School of Clinical Medicine, Peking University China-Japan Friendship, Beijing, China.
China-Japan Friendship Hospital, Yinghuadong Road, Chaoyang District, Beijing, 100029, China.
Eur J Nutr. 2023 Sep;62(6):2365-2373. doi: 10.1007/s00394-023-03158-0. Epub 2023 Apr 26.
In previous observational studies, food-derived antioxidant vitamins have been suggested to be associated with breast cancer. However, the findings were inconsistent and the causal relationship could not be clearly elucidated. To confirm the potential causal relationship between food-derived antioxidants (retinol, carotene, vitamin C and vitamin E) and the risk of breast cancer, we conducted a two-sample Mendelian randomization (MR) study.
The instrumental variables (IVs) as proxies of genetic liability to food-derived antioxidant vitamins were obtained from the UK Biobank Database. We extracted breast cancer data (122,977 cases and 105,974 controls) from the Breast Cancer Consortium (BCAC). In addition, we studied estrogen expression status categorically, including estrogen receptor positive (ER) breast cancer (69,501 cases and 105,974 controls) and versus estrogen receptor (ER) negative breast cancer (21,468 cases and 105,974 controls). We performed two-sample Mendelian randomization study, and inverse variance-weighted (IVW) test was regarded as main analysis. Sensitivity analyses were further conducted to assess heterogeneity and horizontal pleiotropy.
The results of IVW showed that among the four food-derived antioxidants, only vitamin E had protective effect on the risk of overall breast cancer (OR = 0.837, 95% CI 0.757-0.926, P = 0.001) and ER breast cancer (OR = 0.823, 95% CI 0.693-0.977, P = 0.026). However, we found no association between food-derived vitamin E and ER breast cancer.
Our study suggested food-derived vitamin E can decrease the risk of breast cancer overall and ER breast cancer, and the robustness of our results was confirmed by sensitivity analyses.
在之前的观察性研究中,食物来源的抗氧化维生素与乳腺癌之间存在关联。然而,研究结果并不一致,因果关系也无法明确阐明。为了证实食物来源的抗氧化剂(视黄醇、类胡萝卜素、维生素 C 和维生素 E)与乳腺癌风险之间的潜在因果关系,我们进行了两样本 Mendelian 随机化(MR)研究。
作为食物来源的抗氧化维生素遗传易感性的工具变量(IVs),我们从英国生物银行数据库中获得。我们从乳腺癌联盟(BCAC)中提取乳腺癌数据(122977 例病例和 105974 例对照)。此外,我们还对雌激素表达状态进行了分类研究,包括雌激素受体阳性(ER)乳腺癌(69501 例病例和 105974 例对照)和雌激素受体阴性(ER)乳腺癌(21468 例病例和 105974 例对照)。我们进行了两样本 Mendelian 随机化研究,将逆方差加权(IVW)检验作为主要分析方法。进一步进行敏感性分析以评估异质性和水平多效性。
IVW 的结果表明,在四种食物来源的抗氧化剂中,只有维生素 E 对整体乳腺癌(OR=0.837,95%CI 0.757-0.926,P=0.001)和雌激素受体阳性乳腺癌(OR=0.823,95%CI 0.693-0.977,P=0.026)的风险具有保护作用。然而,我们没有发现食物来源的维生素 E 与雌激素受体阳性乳腺癌之间存在关联。
我们的研究表明,食物来源的维生素 E 可以降低整体乳腺癌和雌激素受体阳性乳腺癌的风险,并且敏感性分析证实了我们结果的稳健性。