Yang Shaoxue, Song Jie, Yang Hong, Liu Wei, Jiang Yuqing, Sun Xiaohui, Ye Ding, Xu Songxiao, Mao Yingying
The Cancer Hospital of the University of Chinese Academy of Sciences (Zhejiang Cancer Hospital), Institute of Basic Medicine and Cancer (IBMC), Hangzhou, 310022, People's Republic of China.
Department of Epidemiology, Zhejiang Chinese Medical University School of Public Health, Hangzhou, 310053, People's Republic of China.
Clin Epidemiol. 2022 Oct 28;14:1255-1264. doi: 10.2147/CLEP.S382116. eCollection 2022.
Prostate cancer is one of the leading malignancies in men worldwide. Previous observational studies have linked amino acids and transaminase with altered risk of prostate cancer. However, whether these associations were causal remained unclear. Therefore, we conducted a Mendelian randomization (MR) to assess their potential causal associations.
Summary-level data for prostate cancer were obtained from a meta-analysis of genome-wide association studies (GWAS) including 79,148 prostate cancer cases and 61,106 controls of European descent. Instrumental variables (IVs) of amino acids and alanine aminotransferase (ALT) were obtained from a GWAS of 86,507 European individuals and a GWAS of 312,572 participants from the UK Biobank, respectively. MR analyses were performed using inverse-variance-weighted (IVW), likelihood-based, MR Pleiotropy RESidual Sum and Outlier (MR-PRESSO) test and MR-Egger regression.
Genetically predicted circulating concentrations of alanine were associated with an increased risk of prostate cancer (odds ratio (OR): 1.16, 95% confidence interval (CI): 1.01-1.33, =0.037 by IVW). Consistently, genetically predicted ALT was inversely associated with the risk of prostate cancer (OR: 0.43, 95% CI: 0.27-0.68, =3.28×10 by IVW). MR-Egger regression did not indicate evidence of directional pleiotropy and sensitivity analyses yielded consistent associations.
Our study revealed that genetically predicted circulating alanine and ALT levels were associated with an altered risk of prostate cancer, suggesting their potential roles in the development of prostate cancer. Whether targeting alanine, ALT or its downstream effectors are helpful in reducing prostate cancer incidence warrants further investigation.
前列腺癌是全球男性主要的恶性肿瘤之一。既往观察性研究已将氨基酸和转氨酶与前列腺癌风险改变联系起来。然而，这些关联是否为因果关系仍不明确。因此，我们进行了一项孟德尔随机化（MR）研究以评估它们潜在的因果关联。
前列腺癌的汇总水平数据来自一项全基因组关联研究（GWAS）的荟萃分析，包括79148例前列腺癌病例和61106例欧洲血统对照。氨基酸和丙氨酸转氨酶（ALT）的工具变量（IVs）分别来自一项对86507名欧洲个体的GWAS和一项来自英国生物银行的312572名参与者的GWAS。使用逆方差加权（IVW）、基于似然性的、MR多效性残差和异常值（MR-PRESSO）检验以及MR-Egger回归进行MR分析。
基因预测的循环丙氨酸浓度与前列腺癌风险增加相关（优势比（OR）：1.16，95%置信区间（CI）：1.01-1.33，IVW法P=0.037）。同样，基因预测的ALT与前列腺癌风险呈负相关（OR：0.43，95%CI：0.27-0.68，IVW法P=3.28×10）。MR-Egger回归未表明存在定向多效性证据，敏感性分析得出了一致的关联。
我们的研究表明，基因预测的循环丙氨酸和ALT水平与前列腺癌风险改变相关，提示它们在前列腺癌发生发展中的潜在作用。靶向丙氨酸、ALT或其下游效应器是否有助于降低前列腺癌发病率值得进一步研究。
