Sitagliptin may reduce prostate cancer risk in male patients with type 2 diabetes

Abstract Background: The aim of this study was to determine whether type 2 diabetes mellitus and treatment with metformin is associated with prostate cancer risk. Methods: Male patients with diagnosis of type 2 diabetes during the period of 2000 – 2016 were identified in the National Health Insurance Fund database. The prostate cancer cases were identified by pooling these records from the national Cancer Registry. The calculation of prostate cancer stardardized incidence ratios (SIRs) was composed as a ratio of observed number of cancer case in people with diagnosis of diabetes to the expected number of cancer cases in the underlying general population. Results: Overall, 64,000 males diagnosed with diabetes in Lithuania between 2000 and 2016 were included in the final cohort. 2,754 prostate cancers were observed versus 3,111.26 expected within the period of observation entailing an SIR of 0.89 (95% CI: 0.85–0.92). Significantly lower risk of prostate cancer was found in diabetes patients in all age groups, there were no differences in prostate cancer risk by time since diagnosis of diabetes. Significantly lower risk of prostate cancer also was found in both metformin users and never-users’ groups, with higher risk reduction in metformin users (SIR 0.71, 95% CI: 0.68–0.75) than in diabetes patients never-users (SIR 0.88, 95% CI: 0.80–0.96). Conclusions: In this large population-based study we found a significantly decreased risk of prostate cancer among men with diabetes and metformin users. However, the risk of prostate cancer showed no clear trend with diabetes duration and cumulative metformin dose.

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Impact of glycemic traits, type 2 diabetes and metformin use on breast and prostate cancer risk: a Mendelian randomization study

BMJ Open Diabetes Research & Care ◽

10.1136/bmjdrc-2019-000872 ◽

2019 ◽

Vol 7 (1) ◽

pp. e000872 ◽

Cited By ~ 6

Author(s):

Shiu Lun Au Yeung ◽

Catherine Mary Schooling

Keyword(s):

Breast Cancer ◽

Prostate Cancer ◽

Type 2 Diabetes ◽

Cancer Risk ◽

Fasting Glucose ◽

Prostate Cancer Risk ◽

Immortal Time Bias ◽

Log Odds ◽

Breast And Prostate Cancer

ObjectivesObservational studies suggest glycemic traits and type 2 diabetes are positively associated, and metformin inversely associated with breast and prostate cancer risk. However, observational studies are susceptible to unmeasured confounding while studies of metformin use are also vulnerable to immortal time bias. The use of Mendelian randomization may reduce confounding due to random allocation of relevant genetic markers at birth, and may reduce immortal time bias (for metformin-related variants analysis) since the start of exposure is at birth.Research design and methodsWe identified strong genetic predictors of fasting glucose, glycated hemoglobin, and type 2 diabetes from the Meta-Analyses of Glucose and Insulin-related traits Consortium and Diabetes Genetics Replication And Meta-analysis Consortium (n=140 595 for glucose; n=123 665 for HbA1c; n=898 130 for type 2 diabetes) and of AMPK-instrumented HbA1c reduction as a proxy of metformin and applied them to large genome-wide association studies of breast cancer (Breast Cancer Association Consortium; BCAC) and prostate cancer (Prostate Cancer Association Group to Investigate Cancer-Associated Alterations in the Genome; PRACTICAL). We used inverse variance weighting to obtain estimates. Sensitivity analyses included use of MR-Egger, weighted median, exclusion of pleiotropic instruments, and validation using UK Biobank (breast cancer only).ResultsThere was no association of fasting glucose (OR 1.03 per mmol/L, 95% CI 0.85 to 1.25), HbA1c (OR 1.02 per %, 95% CI 0.73 to 1.45), or type 2 diabetes (OR 0.98 per log odds, 95% CI 0.95 to 1.01) with breast cancer in BCAC, with similar findings from UK Biobank. There was no association of fasting glucose (OR 0.93 per mmol/L, 95% CI 0.73 to 1.17), HbA1c (OR 0.90 per %, 95% CI 0.58 to 1.40) or type 2 diabetes (OR 1.02 per log odds, 95% CI 0.97 to 1.07) with prostate cancer in PRACTICAL. No strong evidence was observed for AMPK-instrumented HbA1c reduction on cancer risk.ConclusionGlycemic traits and type 2 diabetes unlikely cause breast and prostate cancer. Whether metformin can be repurposed for cancer prevention remains unclear.

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Circulating selenium and prostate cancer risk: a Mendelian randomization analysis

10.1101/223248 ◽

2017 ◽

Cited By ~ 1

Author(s):

James Yarmolinsky ◽

Carolina Bonilla ◽

Philip C Haycock ◽

Ryan JQ Langdon ◽

Luca A Lotta ◽

...

Keyword(s):

Prostate Cancer ◽

Type 2 Diabetes ◽

Cancer Risk ◽

Mendelian Randomization ◽

Prostate Cancer Risk ◽

Selenium Supplementation ◽

High Grade ◽

Mendelian Randomization Analysis ◽

Randomization Analysis

AbstractIn the Selenium and Vitamin E Cancer Prevention Trial (SELECT), selenium supplementation (causing a median 114 μg/L increase in circulating selenium) did not lower overall prostate cancer risk, but increased risk of high-grade prostate cancer and type 2 diabetes. Mendelian randomization analysis uses genetic variants to proxy modifiable risk factors and can strengthen causal inference in observational studies. We constructed a genetic risk score comprising eleven single-nucleotide polymorphisms robustly (P<5x10−8) associated with circulating selenium in genome-wide association studies. In a Mendelian randomization analysis of 72,729 men in the PRACTICAL Consortium (44,825 cases, 27,904 controls), 114 μg/L higher genetically-elevated circulating selenium was not associated with prostate cancer (OR: 1.01; 95% CI: 0.89-1.13). Concordant with findings from SELECT, selenium was weakly associated with advanced (including high-grade) prostate cancer (OR: 1.21; 95% CI: 0.98-1.49) and type 2 diabetes (OR: 1.18; 95% CI: 0.97-1.43; in a type 2 diabetes GWAS meta-analysis with up to 49,266 cases, 249,906 controls). Mendelian randomization mirrored the outcome of selenium supplementation in SELECT and may offer an approach for the prioritization of interventions for follow-up in large-scale randomized controlled trials.

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