Statistical Genetics Laboratory, QIMR Berghofer Medical Research Institute, Herston, Australia.
Cancer Epidemiol Biomarkers Prev. 2019 Jun;28(6):1015-1023. doi: 10.1158/1055-9965.EPI-18-0940. Epub 2019 Apr 4.
Observational studies evaluating the link between polyunsaturated fatty acids (PUFA) and cancers have yielded mixed findings. We used Mendelian randomization (MR) to evaluate whether genetic evidence supports a causal role for PUFAs on overall cancer outcomes.
We identified genetic instruments for six PUFAs from previous literature and evaluated their association with overall cancer risk (46,155 cases, 270,342 controls) and cancer mortality (6,998 deaths, 270,342 controls) among the UK Biobank cohort. We used the inverse variance weighted model to combine SNP estimates, and derived log (OR) estimates per SD change in each PUFA.
None of the six PUFAs showed association with overall cancer risk or mortality, with narrow confidence interval (CI) ruling out all but very small effects, for example, arachidonic acid (AA) overall cancer risk (OR, 1.02; 95% CI, 1.00-1.03). Sex-specific analysis revealed no associations except α-linolenic acid for potentially reducing cancer risk in men (OR, 0.92; 95% CI, 0.86-0.98; = 0.02); however, this was nonsignificant after multiple testing correction. From individual cancers, only colorectal cancer showed evidence for a causal association for higher AA levels (OR, 1.05; 95% CI, 1.03-1.07), with similar results for the other correlated PUFAs.
Our study provides no support for the hypothesis that PUFAs reduce overall cancer risk or mortality. Higher AA levels increased the risk for colorectal cancer.
Our well-powered MR study provides robust causal inferences for the PUFAs on overall cancer risk and mortality. Future larger studies are warranted to replicate the individual cancer findings.
评估多不饱和脂肪酸（PUFA）与癌症之间关联的观察性研究得出的结果不一。我们使用孟德尔随机化（MR）来评估遗传证据是否支持 PUFAs 对整体癌症结局的因果作用。
我们从先前的文献中确定了六种 PUFAs 的遗传工具，并在英国生物银行队列中评估了它们与总体癌症风险（46155 例病例，270342 例对照）和癌症死亡率（6998 例死亡，270342 例对照）之间的关系。我们使用逆方差加权模型来合并 SNP 估计值，并得出每种 PUFA 每标准差变化的对数（OR）估计值。
六种 PUFAs 中没有一种与总体癌症风险或死亡率相关，置信区间较窄（CI）排除了除非常小的影响之外的所有影响，例如，花生四烯酸（AA）的总体癌症风险（OR，1.02；95%CI，1.00-1.03）。性别特异性分析显示，除了α-亚麻酸（ALA）可能降低男性患癌症的风险（OR，0.92；95%CI，0.86-0.98；P=0.02）外，没有其他关联；然而，在多次测试校正后，这一关联不再显著。从个别癌症来看，只有结直肠癌显示出 AA 水平升高与癌症风险增加之间存在因果关系（OR，1.05；95%CI，1.03-1.07），其他相关 PUFAs 也有类似的结果。
我们的研究不支持 PUFAs 降低总体癌症风险或死亡率的假设。较高的 AA 水平增加了结直肠癌的风险。
我们这项有力的 MR 研究为 PUFAs 对总体癌症风险和死亡率提供了可靠的因果推断。未来需要更大的研究来复制个别癌症的发现。
