Investigating the association between spermidine and renal cell carcinoma
Within the several RCC risk factors identified, smoking, obesity, and hypertension are most strongly associated with RCC. Potential risk factors include behavioural and environmental factors, comorbidities, and analgesics.
Dietary polyamine uptake correlates with reduced cardiovascular and cancer-related mortality in human epidemiological studies[5]. Spermidine, as a natural component from polyamine members, is originally isolated from semen and also existed in many natural plants.Spermidine preserves mitochondrial function, exhibits anti-inflammatory properties, and prevents stem cell senescence. The natural mammalian polyamines putrescine, spermidine and spermine are essential for both normal and neoplastic cell function and replication. While polyamines, polyamine metabolism, the microbiota and the diet were found to interconnect to establish a tumour microenvironment that facilitates the initiation and progression of cancer[6]. Increased intake of polyamine seems to suppress tumorigenesis, but appears to accelerate the growth of established tumors. [7]
Because spermidine is already present in daily human nutrition, a study which aims to determine the association between spermidine intake and RCC or other cancers’risks and to examine whether this association is modified by factors such as BMI,smoking, hypertension ,alchol consumption, family history, is feasible.
[1] Sung H, Ferlay J, Siegel RL, et al. Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin 2021;71:209–49
[2] Moch H, Cubilla AL, Humphrey PA, Reuter VE, Ulbright TM. The 2016 WHO classification of tumours of the urinary system and male genital organs—part A: renal, penile, and testicular tumours. Eur Urol 2016;70:93–105
[3] Siegel RL, Miller KD, Jemal A. Cancer statistics, 2018. CA Cancer J Clin 2018;68:7–30.
[4] Ferlay J, Soerjomataram I, Ervik M, et al. GLOBOCAN 2012 v1.0, Cancer incidence and mortality worldwide: IARC CancerBase No. 11. Lyon, France: International Agency for Research on Cancer; 2013
[5] Madeo F, Eisenberg T, Pietrocola F, Kroemer G. Spermidine in health and disease. Science. 2018 Jan 26;359(6374):eaan2788. doi: 10.1126/science.aan2788. PMID: 29371440.
[6] Holbert CE, Cullen MT, Casero RA Jr, Stewart TM. Polyamines in cancer: integrating organismal metabolism and antitumour immunity. Nat Rev Cancer. 2022 Aug;22(8):467-480. doi: 10.1038/s41568-022-00473-2. Epub 2022 Apr 27. PMID: 35477776; PMCID: PMC9339478.
[7] Fan J, Feng Z, Chen N. Spermidine as a target for cancer therapy. Pharmacol Res. 2020 Sep;159:104943. doi: 10.1016/j.phrs.2020.104943. Epub 2020 May 24. PMID: 32461185.
1. Assess the association between spermidine (And other biomarkers that may be associated) and RCC or other cancers’ risks.Subgroup analysis to explore whether the association between spermidine (And other biomarkers that may be associated) and risk of RCC differs by BMI, smoking status, alcohol consumption, family history, etc.
2.Apply dose-response analysis to examine the relationship between spermidine (And other biomarkers that may be associated) and the incidence of RCC.
3. Develop a novel RCC risk prediction model among the RCC cases and their matched controls.
4. Using machine learning algorithms to select the best dietary combinations to prevent RCC.
Our long-term goal is thus to reduce the burden of RCC, a significantly disparate and often fatal disease in the US. We hope to provide evidence for spermidine to prevent cancer and put forward the idea of future clinical application.
Qingquan Chen, Kang Yang, Jiajing Zhuang,Ling Yao(Fujian Medical University, Fuzhou)