Background

Prostate cancer is the second most common male cancer worldwide, but there is substantial geographical variation, suggesting a potential role for modifiable risk factors in prostate carcinogenesis.

Methods

We identified previously reported prostate cancer risk factors from the World Cancer Research Fund (WCRF)’s systematic appraisal of the global evidence (2018). We assessed whether each identified risk factor was causally associated with risk of overall (79 148 cases and 61 106 controls) or aggressive (15 167 cases and 58 308 controls) prostate cancer using Mendelian randomization (MR) based on genome-wide association-study summary statistics from the PRACTICAL and GAME-ON/ELLIPSE consortia. We assessed evidence for replication in UK Biobank (7844 prostate-cancer cases and 204 001 controls).

Results

WCRF identified 57 potential risk factors, of which 22 could be instrumented for MR analyses using single nucleotide polymorphisms. For overall prostate cancer, we identified evidence compatible with causality for the following risk factors (odds ratio [OR] per standard deviation increase; 95% confidence interval): accelerometer-measured physical activity, OR = 0.49 (0.33–0.72; P = 0.0003); serum iron, OR = 0.92 (0.86–0.98; P = 0.007); body mass index (BMI), OR = 0.90 (0.84–0.97; P = 0.003); and monounsaturated fat, OR = 1.11 (1.02–1.20; P = 0.02). Findings in our replication analyses in UK Biobank were compatible with our main analyses (albeit with wide confidence intervals). In MR analysis, height was positively associated with aggressive-prostate-cancer risk: OR = 1.07 (1.01–1.15; P = 0.03).

Conclusions

The results for physical activity, serum iron, BMI, monounsaturated fat and height are compatible with causality for prostate cancer. The results suggest that interventions aimed at increasing physical activity may reduce prostate-cancer risk, although interventions to change other risk factors may have negative consequences on other diseases.

中文翻译：

---

评估饮食、营养和体力活动暴露与总体和侵袭性前列腺癌的因果关系：基于 79 148 例前列腺癌病例和 61 106 例对照的两样本孟德尔随机化研究。

 背景

前列腺癌是全球第二常见的男性癌症，但存在很大的地理差异，这表明可改变的危险因素在前列腺癌发生中具有潜在作用。

 方法

我们从世界癌症研究基金会 (WCRF) 对全球证据的系统评估（2018 年）中确定了之前报告的前列腺癌风险因素。我们使用基于全基因组关联研究的孟德尔随机化 (MR) 评估了每个确定的风险因素是否与总体风险（79 148 例病例和 61 106 例对照）或侵袭性前列腺癌（15 167 例病例和 58 308 例对照）风险存在因果关系。来自 PRACTICAL 和 GAME-ON/ELLIPSE 联盟的汇总统计数据。我们评估了英国生物库中的复制证据（7844 例前列腺癌病例和 204 001 例对照）。

 结果

WCRF 确定了 57 种潜在风险因素，其中 22 种可利用单核苷酸多态性进行 MR 分析。对于整体前列腺癌，我们确定了与以下风险因素的因果关系相一致的证据（每标准差增加的比值比 [OR]；95% 置信区间）：加速度计测量的体力活动，OR = 0.49 (0.33–0.72；P = 0.0003 ）；血清铁，OR = 0.92（0.86–0.98；P = 0.007）；体重指数 (BMI)，OR = 0.90 (0.84–0.97；P = 0.003)；和单不饱和脂肪，OR = 1.11 (1.02–1.20；P = 0.02)。我们在英国生物银行的复制分析结果与我们的主要分析一致（尽管置信区间很宽）。在 MR 分析中，身高与侵袭性前列腺癌风险呈正相关：OR = 1.07 (1.01–1.15；P = 0.03)。

 结论

身体活动、血清铁、体重指数、单不饱和脂肪和身高的结果与前列腺癌的因果关系一致。结果表明，旨在增加体力活动的干预措施可能会降低前列腺癌的风险，尽管改变其他危险因素的干预措施可能会对其他疾病产生负面影响。