Metabolomic Analysis of Renal Cell Carcinoma in the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial

Abstract

Background: In the US in 2021, 76,080 kidney cancers are expected and >80% are renal cell carcinomas (RCCs). Along with excess fat, metabolic dysfunction is implicated in RCC etiology. To identify RCC-associated metabolites, we conducted a 1:1 matched case–control study nested within the Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial. Methods: We measured 522 serum metabolites in 267 cases/control pairs. Cases were followed for a median 7.1 years from blood draw to diagnosis. Using conditional logistic regression, we computed adjusted odds ratios (ORs) and 95% confidence intervals (CIs) comparing risk between 90th and 10th percentiles of log metabolite intensity, with the significance threshold at a false discovery rate <0.20. Results: Four metabolites were inversely associated with risk of RCC during follow-up—C38:4 PI, C34:0 PC, C14:0 SM, and C16:1 SM (ORs ranging from 0.33–0.44). Two were positively associated with RCC risk—C3-DC-CH3 carnitine and C5 carnitine (ORs = 2.84 and 2.83, respectively). These results were robust when further adjusted for metabolic risk factors (body mass index (BMI), physical activity, diabetes/hypertension history). Metabolites associated with RCC had weak correlations (|r| < 0.2) with risk factors of BMI, physical activity, smoking, alcohol, and diabetes/hypertension history. In mutually adjusted models, three metabolites (C38:4 PI, C14:0 SM, and C3-DC-CH3 carnitine) were independently associated with RCC risk. Conclusions: Serum concentrations of six metabolites were associated with RCC risk, and three of these had independent associations from the mutually adjusted model. These metabolites may point toward new biological pathways of relevance to this malignancy.

Influence of Dietary Polyunsaturated Fatty Acid Intake on Potential Lipid Metabolite Diagnostic Markers in Renal Cell Carcinoma: A Case-Control Study

“…Dysregulation of these pathways is linked to cellular metabolism reprogramming, supporting tumor-cell survival [48]. Our findings highlight alterations in TCA metabolism, impaired mitochondrial bioenergetics, and oxidative phosphorylation in RCC [49], underscoring the role of lipid and amino acid metabolism in carcinogenesis.…”

Fisiologia Do Esporte: O Uso De Esteroides Anabolizantes

“…Inicialmente, os esteroides anabolizantes foram desenvolvidos com propósitos terapêuticos e, em algumas situações médicas específicas, são administrados para repor a deficiência de testosterona em pacientes que apresentam déficits hormonais devido a condições patológicas (DE OLIVEIRA FERREIRA et al, 2023) Além disso, em doses terapêuticas controladas, esses esteroides são utilizados no tratamento de diversas condições clínicas, como AIDS, hipogonadismo, puberdade anormal, certos tipos de câncer, desnutrição (para estimular o apetite), deficiências hormonais, osteoporose, alguns tipos de anemia, disfunção erétil, castração e baixa estatura devido à síndrome de Turner (WILLEMS et al, 2023;PEZZAIOLI et al, 2022;LIM et al, 2023;DE OLIVEIRA FERREIRA et al, 2023). Portanto, além do seu uso inadequado para ganho de massa muscular, os EAA desempenham um papel importante na terapia médica de várias condições clínicas, sob rigorosa supervisão profissional.…”

Adiposity and cancer: meta-analysis, mechanisms, and future perspectives

“…metabolites associated with both BMI and breast cancer risk-included asparagine and phosphatidylcholines with 34 to 36 carbon atoms 155,157 . For kidney cancer, C3-DC-CH3 carnitine and C5 carnitine were estimated to mediate 20% of the BMI-kidney cancer association 163 and suggestive evidence was found for several phosphatidylcholines 164 . Lastly, a large European study of eight cancer types (breast cancer, colorectal cancer, endometrial cancer, kidney cancer, gallbladder cancer, liver cancer, advanced prostate cancer and localised prostate cancer) found nine metabolites/metabolite clusters robustly associated with cancer risk, including the BMI-associated metabolites of 36-carbon phosphatidylcholines, glutamine, and butyrylcarnitine 165 .…”