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Xueren Gao School of Pharmacy, Yancheng Teachers' University, Yancheng, China

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Yuqing Chen School of Pharmacy, Yancheng Teachers' University, Yancheng, China

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Abstract

Previous observational studies have investigated the association between urinary albumin excretion and the risk of colorectal cancer (CRC), but the results have been inconsistent. This study aimed to explore the causal association between urine albumin-to-creatinine ratio (ACR) and CRC risk through a two-sample Mendelian randomization (MR) analysis. The genome-wide association study (GWAS) data of ACR (n = 382,500) and CRC (CRC: 6,509 cases and 287,137 controls) were obtained from the IEU OpenGWAS project website and the FinnGen database, respectively. The TwoSampleMR and MR-PRESSO R packages were used to search for and analyze genetic variations that served as instrumental variables for ACR. The odds ratios (ORs) and 95% confidence intervals (95% CIs) were calculated using the inverse-variance weighted method, MR-Egger, and weighted median. Genetically predicted ACR was not associated with CRC risk (all P > 0.05). Further analysis based on the site of onset (colon or rectum) also did not show a significant association (all P > 0.05). MR-PRESSO, MR-Egger regression and leave-one-out sensitivity analysis all indicated that the current results were robust and reliable. These findings suggest that ACR does not affect CRC risk and may not be used as a marker of CRC risk in clinical practice. However, relevant studies especially in ethnically diverse populations are still needed to confirm the current findings.

  • 1.

    Sung H, Ferlay J, Siegel RL, Laversanne M, Soerjomataram I, Jemal A, 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(3): 20949. https://doi.org/10.3322/caac.21660.

    • Search Google Scholar
    • Export Citation
  • 2.

    Rawla P, Sunkara T, Barsouk A. Epidemiology of colorectal cancer: incidence, mortality, survival, and risk factors. Prz Gastroenterol 2021; 14(2): 89103. https://doi.org/10.5114/pg.2018.81072.

    • Search Google Scholar
    • Export Citation
  • 3.

    Dobrowolski P, Januszewicz A, Gumprecht J, Małyszko J, Narkiewicz K, Stompór T, et al. Why albuminuria should be assessed more frequently in everyday clinical practice? A position statement. Pol Arch Intern Med 2021; 131(4): 396406. https://doi.org/10.20452/pamw.15874.

    • Search Google Scholar
    • Export Citation
  • 4.

    Mok Y, Ballew SH, Sang Y, Coresh J, Joshu CE, Platz EA, et al. Albuminuria, kidney function, and cancer risk in the Community. Am J Epidemiol 2020; 189(9): 94250. https://doi.org/10.1093/aje/kwaa043.

    • Search Google Scholar
    • Export Citation
  • 5.

    Kanbay M, Copur S, Yilmaz ZY, Tanriover C, Hasbal NB, Ortiz A, et al. A novel risk factor for malignancy: albuminuria. Eur J Intern Med 2023; 118: 2231. https://doi.org/10.1016/j.ejim.2023.09.010.

    • Search Google Scholar
    • Export Citation
  • 6.

    Ahn SY, Choi YJ, Han K, Ko GJ, Kwon YJ, Park YG. Dipstick proteinuria and cancer incidence: a nationwide population-based study. J Nephrol 2020; 33(5): 106777. https://doi.org/10.1007/s40620-020-00740-1.

    • Search Google Scholar
    • Export Citation
  • 7.

    Mok Y, Matsushita K, Ballew SH, Sang Y, Jung KJ, Lee S, et al. Kidney function, proteinuria, and cancer incidence: the Korean Heart Study. Am J Kidney Dis 2017; 70(4): 51221. https://doi.org/10.1053/j.ajkd.2017.03.018.

    • Search Google Scholar
    • Export Citation
  • 8.

    Tu H, Wen CP, Tsai SP, Chow WH, Wen C, Ye Y, et al. Cancer risk associated with chronic diseases and disease markers: prospective cohort study. BMJ 2018; 360: k134. https://doi.org/10.1136/bmj.k134.

    • Search Google Scholar
    • Export Citation
  • 9.

    Jørgensen L, Heuch I, Jenssen T, Jacobsen BK. Association of albuminuria and cancer incidence. J Am Soc Nephrol 2008; 19(5): 992998. https://doi.org/10.1681/ASN.2007060712.

    • Search Google Scholar
    • Export Citation
  • 10.

    Luo L, Kieneker LM, van der Vegt B, Bakker SJL, Gruppen EG, Casteleijn NF, et al. Urinary albumin excretion and cancer risk: the PREVEND cohort study. Nephrol Dial Transpl 2023; 38(12): 272332. https://doi.org/10.1093/ndt/gfad107.

    • Search Google Scholar
    • Export Citation
  • 11.

    Davey Smith G, Hemani G. Mendelian randomization: genetic anchors for causal inference in epidemiological studies. Hum Mol Genet 2014; 23(R1): R8998. https://doi.org/10.1093/hmg/ddu328.

    • Search Google Scholar
    • Export Citation
  • 12.

    Birney E. Mendelian randomization. Cold Spring Harb Perspect Med 2022; 12(4): a041302. https://doi.org/10.1101/cshperspect.a041302.

  • 13.

    Haas ME, Aragam KG, Emdin CA, Bick AG, International Consortium for Blood Pressure, Hemani G, et al. Genetic association of albuminuria with cardiometabolic disease and blood pressure. Am J Hum Genet 2018; 103(4): 46173. https://doi.org/10.1016/j.ajhg.2018.08.004.

    • Search Google Scholar
    • Export Citation
  • 14.

    Kurki MI, Karjalainen J, Palta P, Sipilä TP, Kristiansson K, Donner KM, et al. FinnGen provides genetic insights from a well-phenotyped isolated population. Nature 2023; 613(7944): 50818. https://doi.org/10.1038/s41586-022-05473-8.

