Genetically Predicted Circulating Concentrations of Alanine and Alanine Aminotransferase Were Associated with Prostate Cancer Risk

Yang, Shaoxue; Song, Jié; Yang, Hong; Liu, Wei; Jiang, Yuqing; Sun, Xiaohui; Ye, Ding; Xu, Songxiao; Mao, Yingying

doi:10.2147/clep.s382116

Cited by 3 publications

(1 citation statement)

References 39 publications

(46 reference statements)

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“…It is not known whether amino acids in the blood are a risk factor for colon adenocarcinoma. Genetically predicted circulating alanine and ALT levels have been associated with altered prostate cancer risk in an MR study [ 16 ].…”

Section: Discussionmentioning

confidence: 99%

Amino acids and risk of colon adenocarcinoma: a Mendelian randomization study

Wang,

Jia,

Wang

et al. 2023

BMC Cancer

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Background The existence of amino acid metabolic reprogramming in tumor cells is well established. However, the potential correlation between blood amino acids and the risk of colon adenocarcinoma remains largely unexplored. Methods We utilized Mendelian randomization (MR) analysis to examine the association between 20 amino acids in the blood and the risk of colon adenocarcinoma. Additionally, reverse MR analysis was employed to identify the presence of reverse causality. A two-step MR analysis was conducted to ascertain the potential mediating effect. Lastly, the alanine detection data from colon adenocarcinoma patients in our hospital were utilized to investigate the differences in alanine levels among healthy individuals and patients with colon cancer, as well as among patients with different stages and locations of colon cancer. Furthermore, a Kaplan–Meier curve was employed to examine the correlation between alanine and overall survival, followed by the implementation of COX univariate analysis. Results The results of our study indicate that there is an inverse correlation between alanine and the risk of colon adenocarcinoma. Additionally, we found no significant evidence to support a causal relationship between colon adenocarcinoma and alanine. Furthermore, our analysis revealed that alanine aminotransferase (ALT) and blood glucose do not act as mediators in this causal pathway. Moreover, individuals diagnosed with colon adenocarcinoma exhibited a significant decrease in alanine levels, particularly in cases of stage IV colon adenocarcinoma with distant metastasis. Additionally, elevated alanine levels were associated with improved overall survival rates among colon adenocarcinoma patients. Conclusions The results of this study indicate that alanine exhibits protective characteristics against the onset of colon adenocarcinoma and may play a role in promoting a more favorable disease prognosis. Consequently, dietary interventions aimed at increasing alanine intake may serve as a potential strategy for the prevention and treatment of colon adenocarcinoma.

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Section: Discussionmentioning

confidence: 99%

Amino acids and risk of colon adenocarcinoma: a Mendelian randomization study

Wang,

Jia,

Wang

et al. 2023

BMC Cancer

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Risk factors for prostate cancer: An umbrella review of prospective observational studies and mendelian randomization analyses

