The controversy regarding the causal relationship between circulating glutamine and cancer risk remains unresolved. Here, we aim to assess the causal impact of glutamine on the risk of six prevalent cancer types and their respective subtypes including breast, lung, ovarian, thyroid, prostate, and endometrial cancers. A Mendelian randomization (MR) analysis was conducted to evaluate the causal effect of circulating glutamine on cancers risk. Data on circulating glutamine were extracted from the UK Biobank (UKB), comprising 114,750 European patients. To ensure the validity of our findings, we employed several analytical approaches, such as inverse variance weighting, weighted median, weighted mode test, MR-Egger regression, and MR-PRESSO method. Both univariable and multivariable MR analyses were conducted. Additionally, we employed a large-scale summary-level study on circulating glutamine involving 24,925 European participants for validation purposes. Our MR analysis reveals a causal association between circulating glutamine and thyroid cancer in both the UKB cohort (IVW: OR = 0.667, 95% CI [0.541-0.822], P = 1.52×10-4) and the validated cohort (IVW: OR = 0.577, 95% CI [0.421-0.790], P = 6.14×10-4). Sensitivity analysis, including multivariable MR analyses, consistently supports this finding (P < 0.05), affirming the reliability and robustness of our study. Our findings indicate an inverse correlation between circulating glutamine and the incidence of thyroid cancer in European populations. However, further research encompassing diverse ancestries is necessary to validate this causal relationship.
Keywords: Circulating glutamine; GWAS; Mendelian randomization; UK Biobank; cancer; genetics.
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