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      J-shaped association between uric acid and breast cancer risk: a prospective case–control study

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          Abstract

          Background/aim

          In terms of breast cancer risk, there is no consensus on the effect of uric acid (UA) levels. The aim of our study was to clarify the link between UA and breast cancer risk in a prospective case–control study and to find the UA threshold point.

          Methods

          We designed a case–control study with 1050 females (525 newly diagnosed breast cancer patients and 525 controls). We measured the UA levels at baseline and confirmed the incidence of breast cancer through postoperative pathology. We used binary logistic regression to study the association between breast cancer and UA. In addition, we performed restricted cubic splines to evaluate the potential nonlinear links between UA and breast cancer risk. We used threshold effect analysis to identify the UA cut-off point.

          Results

          After adjusting for multiple confounding factors, we found that compared with the referential level (3.5–4.4 mg/dl), the odds ratio (OR) of breast cancer was 1.946 (95% CI 1.140–3.321) ( P < 0.05) in the lowest UA level and 2.245 (95% CI 0.946–5.326) ( P > 0.05) in the highest level. Using the restricted cubic bar diagram, we disclosed a J-shaped association between UA and breast cancer risk ( P-nonlinear < 0.05) after adjusting for all confounders. In our study, 3.6 mg/dl was found to be the UA threshold which acted as the optimal turning point of the curve. The OR for breast cancer was 0.170 (95% CI 0.056–0.512) to the left and 1.283 (95% CI 1.074–1.532) to the right of 3.6 mg/dl UA ( P for log likelihood ratio test < 0.05).

          Conclusion

          We found a J-shaped association between UA and breast cancer risk. Controlling the UA level around the threshold point of 3.6 mg/dl provides a novel insight into breast cancer prevention.

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          Most cited references37

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          Changing profiles of cancer burden worldwide and in China: a secondary analysis of the global cancer statistics 2020

          Wei Cao, Hong-Da Chen, Yi-Wen Yu … (2021)
          Background: Cancer is one of the leading causes of death globally, but its burden is not uniform. GLOBOCAN 2020 has newly updated the estimates of cancer burden. This study summarizes the most recent changing profiles of cancer burden worldwide and in China and compares the cancer data of China with those of other regions. Methods: We conducted a descriptive secondary analysis of the GLOBOCAN 2020 data. To depict the changing global profile of the leading cancer types in 2020 compared with 2018, we extracted the numbers of cases and deaths in 2018 from GLOBOCAN 2018. We also obtained cancer incidence and mortality from the 2015 National Cancer Registry Report in China when sorting the leading cancer types by new cases and deaths. For the leading cancer types according to sex in China, we summarized the estimated numbers of incidence and mortality, and calculated China's percentage of the global new cases and deaths. Results: Breast cancer displaced lung cancer to become the most leading diagnosed cancer worldwide in 2020. Lung, liver, stomach, breast, and colon cancers were the top five leading causes of cancer-related death, among which liver cancer changed from the third-highest cancer mortality in 2018 to the second-highest in 2020. China accounted for 24% of newly diagnosed cases and 30% of the cancer-related deaths worldwide in 2020. Among the 185 countries included in the database, China's age-standardized incidence rate (204.8 per 100,000) ranked 65th and the age-standardized mortality rate (129.4 per 100,000) ranked 13th. The two rates were above the global average. Lung cancer remained the most common cancer type and the leading cause of cancer death in China. However, breast cancer became the most frequent cancer type among women if the incidence was stratified by sex. Incidences of colorectal cancer and breast cancer increased rapidly. The leading causes of cancer death varied minimally in ranking from 2015 to 2020 in China. Gastrointestinal cancers, including stomach, colorectal, liver, and esophageal cancers, contributed to a massive burden of cancer for both sexes. Conclusions: The burden of breast cancer is increasing globally. China is undergoing cancer transition with an increasing burden of lung cancer, gastrointestinal cancer, and breast cancers. The mortality rate of cancer in China is high. Comprehensive strategies are urgently needed to target China's changing profiles of the cancer burden.
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            Uric acid provides an antioxidant defense in humans against oxidant- and radical-caused aging and cancer: a hypothesis.

