The mendelian randomized study revealed the association of prostatitis with prostate cancer risk.
Mendelian randomization
Prostate cancer
Prostatitis
Journal
Scientific reports
ISSN: 2045-2322
Titre abrégé: Sci Rep
Pays: England
ID NLM: 101563288
Informations de publication
Date de publication:
20 Oct 2024
20 Oct 2024
Historique:
received:
02
05
2024
accepted:
14
10
2024
medline:
21
10
2024
pubmed:
21
10
2024
entrez:
20
10
2024
Statut:
epublish
Résumé
In recent observational studies, a potential link between prostatitis and prostate cancer (PCa) has been hinted at, yet the causality remains ambiguous. In our endeavor to scrutinize the conceivable causal nexus between prostatitis and PCa, we embarked upon a Mendelian randomization (MR) study. MR circumvents arbitrary groupings by employing genetic variations that have a strong association with the exposure as instrumental variables to infer causal relationships between exposures and outcomes. The etiology of PCa remains elusive. Given that prostatitis and prostate cancer occupy the same anatomical region, MR can more effectively delineate their relationship by mitigating confounding variables. This method can indirectly elucidate disease correlations, thereby contributing to cancer prevention strategies. FinnGen Consortium data were used for the prostatitis genome-wide association study (GWAS), including 74,658 participants. UK biobank baseline data (ncase = 3436, ncontrol = 459574), European Bioinformatics Institute Database (ncase = 79148, ncontrol = 61106), and IEU openGWAS database (ncase = 79148, ncontrol = 61106) were used for PCa outcomes, mostly for European population samples. Data from the GWSAs for prostatitis were compared with data from the three GWASs for PCa, respectively, in an analysis of an MR. Utilizing the inverse variance weighting (IVW) methodology as our primary analytical framework, we delved into a meticulous exploration of the conceivable causal association between prostatitis and PCa. Furthermore, we deployed supplementary methodologies, including Maximum Likelihood, MR-Egger, weighted median, and MR-PRESSO, to thoroughly assess and scrutinize the causality aspect comprehensively. Cochran's Q statistic is employed as a metric to quantify the heterogeneity inherent in instrumental variables. The inverse variance weighted analysis revealed no discernible effect of prostatitis on PCa in the three PCa GWAS databases (odds ratio [OR]: 1.001, 95% Confidence Interval [CI]: 0.999-1.002, p = 0.28), (OR: 1.015, 95% CI: 0.981-1.050, p = 0.40), (OR: 1.015, 95% CI: 0.981-1.050, p = 0.40). Similarly, employing MR-Egger did not yield substantial evidence (OR: 0.999, 95% CI: 0.999-1.002, p = 0.89), (OR: 1.103, 95% CI: 1.006-1.209, p = 0.07), (OR: 1.103, 95% CI: 1.006-1.209, p = 0.07). The weighted median analysis also failed to provide convincing support for the impact of prostatitis on the incidence of PCa (OR: 1.001, 95% CI: 1.000-1.002, p = 0.064), (OR: 0.989, 95% CI: 0.946-1.034, p = 0.64), (OR: 0.989, 95% CI: 0.945-1.036, p = 0.65). The results of the MR showed no causality from prostatitis to PCa.
Identifiants
pubmed: 39428439
doi: 10.1038/s41598-024-76355-4
pii: 10.1038/s41598-024-76355-4
doi:
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
24643Subventions
Organisme : Health and Technology Project of Hangzhou
ID : A20210162
Organisme : Zhejiang Medical Science and Technology Project
ID : 2024KY230
Organisme : Zhejiang Medical Science and Technology Project
ID : 2022507093
Organisme : Hangzhou Health and Technology Project
ID : ZD20210043
Informations de copyright
© 2024. The Author(s).
