Patients with periodontitis might increase the risk of urologic cancers: a bidirectional two-sample Mendelian randomization study

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Abstract

Background

Numerous observational epidemiological studies have reported a bidirectional relationship between periodontitis and urological cancers. However, the causal link between these two phenotypes remains uncertain. This study aimed to examine the bidirectional causal association between periodontitis and four types of urological tumors, specifically kidney cancer (KC), prostate cancer (PC), bladder cancer (BC), and testis cancer (TC).

Methods

Based on large-scale genome-wide association study (GWAS) data, we utilized the two-sample Mendelian randomization (MR) approach to evaluate causal relationships between periodontitis and urological cancers. Several MR methods covering various consistency assumptions were applied in this study, including contamination mixture and Robust Adjusted Profile Score to obtain robust results. Summary-level data of individuals with European ancestry were extracted from the UK Biobank, the Kaiser GERA cohorts, and the FinnGen consortium.

Results

Our findings revealed significant positive genetic correlations between periodontitis and kidney cancer (OR 1.287; 95% CI 1.04, 1.594; P = 0.020). We did not find a significant association of periodontitis on prostate cancer, bladder cancer, and testis cancer. In reverse MR, no significant results were observed supporting the effect of urologic cancers on periodontitis (all P > 0.05).

Conclusion

Our study provides the evidence of a potential causal relationship between periodontitis and kidney cancer. However, large-scale studies are warranted to confirm and elucidate the underlying mechanisms of this association.

Supplementary Information

The online version contains supplementary material available at 10.1007/s11255-023-03858-w.

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Most cited references 50

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Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries

Hyuna Sung, Jacques Ferlay, Rebecca Siegel … (2021)

This article provides an update on the global cancer burden using the GLOBOCAN 2020 estimates of cancer incidence and mortality produced by the International Agency for Research on Cancer. Worldwide, an estimated 19.3 million new cancer cases (18.1 million excluding nonmelanoma skin cancer) and almost 10.0 million cancer deaths (9.9 million excluding nonmelanoma skin cancer) occurred in 2020. Female breast cancer has surpassed lung cancer as the most commonly diagnosed cancer, with an estimated 2.3 million new cases (11.7%), followed by lung (11.4%), colorectal (10.0 %), prostate (7.3%), and stomach (5.6%) cancers. Lung cancer remained the leading cause of cancer death, with an estimated 1.8 million deaths (18%), followed by colorectal (9.4%), liver (8.3%), stomach (7.7%), and female breast (6.9%) cancers. Overall incidence was from 2-fold to 3-fold higher in transitioned versus transitioning countries for both sexes, whereas mortality varied <2-fold for men and little for women. Death rates for female breast and cervical cancers, however, were considerably higher in transitioning versus transitioned countries (15.0 vs 12.8 per 100,000 and 12.4 vs 5.2 per 100,000, respectively). The global cancer burden is expected to be 28.4 million cases in 2040, a 47% rise from 2020, with a larger increase in transitioning (64% to 95%) versus transitioned (32% to 56%) countries due to demographic changes, although this may be further exacerbated by increasing risk factors associated with globalization and a growing economy. Efforts to build a sustainable infrastructure for the dissemination of cancer prevention measures and provision of cancer care in transitioning countries is critical for global cancer control.

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Cancer statistics, 2022

Rebecca Siegel, Kimberly D Miller, Hannah Fuchs … (2022)

Each year, the American Cancer Society estimates the numbers of new cancer cases and deaths in the United States and compiles the most recent data on population-based cancer occurrence and outcomes. Incidence data (through 2018) were collected by the Surveillance, Epidemiology, and End Results program; the National Program of Cancer Registries; and the North American Association of Central Cancer Registries. Mortality data (through 2019) were collected by the National Center for Health Statistics. In 2022, 1,918,030 new cancer cases and 609,360 cancer deaths are projected to occur in the United States, including approximately 350 deaths per day from lung cancer, the leading cause of cancer death. Incidence during 2014 through 2018 continued a slow increase for female breast cancer (by 0.5% annually) and remained stable for prostate cancer, despite a 4% to 6% annual increase for advanced disease since 2011. Consequently, the proportion of prostate cancer diagnosed at a distant stage increased from 3.9% to 8.2% over the past decade. In contrast, lung cancer incidence continued to decline steeply for advanced disease while rates for localized-stage increased suddenly by 4.5% annually, contributing to gains both in the proportion of localized-stage diagnoses (from 17% in 2004 to 28% in 2018) and 3-year relative survival (from 21% to 31%). Mortality patterns reflect incidence trends, with declines accelerating for lung cancer, slowing for breast cancer, and stabilizing for prostate cancer. In summary, progress has stagnated for breast and prostate cancers but strengthened for lung cancer, coinciding with changes in medical practice related to cancer screening and/or treatment. More targeted cancer control interventions and investment in improved early detection and treatment would facilitate reductions in cancer mortality.

