Abstract

Simple SummaryMen’s pubertal timing lacks distinct markers that are easily available retrospectively. Therefore, the association between objectively assessed pubertal timing and the risk of prostate cancer is unknown. Our aim was to evaluate the association between the age at the pubertal growth spurt, an objective assessment of pubertal timing, and the risk of prostate cancer and high-risk prostate cancer. We used a population-based cohort including over 30,000 men with age at the pubertal growth spurt available and with follow-up in high quality national registers. During 1.4 million years of follow up, 1759 cases of prostate cancer were diagnosed. We demonstrate that late pubertal timing is a protective factor for prostate cancer, and especially for the clinically important high-risk or metastatic prostate cancer. Identification of early life risk- and protective factors for prostate cancer could provide new opportunities to unravel the underlying biological mechanism of the origins of prostate cancer.Previous studies of pubertal timing and the risk of prostate cancer have used self-reported markers of pubertal development, recalled in mid-life, and the results have been inconclusive. Our aim was to evaluate the age at the pubertal growth spurt, an objective marker of pubertal timing, and the risk of prostate cancer and high-risk prostate cancer. This population-based cohort study included 31,971 men with sufficient height measurements to calculate age at peak height velocity (PHV). Outcomes were accessed through national registers. Hazard ratios (HR) and 95% confidence intervals (CI) were estimated by Cox regressions with follow up starting at 20 years of age. In total, 1759 cases of prostate cancer including 449 high-risk were diagnosed during follow up. Mean follow up was 42 years (standard deviation 10.0). Compared to quintiles 2–4 (Q2–4), men in the highest age at PHV quintile (Q5) had lower risk of prostate cancer (HR 0.83, 95% CI 0.73–0.94), and of high-risk prostate cancer (0.73; 0.56–0.94). In an exploratory analysis with follow up starting at age at PHV, late pubertal timing was no longer associated with reduced risk of prostate cancer. Later pubertal timing was associated with reduced risk of prostate cancer and especially high-risk prostate cancer. We propose that the risk of prostate cancer might be influenced by the number of years with exposure to adult levels of sex steroids.

Highlights

  • Prostate cancer is the most frequent malignancy in men in both Europe and the USA, with 248,000 new cases and 34,000 deaths estimated in the USA in 2021 [1,2]

  • We demonstrate lower risk of overall prostate cancer and especially of highrisk or metastatic prostate cancer among individuals with late pubertal timing, compared with individuals with average pubertal timing

  • Among men with prostate cancer, late pubertal timing was associated with prostate cancer with better prognosis

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Summary

Introduction

Prostate cancer is the most frequent malignancy in men in both Europe and the USA, with 248,000 new cases and 34,000 deaths estimated in the USA in 2021 [1,2]. The prevalence of prostate cancer varies largely in different regions of the world. It is most common among black men in the USA and the Caribbean, followed by white men in the USA and the Scandinavian countries, while it is uncommon in the southeast of Asia [3]. Both genetical and environmental factors contributes to the significant geographical variations.

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