Shu Xinru, Lin Jiayi, Yao Ling, Liu Shun, Chen Qingquan, Wang Honggeng, Wang Liangming
The Second Affiliated Hospital of Fujian Medical University, Quanzhou, Fujian Province, China.
Fujian Medical University, Fuzhou, China.
Front Nutr. 2025 Jul 21;12:1623295. doi: 10.3389/fnut.2025.1623295. eCollection 2025.
Prostate cancer is the second most prevalent malignant cancer globally and the fifth leading cause of cancer-related mortality. Omega-3 PUFAs [including eicosapentaenoic acid (EPA), docosapentaenoic acid (DPA), and docosahexaenoic acid (DHA)] may mitigate prostate cancer risk through various molecular mechanisms, such as inhibiting pro-inflammatory eicosanoid production via COX-2 pathway, regulating apoptosis and autophagy, and potentially influencing other signaling pathways like NF-κB. However, existing studies have reported inconsistent findings regarding the effects of Omega-3 fatty acids on prostate cancer, and there is limited large-scale longitudinal data exploring the dose-response relationship.
This study utilized data from the Prostate, Lung, Colorectal, and Ovarian (PLCO) Screening Trial to investigate the associations between Omega-3 (EPA, DPA, DHA) intake from dietary sources and the risk of prostate cancer and mortality. Omega-3 fatty acid intake was assessed via the Dietary History Questionnaire (DHQ). Multivariate Cox proportional hazards regression models, adjusted for key confounders including age, race, BMI, family history, PSA levels, comorbidities, and lifestyle factors, were employed alongside restricted cubic spline (RCS) analysis to account for potential confounding factors. A total of 30,552 male participants aged 55-74 years were included, with a median follow-up time of ≥7 years.
The results indicated a linear relationship between Omega-3 fatty acid intake and the overall risk of prostate cancer (HR for highest vs. lowest quintile: 0.90, 95% CI: 0.81-1.00, = 0.053). For prostate cancer mortality, a non-linear relationship was observed ( = 0.009). The risk of death decreased as intake increased below 0.4 g/d, with a hazard ratio of 0.67 (95% CI: 0.49-0.91, = 0.011) for the second quintile compared to the lowest quintile. However, intake exceeding this threshold was associated with an increased risk (HR for highest quintile: 0.70, 95% CI: 0.52-0.95, = 0.021). The RCS analysis revealed a potential U-shaped association for mortality risk, with the lowest risk corresponding to an intake range of ~0.15-0.40 g/d.
Increased dietary intake of Omega-3 fatty acids has been associated with a reduced risk of prostate cancer. However, the association with mortality risk showed a threshold effect, with intakes below 0.4 g/day reducing mortality and higher intakes potentially increasing risk.
前列腺癌是全球第二大常见恶性肿瘤，也是癌症相关死亡的第五大主要原因。ω-3多不饱和脂肪酸[包括二十碳五烯酸（EPA）、二十二碳五烯酸（DPA）和二十二碳六烯酸（DHA）]可能通过多种分子机制降低前列腺癌风险，如通过COX-2途径抑制促炎类花生酸的产生、调节细胞凋亡和自噬，以及可能影响其他信号通路如NF-κB。然而，现有研究报告了关于ω-3脂肪酸对前列腺癌影响的不一致结果，且探索剂量反应关系的大规模纵向数据有限。
本研究利用前列腺、肺、结肠和卵巢（PLCO）筛查试验的数据，调查饮食来源的ω-3（EPA、DPA、DHA）摄入量与前列腺癌风险及死亡率之间的关联。通过饮食史问卷（DHQ）评估ω-3脂肪酸摄入量。采用多变量Cox比例风险回归模型，并针对包括年龄、种族、体重指数、家族史、前列腺特异性抗原水平、合并症和生活方式因素等关键混杂因素进行调整，同时采用限制性立方样条（RCS）分析来考虑潜在的混杂因素。共纳入30552名年龄在55 - 74岁的男性参与者，中位随访时间≥7年。
结果表明ω-3脂肪酸摄入量与前列腺癌总体风险之间存在线性关系（最高五分位数与最低五分位数相比的风险比：0.90，95%置信区间：0.81 - 1.00，P = 0.053）。对于前列腺癌死亡率，观察到非线性关系（P = 0.009）。当摄入量低于0.4 g/d时，死亡风险随摄入量增加而降低，与最低五分位数相比，第二五分位数的风险比为0.67（95%置信区间：0.49 - 0.91，P = 0.011）。然而，摄入量超过该阈值与风险增加相关（最高五分位数的风险比：0.70，95%置信区间：0.52 - 0.95，P = 0.021）。RCS分析揭示了死亡风险可能呈U形关联，最低风险对应于摄入量约为0.15 - 0.40 g/d的范围。
饮食中ω-3脂肪酸摄入量增加与前列腺癌风险降低相关。然而，与死亡风险的关联显示出阈值效应，摄入量低于0.4 g/天可降低死亡率，而较高摄入量可能增加风险。