Références
Siegel, R. L., Miller, K. D., Wagle, N. S. & Jemal, A. Cancer statistics, 2023. CA Cancer J. Clin. 73 (1), 17–48. https://doi.org/10.3322/caac.21763 (2023).
doi: 10.3322/caac.21763
pubmed: 36633525
Cheng, Q. et al. Pre-existing castration-resistant prostate cancer-like cells in primary prostate cancer promote resistance to hormonal therapy. Eur. Urol. 81 (5), 446–455. https://doi.org/10.1016/j.eururo.2021.12.039 (2022).
doi: 10.1016/j.eururo.2021.12.039
pubmed: 35058087
pmcid: 9018600
Kodama, H. et al. Castration-resistant prostate cancer without metastasis at presentation may achieve cancer-specific survival in patients who underwent prior radical prostatectomy. Int. Urol. Nephrol. 52 (4), 671–679. https://doi.org/10.1007/s11255-019-02339-3 (2020).
doi: 10.1007/s11255-019-02339-3
pubmed: 31897875
Bergengren, O. et al. 2022 update on prostate cancer epidemiology and risk factors—a systematic review. Eur. Urol. 84 (2), 191–206. https://doi.org/10.1016/j.eururo.2023.04.021 (2023).
doi: 10.1016/j.eururo.2023.04.021
pubmed: 37202314
pmcid: 10851915
Krieger, J. N. et al. Epidemiology of prostatitis. Int. J. Antimicrob. Agents. 31 (Suppl 1), S85–90. https://doi.org/10.1016/j.ijantimicag.2007.08.028 (2008).
doi: 10.1016/j.ijantimicag.2007.08.028
pubmed: 18164907
Oseni, S. O. et al. The molecular basis and clinical consequences of chronic inflammation in prostatic diseases: prostatitis, benign prostatic hyperplasia, and prostate cancer. Cancers (Basel). 15 (12), 3110. https://doi.org/10.3390/cancers15123110 (2023).
doi: 10.3390/cancers15123110
pubmed: 37370720
De Matteis, R. et al. Aspirin activates resolution pathways to reprogram T cell and macrophage responses in colitis-associated colorectal cancer. Sci. Adv. 8 (5), eabl5420. https://doi.org/10.1126/sciadv.abl5420 (2022).
doi: 10.1126/sciadv.abl5420
pubmed: 35108049
pmcid: 8809687
Barton, M. K. Daily aspirin may reduce mortality from prostate cancer with risk of high recurrence. CA Cancer J. Clin. 65 (2), 83–84. https://doi.org/10.3322/caac.21263 (2015).
doi: 10.3322/caac.21263
pubmed: 25640813
Rybicki, B. et al. Racial differences in the relationship between clinical prostatitis, presence of inflammation in benign prostate and subsequent risk of prostate cancer. Prostate Cancer Prostatic Dis. 19 (2), 145–150. https://doi.org/10.1038/pcan.2015.54 (2016).
doi: 10.1038/pcan.2015.54
pubmed: 26620738
Mantovani, A., Allavena, P., Sica, A. & Balkwill, F. Cancer-related inflammation. Nature. 454 (7203), 436–444. https://doi.org/10.1038/nature07205 (2008).
doi: 10.1038/nature07205
pubmed: 18650914
Coussens, L. M. & Werb, Z. Inflammation and cancer. Nature. 420 (6917), 860–867. https://doi.org/10.1038/nature01322 (2002).
doi: 10.1038/nature01322
pubmed: 12490959
pmcid: 2803035
Locati, M., Curtale, G., Mantovani, A. & Diversity mechanisms and significance of macrophage plasticity. Annu. Rev. Pathol. 15, 123–147. https://doi.org/10.1146/annurev-pathmechdis-012418-012718 (2020).
doi: 10.1146/annurev-pathmechdis-012418-012718
pubmed: 31530089
Zhong, W. et al. Gut dysbiosis promotes prostate cancer progression and docetaxel resistance via activating NF-κB-IL6-STAT3 axis. Microbiome. 10 (1), 94. https://doi.org/10.1186/s40168-022-01289-w (2022).