            B. N. Ames, R Cathcart, E Schwiers … (1981)
            During primate evolution, a major factor in lengthening life-span and decreasing age-specific cancer rates may have been improved protective mechanisms against oxygen radicals. We propose that one of these protective systems is plasma uric acid, the level of which increased markedly during primate evolution as a consequence of a series of mutations. Uric acid is a powerful antioxidant and is a scavenger of singlet oxygen and radicals. We show that, at physiological concentrations, urate reduces the oxo-heme oxidant formed by peroxide reaction with hemoglobin, protects erythrocyte ghosts against lipid peroxidation, and protects erythrocytes from peroxidative damage leading to lysis. Urate is about as effective an antioxidant as ascorbate in these experiments. Urate is much more easily oxidized than deoxynucleosides by singlet oxygen and is destroyed by hydroxyl radicals at a comparable rate. The plasma urate levels in humans (about 300 microM) is considerably higher than the ascorbate level, making it one of the major antioxidants in humans. Previous work on urate reported in the literature supports our experiments and interpretations, although the findings were not discussed in a physiological context.
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              Oxidative Stress and Cancer

              James Klaunig (2019)
              Cancer is considered a major cause of death worldwide. The etiology of cancer is linked to environmental and genetic inheritance causes. Approximately 90 percent of all human cancers have an environmental cause (non-genetic inheritance) predominantly through lifestyle choices (smoking, diet, UV radiation) while the remaining due to infections and chemical exposure. Cancer is a multistage process that involves mutational changes and uncontrolled cell proliferation. Research has firmly established a causal and contributory role of oxidative stress and oxidative damage in cancer initiation and progression.
              Article 0 comments Cited 160 times – based on 0 reviews     Review now
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                Author and article information

                Contributors
                Fuzai Yin: yinfuzai62@163.com
                Journal
                Journal ID (nlm-ta): J Cancer Res Clin Oncol
                Journal ID (iso-abbrev): J Cancer Res Clin Oncol
                Title: Journal of Cancer Research and Clinical Oncology
                Publisher: Springer Berlin Heidelberg (Berlin/Heidelberg )
                ISSN (Print): 0171-5216
                ISSN (Electronic): 1432-1335
                Publication date (Electronic): 30 March 2023
                Publication date PMC-release: 30 March 2023
                Publication date (Print): 2023
                Volume: 149
                Issue: 10
                Pages: 7629-7636
                Affiliations
                [1 ]GRID grid.256883.2, ISNI 0000 0004 1760 8442, Department of Internal Medicine, , Hebei Medical University, ; Shijiazhuang, Hebei China
                [2 ]GRID grid.452878.4, ISNI 0000 0004 8340 8940, Department of Pneumology, , The First Hospital of Qinhuangdao, ; Qinhuangdao, Hebei China
                [3 ]GRID grid.452878.4, ISNI 0000 0004 8340 8940, Department of Gastrology, , The First Hospital of Qinhuangdao, ; Qinhuangdao, Hebei China
                [4 ]GRID grid.452878.4, ISNI 0000 0004 8340 8940, Department of Endocrinology, , The First Hospital of Qinhuangdao, ; Qinhuangdao, Hebei China
                Article
                Publisher ID: 4725
                DOI: 10.1007/s00432-023-04725-y
                PMC ID: 10374747
                PubMed ID: 36995406
                SO-VID: 1e0ef92c-128d-43b5-a60f-363931b08a24
                Copyright © © The Author(s) 2023
                License:

                Open AccessThis 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 : 7 March 2023
                Date accepted : 24 March 2023
                Categories
                Subject: Research
                Custom metadata
                issue-copyright-statement © Springer-Verlag GmbH Germany, part of Springer Nature 2023

                ScienceOpen disciplines: Oncology & Radiotherapy
                Keywords: j-shaped association,uric acid,breast cancer risk,prospective case–control study,restricted cubic spline
                Data availability:
                ScienceOpen disciplines: Oncology & Radiotherapy
                Keywords: j-shaped association, uric acid, breast cancer risk, prospective case–control study, restricted cubic spline

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