    • Search Google Scholar
    • Export Citation
  • 15.

    Levin MG, Judy R, Gill D, Vujkovic M, Verma SS, Bradford Y, et al. Genetics of height and risk of atrial fibrillation: a Mendelian randomization study. Plos Med 2020; 17(10): e1003288. https://doi.org/10.1371/journal.pmed.1003288.

    • Search Google Scholar
    • Export Citation
  • 16.

    Palmer TM, Lawlor DA, Harbord RM, Sheehan NA, Tobias JH, Timpson NJ, et al. Using multiple genetic variants as instrumental variables for modifiable risk factors. Stat Methods Med Res 2012; 21(3): 22342. https://doi.org/10.1177/0962280210394459.

    • Search Google Scholar
    • Export Citation
  • 17.

    Lawlor DA, Harbord RM, Sterne JA, Timpson N, Davey Smith G. Mendelian randomization: using genes as instruments for making causal inferences in epidemiology. Stat Med 2008; 27(8): 113363. https://doi.org/10.1002/sim.3034.

    • Search Google Scholar
    • Export Citation
  • 18.

    Hemani G, Zheng J, Elsworth B, Wade KH, Haberland V, Baird D, et al. The MR-Base platform supports systematic causal inference across the human phenome. Elife 2018; 7: e34408. https://doi.org/10.7554/eLife.34408.

    • Search Google Scholar
    • Export Citation
  • 19.

    Verbanck M, Chen CY, Neale B, Do R. Detection of widespread horizontal pleiotropy in causal relationships inferred from Mendelian randomization between complex traits and diseases. Nat Genet 2018; 50(5): 6938. https://doi.org/10.1038/s41588-018-0099-7.

    • Search Google Scholar
    • Export Citation
  • 20.

    Reuter S, Gupta SC, Chaturvedi MM, Aggarwal BB. Oxidative stress, inflammation, and cancer: how are they linked? Free Radic Biol Med 2010; 49(11): 160316. https://doi.org/10.1016/j.freeradbiomed.2010.09.006.

    • Search Google Scholar
    • Export Citation
  • 21.

    Storz P. Reactive oxygen species in tumor progression. Front Biosci 2005; 10: 188196. https://doi.org/10.2741/1667.

  • 22.

    Movafagh S, Crook S, Vo K. Regulation of hypoxia-inducible factor-1a by reactive oxygen species: new developments in an old debate. J Cell Biochem 2015; 116(5): 696703. https://doi.org/10.1002/jcb.25074.

    • Search Google Scholar
    • Export Citation
  • 23.

    Qin Z, Li H, Wang L, Geng J, Yang Q, Su B, et al. Systemic immune- inflammation index is associated with increased urinary abumin excretion: a population-based study. Front Immunol 2022; 13: 863640. https://doi.org/10.3389/fimmu.2022.863640.

    • Search Google Scholar
    • Export Citation
  • 24.

    Upadhyay A, Larson MG, Guo CY, Vasan RS, Lipinska I, O'Donnell CJ, et al. Inflammation, kidney function and albuminuria in the Framingham Offspring cohort. Nephrol Dial Transpl 2011; 26(3): 9206. https://doi.org/10.1093/ndt/gfq471.

    • Search Google Scholar
    • Export Citation
  • 25.

    Fernandez-Fernandez B, Izquierdo MC, Valiño-Rivas L, Nastou D, Sanz AB, Ortiz A, et al. Albumin downregulates Klotho in tubular cells. Nephrol Dial Transpl 2018; 33(10): 171222. https://doi.org/10.1093/ndt/gfx376.

    • Search Google Scholar
    • Export Citation
  • 26.

    Kuro-o M. Klotho in health and disease. Curr Opin Nephrol Hypertens 2012; 21(4): 3628. https://doi.org/10.1097/MNH.0b013e32835422ad.

  • 27.

    Mencke R, Olauson H, Hillebrands JL. Effects of Klotho on fibrosis and cancer: a renal focus on mechanisms and therapeutic strategies. Adv Drug Deliv Rev 2017; 121: 85100. https://doi.org/10.1016/j.addr.2017.07.009.

    • Search Google Scholar
    • Export Citation
  • 28.

    Lin Y, Yang Y, Fu T, Lin L, Zhang X, Guo Q, et al. Impairment of kidney function and kidney cancer: a bidirectional Mendelian randomization study. Cancer Med 2023; 12(3): 361022. https://doi.org/10.1002/cam4.5204.

    • Search Google Scholar
    • Export Citation
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Editor-in-Chief

László ROSIVALL (Semmelweis University, Budapest, Hungary)

Managing Editor

Anna BERHIDI (Semmelweis University, Budapest, Hungary)

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  • Ákos KOLLER (Semmelweis University, Budapest, Hungary)
  • Zsolt RADÁK (University of Physical Education, Budapest, Hungary)
  • László LÉNÁRD (University of Pécs, Hungary)
  • Zoltán UNGVÁRI (Semmelweis University, Budapest, Hungary)

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Hungarian Editorial Board

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  • Zoltán BENYÓ (Semmelweis University, Budapest, Hungary)
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  • Magdolna DANK (Semmelweis University, Budapest, Hungary)
  • László DÉTÁRI (Eötvös Loránd University, Budapest, Hungary)
  • Zoltán GIRICZ (Semmelweis University, Budapest, Hungary and Pharmahungary Group, Szeged, Hungary)
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  • Gyula PAPP (University of Szeged, Hungary)
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  • Zoltán SZELÉNYI (University of Pécs, Hungary)
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  • Eric VICAUT (Université de Paris, UMRS 942 INSERM, France)

 

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Physiology International
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