doi: 10.1186/s40168-022-01289-w
pubmed: 35710492
pmcid: 9202177
Elinav, E. et al. Inflammation-induced cancer: crosstalk between tumours, immune cells and microorganisms. Nat. Rev. Cancer. 13 (11), 759–771. https://doi.org/10.1038/nrc3611 (2013).
doi: 10.1038/nrc3611
pubmed: 24154716
Thomas-Jardin, S. E., Dahl, H., Nawas, A. F., Bautista, M. & Delk, N. A. NF-κB signaling promotes castration-resistant prostate cancer initiation and progression. Pharmacol. Ther. 211, 107538. https://doi.org/10.1016/j.pharmthera.2020.107538 (2020).
doi: 10.1016/j.pharmthera.2020.107538
pubmed: 32201312
Mountjoy, E. et al. An open approach to systematically prioritize causal variants and genes at all published human GWAS trait-associated loci. Nat. Genet. 53 (11), 1527–1533. https://doi.org/10.1038/s41588-021-00945-5 (2021).
doi: 10.1038/s41588-021-00945-5
pubmed: 34711957
pmcid: 7611956
Kurki, M. I. et al. FinnGen provides genetic insights from a well-phenotyped isolated population. Nature. 613 (7944), 508–518. https://doi.org/10.1038/s41586-022-05473-8 (2023).
doi: 10.1038/s41586-022-05473-8
pubmed: 36653562
pmcid: 9849126
Vaucher, J. et al. Cannabis use and risk of schizophrenia: a mendelian randomization study. Mol. Psychiatry. 23 (5), 1287–1292. https://doi.org/10.1038/mp.2016.252 (2018).
doi: 10.1038/mp.2016.252
pubmed: 28115737
Pierce, B. L., Ahsan, H. & VanderWeele, T. J. Power and instrument strength requirements for mendelian randomization studies using multiple genetic variants. Int. J. Epidemiol. 40 (3), 740–752. https://doi.org/10.1093/ije/dyq151 (2011).
doi: 10.1093/ije/dyq151
pubmed: 20813862
Bowden, J., Davey Smith, G. & Burgess, S. Mendelian randomization with invalid instruments: effect estimation and bias detection through Egger regression. Int. J. Epidemiol. 44 (2), 512–525. https://doi.org/10.1093/ije/dyv080 (2015).
doi: 10.1093/ije/dyv080
pubmed: 26050253
pmcid: 4469799
Staiger, D. & Stock, J. H. Instrumental variables regression with weak instruments. Econometrica. 65 (3), 557–586. https://doi.org/10.2307/2171753 (1997).
doi: 10.2307/2171753
Bycroft, C. et al. The UK Biobank resource with deep phenotyping and genomic data. Nature. 562 (7726), 203–209. https://doi.org/10.1038/s41586-018-0579-z (2018).
doi: 10.1038/s41586-018-0579-z
pubmed: 30305743
pmcid: 6786975
Cantelli, G. et al. The European Bioinformatics Institute (EMBL-EBI) in 2021. Nucleic Acids Res. 50 (D1), D11–D19. https://doi.org/10.1093/nar/gkab1127 (2022).
doi: 10.1093/nar/gkab1127
pubmed: 34850134
Long, Y., Tang, L., Zhou, Y., Zhao, S. & Zhu, H. Causal relationship between gut microbiota and cancers: a two-sample mendelian randomisation study. BMC Med. 21 (1), 66. https://doi.org/10.1186/s12916-023-02761-6 (2023).
doi: 10.1186/s12916-023-02761-6
pubmed: 36810112
pmcid: 9945666
Burgess, S., Dudbridge, F. & Thompson, S. G. Combining information on multiple instrumental variables in mendelian randomization: comparison of allele score and summarized data methods. Stat. Med. 35 (11), 1880–1906. https://doi.org/10.1002/sim.6835 (2016).
