Abstract 2207: Fiber intake and risk of lethal prostate cancer among men at increased genetic risk

Abstract Introduction High fiber intake from grains may lower advanced prostate cancer risk by enhancing insulin sensitivity, lowering insulin-like growth factor 1 and systemic inflammation. Whether a high-fiber diet can lower risk of metastatic disease and prostate cancer death in men at high genetic risk is unclear. Methods Using a new 400-SNP polygenic risk score (PRS) for prostate cancer, we quantified the genetic risk of 10,269 men with available genotype data in the Health Professionals Follow-up Study, followed between 1993 and 2019. Men in the top 50-100% PRS category were considered high-risk and included for analysis. Total fiber intake and different sources (cereal, fruits, vegetables) were assessed by validated food frequency questionnaires. Overall and lethal prostate cancer (metastatic disease/prostate cancer death) were analyzed using Cox proportional hazards models estimating hazard ratios (HRs) and 95% confidence intervals (CIs). Results During 26 years of follow-up, we recorded 1,494 overall and 174 lethal prostate cancer events in the high genetic risk group. As expected, no associations were observed fiber intake with risk of overall prostate cancer. For lethal prostate cancer, the results varied according to the source of fiber. Higher cereal fiber intake was associated with a lower risk of lethal prostate cancer (per 3 g/d higher intake: 0.81 [0.68, 0.97], P-trend=0.02). We further observed a higher disease risk among men with higher fruit fiber intake (per 3g/d higher intake: 1.18 [1.02, 1.36], P-trend=0.03). The associations remained similar when mutually adjusted for each fiber type. No associations were observed for total or vegetable fiber intake. Conclusion In this analysis of men at high prostate cancer genetic risk, we observed that higher cereal fiber intake was associated with lower lethal prostate cancer risk, whereas higher fruit fiber intake showed an opposite trend. Further studies in different populations and investigations into the underlying mechanisms are needed. Fiber intake with risk of overall and lethal prostate cancer among men at high genetic risk. Fiber type Overall prostate cancer: No.event/PY Overall prostate cancer: HR (95% CI) Lethal prostate cancer: No.event/PY Lethal prostate cancer: HR (95% CI) All fiber, g/d T1, median=15.8 490/66047 ref. 42/73826 ref. T2, median=21.8 484/62237 0.96 (0.83-1.11) 61/69849 1.16 (0.77-1.75) T3, median=29.9 520/67374 1.02 (0.86-1.21) 71/75242 1.24 (0.75-2.05) Per 3 g/d 0.98 (0.96-1.01) 1.00 (0.92-1.08) P for trend 0.27 0.93 Cereal fiber, g/d T1, median=4.6 491/63911 ref. 49/72367 ref. T2, median=6.7 512/66251 1.04 (0.91-1.20) 76/73384 1.30 (0.90-1.87) T3, median=9.4 491/65496 0.92 (0.80-1.06) 49/73166 0.75 (0.50-1.12) Per 3 g/d 0.96 (0.90-1.01) 0.81 (0.68-0.97) P for trend 0.14 0.02 Fruit fiber, g/d T1, median=2.5 471/66306 ref. 33/74056 ref. T2, median=4.5 514/63268 1.06 (0.92-1.22) 51/70430 1.21 (0.76-1.91) T3, median=7.2 509/66085 1.00 (0.86-1.16) 90/74431 1.84 (1.18-2.87) Per 3 g/d 0.97 (0.91-1.03) 1.18 (1.02-1.36) P for trend 0.34 0.03 Vegetable fiber, g/d T1, median=4.8 481/64139 ref. 51/71594 ref. T2, median=6.9 505/64938 1.04 (0.91-1.20) 66/72291 1.22 (0.84-1.78) T3, median=9.6 508/66581 1.04 (0.90-1.20) 57/75031 0.98 (0.65-1.45) Per 3 g/d 0.99 (0.93-1.05) 0.97 (0.82-1.15) P for trend 0.72 0.74 Citation Format: Yiwen Zhang, Konrad H. Stopsack, Lorelei A. Mucci, Edward Giovannucci, Anna Plym. Fiber intake and risk of lethal prostate cancer among men at increased genetic risk [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 2207.