SHBG. Similarly, the addition of IGF1 or its binding proteins 1 and 3, or glucose, did not alter this association. CML was not associated with the risk of prostate cancer, and additional correction for CML in the fully adjusted model did not alter the inverse association of diabetes and prostate cancer risk. CONCLUSIONS: In this study, alterations in sex hormone, IGF1, glucose, and CML levels did not account for the inverse association of diabetes and prostate cancer risk. Further studies are required to provide more insight into underlying causes of this association.

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