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METAL: fast and efficient meta-analysis of genomewide association scans

Cristen Willer, Yun Li, Gonçalo R Abecasis (2010)

Summary: METAL provides a computationally efficient tool for meta-analysis of genome-wide association scans, which is a commonly used approach for improving power complex traits gene mapping studies. METAL provides a rich scripting interface and implements efficient memory management to allow analyses of very large data sets and to support a variety of input file formats. Availability and implementation: METAL, including source code, documentation, examples, and executables, is available at http://www.sph.umich.edu/csg/abecasis/metal/ Contact: goncalo@umich.edu

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Author and article information

Contributors

Banghua Liao: 11511761@qq.com

Ga Liao: liaoga@hotmail.com

Jin Huang:

ORCID: http://orcid.org/0000-0001-7160-2314

michael_huangjin@163.com

Journal

Journal ID (nlm-ta): Int Urol Nephrol

Journal ID (iso-abbrev): Int Urol Nephrol

Title: International Urology and Nephrology

Publisher: Springer Netherlands (Dordrecht )

ISSN (Print): 0301-1623

ISSN (Electronic): 1573-2584

Publication date (Electronic): 28 November 2023

Publication date PMC-release: 28 November 2023

Publication date (Print): 2024

Volume: 56

Issue: 4

Pages: 1243-1251

Affiliations

[1 ]GRID grid.412901.f, ISNI 0000 0004 1770 1022, Health Management Center, General Practice Medical Center, Medical Device Regulatory Research and Evaluation Center, , West China Hospital, Sichuan University, ; Chengdu, Sichuan People’s Republic of China

[2 ]GRID grid.412901.f, ISNI 0000 0004 1770 1022, West China School of Public Health, , West China Hospital, Sichuan University, ; Chengdu, Sichuan People’s Republic of China

[3 ]Engineering Research Center of Medical Information Technology, Ministry of Education, West China Hospital of Sichuan University, ( https://ror.org/007mrxy13) Chengdu, Sichuan People’s Republic of China

[4 ]GRID grid.412901.f, ISNI 0000 0004 1770 1022, Department of Urology, Institute of Urology (Laboratory of Reconstructive Urology), , West China Hospital, Sichuan University, ; Chengdu, Sichuan 610044 People’s Republic of China

[5 ]GRID grid.13291.38, ISNI 0000 0001 0807 1581, State Key Laboratory of Oral Diseases, , National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan University, ; Chengdu, Sichuan 610041 People’s Republic of China

Author information

Jin Huang http://orcid.org/0000-0001-7160-2314

Article

Publisher ID: 3858

DOI: 10.1007/s11255-023-03858-w

PMC ID: 10923993

PubMed ID: 38015384

SO-VID: 7ea1a030-6694-4ae6-88ba-ee08a5c316bf

License:

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.

History

Date received : 11 August 2023

Date accepted : 14 October 2023

Funding

Funded by: FundRef http://dx.doi.org/10.13039/501100001809, National Natural Science Foundation of China;

Award ID: 32171285

Award ID: 32101206

Award Recipient : Yifei Lin Jin Huang

Funded by: FundRef http://dx.doi.org/10.13039/501100004829, Department of Science and Technology of Sichuan Province;

Award ID: 2023YFS0025

Award ID: 2023YFS0102

Award Recipient : Yifei Lin Jin Huang

Funded by: FundRef http://dx.doi.org/10.13039/501100013365, West China Hospital, Sichuan University;

Award ID: 2023HXFH044

Award Recipient : Jin Huang

Custom metadata

ScienceOpen disciplines: Nephrology

Keywords: periodontitis,immunity,urologic neoplasms,genetic epidemiology,mendelian randomization,causal relationship

Data availability:

ScienceOpen disciplines: Nephrology

Keywords: periodontitis, immunity, urologic neoplasms, genetic epidemiology, mendelian randomization, causal relationship

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Patients with periodontitis might increase the risk of urologic cancers: a bidirectional two-sample Mendelian randomization study

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Abstract

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Supplementary Information

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Karger: Nephrology

Most cited references 50

Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries

Cancer statistics, 2022

METAL: fast and efficient meta-analysis of genomewide association scans

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