doi: 10.1002/sim.6835
pubmed: 26661904
Bowden, J. & Holmes, M. V. Meta-analysis and mendelian randomization: a review. Res. Synth. Methods. 10 (4), 486–496. https://doi.org/10.1002/jrsm.1346 (2019).
doi: 10.1002/jrsm.1346
pubmed: 30861319
pmcid: 6973275
Burgess, S. & Thompson, S. G. Interpreting findings from mendelian randomization using the MR-Egger method. Eur. J. Epidemiol. 32 (5), 377–389. https://doi.org/10.1007/s10654-017-0255-x (2017).
doi: 10.1007/s10654-017-0255-x
pubmed: 28527048
pmcid: 5506233
Wang, M. et al. Coffee consumption and prostate cancer risk: results from National Health and Nutrition Examination Survey 1999–2010 and mendelian randomization analyses. Nutrients. 13 (7), 2317. https://doi.org/10.3390/nu13072317 (2021).
doi: 10.3390/nu13072317
pubmed: 34371827
pmcid: 8308488
Sekula, P., Del Greco, M. F., Pattaro, C. & Köttgen, A. Mendelian randomization as an approach to assess causality using observational data. J. Am. Soc. Nephrol. 27 (11), 3253–3265. https://doi.org/10.1681/ASN.2016010098 (2016).
doi: 10.1681/ASN.2016010098
pubmed: 27486138
pmcid: 5084898
Dikov, D., Bachurska, S., Staikov, D. & Sarafian, V. Intraepithelial lymphocytes in relation to NIH category IV prostatitis in autopsy prostate. Prostate. 75 (10), 1074–1084. https://doi.org/10.1002/pros.22991 (2015).
doi: 10.1002/pros.22991
pubmed: 25917232
A Prospective Study of Chronic Inflammation in Benign Prostate Tissue and Risk of Prostate Cancer: Linked PCPT and SELECT Cohorts - PMC. Accessed December 18. (2023). https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5626618/
Fantel, A. G., Mackler, B., Stamps, L. D., Tran, T. T. & Person, R. E. Reactive oxygen species and DNA oxidation in fetal rat tissues. Free Radic. Biol. Med. 25 (1), 95–103. https://doi.org/10.1016/s0891-5849(98)00042-2 (1998).
doi: 10.1016/s0891-5849(98)00042-2
pubmed: 9655527
Zhang, Y. et al. Reactive oxygen species (ROS)-degradable polymeric nanoplatform for hypoxia-targeted gene delivery: unpacking DNA and reducing toxicity. Biomacromolecules. 20 (5), 1899–1913. https://doi.org/10.1021/acs.biomac.9b00054 (2019).
doi: 10.1021/acs.biomac.9b00054
pubmed: 30922055
Reuter, S., Gupta, S. C., Chaturvedi, M. M. & Aggarwal, B. B. Oxidative stress, inflammation, and cancer: how are they linked? Free Radic. Biol. Med. 49 (11), 1603–1616. https://doi.org/10.1016/j.freeradbiomed.2010.09.006 (2010).
doi: 10.1016/j.freeradbiomed.2010.09.006
pubmed: 20840865
pmcid: 2990475
Shahed, A. R. & Shoskes, D. A. Oxidative stress in prostatic fluid of patients with chronic pelvic pain syndrome: correlation with gram positive bacterial growth and treatment response. J. Androl. 21 (5), 669–675 (2000).
doi: 10.1002/j.1939-4640.2000.tb02135.x
pubmed: 10975414
Cheng, I. et al. Prostatitis, sexually transmitted diseases, and prostate cancer: the California men’s Health Study. PLoS One. 5 (1), e8736. https://doi.org/10.1371/journal.pone.0008736 (2010).
