Abstract Background: The parenchyma of the pineal gland, an endocrine gland in the brain, produces the circadian hormone melatonin. Previously, we found low levels of melatonin were associated with an increased risk for advanced prostate cancer. This study used data from men in the Age, Gene/Environment Susceptibility-Reykjavik (AGES-Reykjavik) Study to evaluate the relationship between pineal volume, melatonin levels, and prostate cancer risk. Methods: Participants were enrolled in the AGES-Reykjavik Study from 2002 to 2006 and underwent detailed clinical assessments at baseline that included biospecimen collection, MRI of the brain, medical history, and health questionnaires on dietary and lifestyle factors. We included 802 men who had information on pineal size, where parenchyma, calcification, and cyst volume were estimated individually and manually from the MRIs. Cox proportional hazards regression was used to calculate hazard ratios and 95% confidence intervals for risk of prostate cancer during follow-up through 2014, comparing parenchyma volume tertiles. Results: There was a positive association between pineal parenchyma volume and urinary levels of melatonin. During follow-up, 135 men were diagnosed with prostate cancer, 30 of which were advanced prostate cancer. Men with volumes in the upper tertile had no statistically significant increased risk of prostate cancer compared to men with volumes in the lowest tertile (HR: 1.0, 95% CI: 0.7, 1.5), and men with volumes in the middle tertile had only a borderline statistically significant decreased risk of prostate cancer compared to men with volumes in the lowest tertile (HR: 0.7, 95% CI: 0.4, 1.0). Compared to men without pineal cysts, there was a borderline statistically significant association between men with pineal cysts and decreased risk of prostate cancer (HR: 0.7, 95% CI: 0.5, 1.0). Compared to men without pineal calcifications, there was no statistically significant association between men with pineal calcifications and increased risk of prostate cancer (HR: 1.1, 95% CI: 0.7, 1.6). Conclusions: Pineal parenchyma volume was associated with melatonin levels, but there was no statistically significant association between parenchyma volume alone and prostate cancer risk. Further studies are needed to investigate the relationship between pineal parenchyma volume, presence of calcifications and cysts, melatonin, and prostate cancer. Citation Format: Latifa A. Bazzi, Lara Sigurdardottir, Sigurdur Sigurdsson, Unnur Valdimarsdottir, Johanna Torfadottir, Thor Aspelund, Lenore Launer, Tamara Harris, Vilmundur Gudnason, Lorelei Mucci, Sarah Markt. Pineal gland volume and risk of prostate cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 5045.
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