Association between Parkinson's disease and risk of colorectal cancer: A systematic review and meta-analysis

Abstract

This study aims to investigate the relationship between Parkinson's disease (PD) and colorectal cancer (CRC) risk by a systematic review and meta-analysis. Using Embase, Pubmed, and Cochrane Library databases, 21 articles reporting clinical data of 1,635,873 PD patients and 10,388,842 healthy individuals were finally included. Based on the results of pooled analysis, we found that PD patients exhibited a decreased risk of CRC (relative risk (RR) = 0.74; 95% confidence interval (CI), 0.68–0.80). In contrast to case-control (RR = 0.80; 95% CI, 0.64–1) and cohort studies (RR = 0.72; 95% CI, 0.66–0.79), the combined risk of PD patients with CRC in Asian nations (RR = 0.67; 95% CI, 0.58–0.78) was lower than that in Western countries (RR = 0.76; 95% CI, 0.70–0.82). In comparison to rectal cancer (RR = 0.82; 95% CI, 0.69–0.97), PD patients exhibited a lower combined risk of colon cancer (RR = 0.76; 95% CI, 0.67–0.86). Furthermore, the combined CRC risks for patients in studies published before 2010 and after 2010 were 0.76 (RR = 0.76; 95% CI, 0.66–0.88) and 0.74 (RR = 0.74; 95% CI, 0.68–0.80), respectively. These findings indicate that patients with PD had a reduced risk of CRC. Future studies are merited in exploring pathological molecular linkages or underlying mechanisms of inverse association between CRC and PD.

Keywords

colorectal cancer / meta-analysis / Parkinson's disease / pooled analysis / systematic review

References

[1] Bloem BR, Okun MS, Klein C. Parkinson's disease. Lancet. 2021; 397(10291): 2284-2303.

[2] Dorsey ER, Elbaz A, Nichols E, et al. Global, regional, and national burden of Parkinson's disease, 1990–2016: a systematic analysis for the Global Burden of Disease Study 2016. Lancet Neurol. 2018; 17(11): 939-953.

[3] Qi S, Yin P, Wang L, et al. Prevalence of Parkinson's disease: a community-based study in China. Mov Disorders. 2021; 36(12): 2940-2944.

[4] Jankovic J. Parkinson's disease: clinical features and diagnosis. J Neurol Neurosurg Psychiatry. 2008; 79(4): 368-376.

[5] Ong EL, Goldacre R, Goldacre M. Differential risks of cancer types in people with Parkinson's disease: a national record-linkage study. Eur J Cancer. 2014; 50(14): 2456-2462.

[6] Hang Z, Lei T, Zeng Z, Cai S, Bi W, Du H. Composition of intestinal flora affects the risk relationship between Alzheimer's disease/Parkinson's disease and cancer. Biomed Pharmacother = Biomed Pharmacother. 2022; 145:112343.

[7] Leong YQ, Lee SWH, Ng KY. Cancer risk in Parkinson disease: an updated systematic review and meta-analysis. Eur J Neurol. 2021; 28(12): 4219-4237.

[8] Lin PY, Chang SN, Hsiao TH, Huang BT, Lin CH, Yang PC. Association between Parkinson disease and risk of cancer in Taiwan. JAMA Oncol. 2015; 1(5): 633-640.

[9] Kim SY, Choi HG, Kim YH, et al. Longitudinal study of the inverse relationship between Parkinson's disease and cancer in Korea. npj Parkinson's Dis. 2023; 9(1): 116.

[10] Morgan E, Arnold M, Gini A, et al. Global burden of colorectal cancer in 2020 and 2040: incidence and mortality estimates from GLOBOCAN. Gut. 2023; 72(2): 338-344.

[11] Park JH, Kim DH, Park YG, et al. Cancer risk in patients with Parkinson's disease in South Korea: a nationwide, population-based cohort study. Eur J Cancer. 2019; 117: 5-13.

[12] Lu L, Dai M, Mullins CS, Schafmayer C, Linnebacher M. Global association of cause-specific mortality between the major gastrointestinal cancers and Parkinson's disease for the first two decades of the new millennium. Aging Dis. 2022; 13(2): 534-539.

[13] Powers KM, Smith-Weller T, Franklin GM, Longstreth Jr. WT, Swanson PD, Checkoway H. Diabetes, smoking, and other medical conditions in relation to Parkinson's disease risk. Parkinsonism Rel Disord. 2006; 12(3): 185-189.

[14] Page MJ, McKenzie JE, Bossuyt PM, et al. The PRISMA 2020 statement: an updated guideline for reporting systematic reviews. BMJ. 2021; 372:n71.

[15] Stang A. Critical evaluation of the Newcastle-Ottawa scale for the assessment of the quality of nonrandomized studies in meta-analyses. Eur J Epidemiol. 2010; 25(9): 603-605.

[16] Becker C, Brobert GP, Johansson S, Jick SS, Meier CR. Cancer risk in association with Parkinson disease: a population-based study. Parkinsonism Rel Disord. 2010; 16(3): 186-190.