doi: 10.1371/journal.pone.0008736
pubmed: 20090948
pmcid: 2806913
Roberts, R. O., Bergstralh, E. J., Bass, S. E., Lieber, M. M. & Jacobsen, S. J. Prostatitis as a risk factor for prostate cancer. Epidemiology. 15 (1), 93–99. https://doi.org/10.1097/01.ede.0000101022.38330.7c (2004).
doi: 10.1097/01.ede.0000101022.38330.7c
pubmed: 14712152
Nelson, W. G., De Marzo, A. M. & Isaacs, W. B. Prostate cancer. N Engl. J. Med. 349 (4), 366–381. https://doi.org/10.1056/NEJMra021562 (2003).
doi: 10.1056/NEJMra021562
pubmed: 12878745
Putzi, M. J. & De Marzo, A. M. Morphologic transitions between proliferative inflammatory atrophy and high-grade prostatic intraepithelial neoplasia. Urology. 56 (5), 828–832. https://doi.org/10.1016/s0090-4295(00)00776-7 (2000).
doi: 10.1016/s0090-4295(00)00776-7
pubmed: 11068311
Staal, J. & Beyaert, R. Inflammation and NF-κB signaling in prostate cancer: mechanisms and clinical implications. Cells. 7 (9), 122. https://doi.org/10.3390/cells7090122 (2018).
doi: 10.3390/cells7090122
pubmed: 30158439
pmcid: 6162478
Poma, P. NF-κB and disease. Int. J. Mol. Sci. 21 (23), 9181. https://doi.org/10.3390/ijms21239181 (2020).
doi: 10.3390/ijms21239181
pubmed: 33276434
pmcid: 7730361
Lyu, Q. et al. Hsp70 and NF-kB mediated control of innate inflammatory responses in a canine macrophage cell line. Int. J. Mol. Sci. 21 (18), 6464. https://doi.org/10.3390/ijms21186464 (2020).
doi: 10.3390/ijms21186464
pubmed: 32899721
pmcid: 7555705
Bonollo, F., Thalmann, G. N., Kruithof-de Julio, M. & Karkampouna, S. The role of cancer-associated fibroblasts in prostate cancer tumorigenesis. Cancers (Basel). 12 (7), 1887. https://doi.org/10.3390/cancers12071887 (2020).
doi: 10.3390/cancers12071887
pubmed: 32668821
Chiarugi, P., Paoli, P. & Cirri, P. Tumor microenvironment and metabolism in prostate cancer. Semin Oncol. 41 (2), 267–280. https://doi.org/10.1053/j.seminoncol.2014.03.004 (2014).
doi: 10.1053/j.seminoncol.2014.03.004
pubmed: 24787298
Gabbiani, G. The myofibroblast in wound healing and fibrocontractive diseases. J. Pathol. 200 (4), 500–503. https://doi.org/10.1002/path.1427 (2003).
doi: 10.1002/path.1427
pubmed: 12845617
Levesque, C. & Nelson, P. S. Cellular constituents of the prostate stroma: key contributors to prostate cancer progression and therapy resistance. Cold Spring Harb Perspect. Med. 8 (8), a030510. https://doi.org/10.1101/cshperspect.a030510 (2018).
doi: 10.1101/cshperspect.a030510
pubmed: 28490538
pmcid: 5681439
Schneider, L. et al. Post-prostatic-massage urine exosomes of men with chronic prostatitis/chronic pelvic pain syndrome carry prostate-cancer-typical microRNAs and activate proto-oncogenes. Mol. Oncol. 17 (3), 445–468. https://doi.org/10.1002/1878-0261.13329 (2023).
doi: 10.1002/1878-0261.13329
pubmed: 36321189
Vasavada, S. R., Dobbs, R. W., Kajdacsy -Balla André, A., Abern, M. R. & Moreira, D. M. Inflammation on prostate needle biopsy is associated with lower prostate cancer risk: a meta-analysis. J. Urol. 199 (5), 1174–1181. https://doi.org/10.1016/j.juro.2017.11.120 (2018).