Cui,

Zhang,

Zhang

et al. 2024

PLoS Med

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Background The incidence of prostate cancer is increasing in older males globally. Age, ethnicity, and family history are identified as the well-known risk factors for prostate cancer, but few modifiable factors have been firmly established. The objective of this study was to identify and evaluate various factors modifying the risk of prostate cancer reported in meta-analyses of prospective observational studies and mendelian randomization (MR) analyses. Methods and findings We searched PubMed, Embase, and Web of Science from the inception to January 10, 2022, updated on September 9, 2023, to identify meta-analyses and MR studies on prostate cancer. Eligibility criteria for meta-analyses were (1) meta-analyses including prospective observational studies or studies that declared outcome-free at baseline; (2) evaluating the factors of any category associated with prostate cancer incidence; and (3) providing effect estimates for further data synthesis. Similar criteria were applied to MR studies. Meta-analysis was repeated using the random-effects inverse-variance model with DerSimonian—Laird method. Quality assessment was then conducted for included meta-analyses using AMSTAR-2 tool and for MR studies using STROBE-MR and assumption evaluation. Subsequent evidence grading criteria for significant associations in meta-analyses contained sample size, P values and 95% confidence intervals, 95% prediction intervals, heterogeneity, and publication bias, assigning 4 evidence grades (convincing, highly suggestive, suggestive, or weak). Significant associations in MR studies were graded as robust, probable, suggestive, or insufficient considering P values and concordance of effect directions. Finally, 92 selected from 411 meta-analyses and 64 selected from 118 MR studies were included after excluding the overlapping and outdated studies which were published earlier and contained fewer participants or fewer instrument variables for the same exposure. In total, 123 observational associations (45 significant and 78 null) and 145 causal associations (55 significant and 90 null) were categorized into lifestyle; diet and nutrition; anthropometric indices; biomarkers; clinical variables, diseases, and treatments; and environmental factors. Concerning evidence grading on significant associations, there were 5 highly suggestive, 36 suggestive, and 4 weak associations in meta-analyses, and 10 robust, 24 probable, 4 suggestive, and 17 insufficient causal associations in MR studies. Twenty-six overlapping factors between meta-analyses and MR studies were identified, with consistent significant effects found for physical activity (PA) (occupational PA in meta: OR = 0.87, 95% CI: 0.80, 0.94; accelerator-measured PA in MR: OR = 0.49, 95% CI: 0.33, 0.72), height (meta: OR = 1.09, 95% CI: 1.06, 1.12; MR: OR = 1.07, 95% CI: 1.01, 1.15, for aggressive prostate cancer), and smoking (current smoking in meta: OR = 0.74, 95% CI: 0.68, 0.80; smoking initiation in MR: OR = 0.91, 95% CI: 0.86, 0.97). Methodological limitation is that the evidence grading criteria could be expanded by considering more indices. Conclusions In this large-scale study, we summarized the associations of various factors with prostate cancer risk and provided comparisons between observational associations by meta-analysis and genetically estimated causality by MR analyses. In the absence of convincing overlapping evidence based on the existing literature, no robust associations were identified, but some effects were observed for height, physical activity, and smoking.

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Association between circulating alanine and cancer susceptibility using Mendelian randomization

Cai

Liu

Lin

et al. 2023

Preprint

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Background Circulating alanine concentrations are associated with several cancers, but little is known about the causal direction of the associations. This study aims to explore whether there is a relationship between circulating alanine and ten common cancers. Methods We conducted two-sample Mendelian randomization (MR) analysis to assess the causal effects of circulating alanine on ten common cancers. According to published genome-wide association studies (GWASs), we obtained 36 alanine-related single nucleotide polymorphisms used as instrumental variables. For exposure data, genetic association data of lung, breast, pancreatic, liver, colorectal, esophageal, stomach, thyroid, prostate and ovarian cancer from GWAS Consortia were used, including up to 1,213,351 participants of European origin and 196,187 participants of East Asian. The inverse variance weighting (IVW) method was used for MR analysis, and MR-Egger and the weighted median method further evaluated the pleiotropic effect. Results Specific to cancer GWAS, we found that circulating alanine was significantly associated with increased squamous cell lung cancer (odds ratio [OR]: 1.37, 95% CI = 1.00-1.87; P = 0.048), pancreatic cancer (OR 3.02, 95% CI = 1.35 to 6.76; P = 0.007), low grade serous ovarian cancer (OR 1.81, 95% CI = 1.01 to 3.25; P = 0.047). We have no evidence of a convincing causal effect of circulating alanine concentrations predicted by genetics on other cancer risks. Conclusion We observed the possible causal relationship between circulating alanine and lung squamous cell carcinoma, pancreatic cancer, low-grade serial ovarian cancer. Further research is needed to verify this causal relationship.

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Genetically Predicted Circulating Concentrations of Alanine and Alanine Aminotransferase Were Associated with Prostate Cancer Risk

Cited by 3 publications

References 39 publications

Amino acids and risk of colon adenocarcinoma: a Mendelian randomization study

Amino acids and risk of colon adenocarcinoma: a Mendelian randomization study

Risk factors for prostate cancer: An umbrella review of prospective observational studies and mendelian randomization analyses

Association between circulating alanine and cancer susceptibility using Mendelian randomization

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