[17] Boursi B, Mamtani R, Haynes K, Yang YX. Parkinson's disease and colorectal cancer risk-a nested case control study. Cancer Epidemiol. 2016; 43: 9-14.

[18] Freedman DM, Wu J, Chen H, et al. Associations between cancer and Parkinson's disease in U.S. elderly adults. Int J Epidemiol. 2016; 45(3): 741-751.

[19] Fois AF, Wotton CJ, Yeates D, Turner MR, Goldacre MJ. Cancer in patients with motor neuron disease, multiple sclerosis and Parkinson's disease: record linkage studies. J Neurol Neurosurg Psychiatry. 2010; 81(2): 215-221.

[20] Guttman M, Slaughter PM, Theriault ME, DeBoer DP, Naylor CD. Parkinsonism in Ontario: comorbidity associated with hospitalization in a large cohort. Mov Disorders. 2004; 19(1): 49-53.

[21] Driver JA, Logroscino G, Buring JE, Gaziano JM, Kurth T. A prospective cohort study of cancer incidence following the diagnosis of Parkinson's disease. Cancer Epidemiol Biomarkers Prevent: Publ Am Assoc Cancer Res Cosponsored Am Soc Prevent Oncol. 2007; 16(6): 1260-1265.

[22] Wirdefeldt K, Weibull CE, Chen H, et al. Parkinson's disease and cancer: a register-based family study. Am J Epidemiol. 2014; 179(1): 85-94.

[23] Lo RY, Tanner CM, Van Den Eeden SK, Albers KB, Leimpeter AD, Nelson LM. Comorbid cancer in Parkinson's disease. Mov Disorders. 2010; 25(12): 1809-1817.

[24] Rugbjerg K, Friis S, Lassen CF, Ritz B, Olsen JH. Malignant melanoma, breast cancer and other cancers in patients with Parkinson's disease. Int J Cancer. 2012; 131(8): 1904-1911.

[25] Olsen JH, Friis S, Frederiksen K, McLaughlin JK, Mellemkjaer L, Møller H. Atypical cancer pattern in patients with Parkinson's disease. Br J Cancer. 2005; 92(1): 201-205.

[26] Peretz C, Gurel R, Rozani V, et al. Cancer incidence among Parkinson's disease patients in a 10-yrs time-window around disease onset: a large-scale cohort study. Parkinsonism Rel Disord. 2016; 28: 68-72.

[27] Kareus SA, Figueroa KP, Cannon-Albright LA, Pulst SM. Shared predispositions of parkinsonism and cancer: a population-based pedigree-linked study. Arch Neurol. 2012; 69(12): 1572-1577.

[28] Sun LM, Liang JA, Chang SN, Sung FC, Muo CH, Kao CH. Analysis of Parkinson's disease and subsequent cancer risk in Taiwan: a nationwide population-based cohort study. Neuroepidemiology. 2011; 37(2): 114-119.

[29] Freedman DM, Pfeiffer RM. Associations between Parkinson disease and cancer in US Asian Americans. JAMA oncol. 2016; 2(8): 1093-1094.

[30] Agalliu I, Ortega RA, Luciano MS, et al. Cancer outcomes among Parkinson's disease patients with leucine rich repeat kinase 2 mutations, idiopathic Parkinson's disease patients, and nonaffected controls. Mov Disorders. 2019; 34(9): 1392-1398.

[31] Lee JYS, Ng JH, Saffari SE, Tan EK. Parkinson's disease and cancer: a systematic review and meta-analysis on the influence of lifestyle habits, genetic variants, and gender. Aging. 2022; 14(5): 2148-2173.

[32] Ejma M, Madetko N, Brzecka A, et al. The links between Parkinson's disease and cancer. Biomedicines. 2020; 8(10):416.

[33] Wang X, Wang ZB, Luo C, et al. The prospective value of dopamine receptors on bio-behavior of tumor. J Cancer. 2019; 10(7): 1622-1632.

[34] Garber K. Parkinson's disease and cancer: the unexplored connection. J Natl Cancer Inst. 2010; 102(6): 371-374.

[35] Chen Q, Zhong L, Zhou C, et al. Knockdown of Parkinson's disease-related gene ATP13A2 reduces tumorigenesis via blocking autophagic flux in colon cancer. Cell Biosci. 2020; 10(1): 144.

[36] Keshavarzian A, Green SJ, Engen PA, et al. Colonic bacterial composition in Parkinson's disease. Mov Disorders. 2015; 30(10): 1351-1360.

[37] Tsao SP, Nurrahma BA, Kumar R, et al. Probiotic enhancement of antioxidant capacity and alterations of gut microbiota composition in 6-hydroxydopamin-induced Parkinson's disease rats. Antioxidants. 2021; 10(11):1823.

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2025 The Author(s). Ibrain published by Affiliated Hospital of Zunyi Medical University (AHZMU) and Wiley-VCH GmbH.