doi: 10.1016/j.juro.2017.11.120
pubmed: 29246732
Moreira, D. M. et al. Baseline prostate inflammation is associated with a reduced risk of prostate cancer in men undergoing repeat prostate biopsy: results from the REDUCE study. Cancer. 120 (2), 190–196. https://doi.org/10.1002/cncr.28349 (2014).
doi: 10.1002/cncr.28349
pubmed: 24323568
Moreira, D. M. et al. The combination of histological prostate atrophy and inflammation is associated with lower risk of prostate cancer in biopsy specimens. Prostate Cancer Prostatic Dis. 20 (4), 413–417. https://doi.org/10.1038/pcan.2017.30 (2017).
doi: 10.1038/pcan.2017.30
pubmed: 28585572
Quail, D. F. & Joyce, J. A. Molecular pathways: deciphering mechanisms of resistance to macrophage-targeted therapies. Clin. Cancer Res. 23 (4), 876–884. https://doi.org/10.1158/1078-0432.CCR-16-0133 (2017).
doi: 10.1158/1078-0432.CCR-16-0133
pubmed: 27895033
Saccani, A. et al. p50 nuclear factor-kappab overexpression in tumor-associated macrophages inhibits M1 inflammatory responses and antitumor resistance. Cancer Res. 66 (23), 11432–11440. https://doi.org/10.1158/0008-5472.CAN-06-1867 (2006).
doi: 10.1158/0008-5472.CAN-06-1867
pubmed: 17145890
Hagemann, T. et al. Re-educating tumor-associated macrophages by targeting NF-kappaB. J. Exp. Med. 205 (6), 1261–1268. https://doi.org/10.1084/jem.20080108 (2008).
doi: 10.1084/jem.20080108
pubmed: 18490490
pmcid: 2413024
Dajee, M. et al. NF-kappaB blockade and oncogenic ras trigger invasive human epidermal neoplasia. Nature. 421 (6923), 639–643. https://doi.org/10.1038/nature01283 (2003).
doi: 10.1038/nature01283
pubmed: 12571598
Carter, A. R. et al. Mendelian randomisation for mediation analysis: current methods and challenges for implementation. Eur. J. Epidemiol. 36 (5), 465–478. https://doi.org/10.1007/s10654-021-00757-1 (2021).
doi: 10.1007/s10654-021-00757-1
pubmed: 33961203
pmcid: 8159796
Sfanos, K. S., Isaacs, W. B. & Marzo, A. M. D. Infections and inflammation in prostate cancer. Am. J. Clin. Exp. Urol. 1 (1), 3–11 (2013).
pubmed: 25110720
pmcid: 4219279
Sfanos, K. S., Yegnasubramanian, S., Nelson, W. G. & De Marzo, A. M. The inflammatory microenvironment and microbiome in prostate cancer development. Nat. Rev. Urol. 15 (1), 11–24. https://doi.org/10.1038/nrurol.2017.167 (2018).
doi: 10.1038/nrurol.2017.167
pubmed: 29089606
Burger, M. et al. Epidemiology and risk factors of urothelial bladder cancer. Eur. Urol. 63 (2), 234–241. https://doi.org/10.1016/j.eururo.2012.07.033 (2013).
doi: 10.1016/j.eururo.2012.07.033
pubmed: 22877502
Vitale, I., Manic, G., Coussens, L. M., Kroemer, G. & Galluzzi, L. Macrophages and metabolism in the tumor microenvironment. Cell. Metab. 30 (1), 36–50. https://doi.org/10.1016/j.cmet.2019.06.001 (2019).
doi: 10.1016/j.cmet.2019.06.001
pubmed: 31269428
Bouras, E. et al. Circulating inflammatory cytokines and risk of five cancers: a mendelian randomization analysis. BMC Med. 20 (1), 3. https://doi.org/10.1186/s12916-021-02193-0 (2022).
doi: 10.1186/s12916-021-02193-0
pubmed: 35012533
pmcid: 8750876