Investigating the Anti-inflammatory Effect of Allopurinol on the Prevention of Prostate Cancer

Introduction Gout is a form of arthritis that arises from the accumulation of uric acid in the bloodstream. Allopurinol, a medication that reduces uric acid levels, has also been shown to have anti-inflammatory effects. Research in this area seems to have mixed results. Furthermore, limited research has examined the relationship between gout treated with Allopurinol and its possible protective factors against prostate cancer. The purpose of this study was to examine the relationship between Allopurinol use and prostate cancer, controlling for demographic and metabolic factors. Methods Information was collected from the National Health and Nutrition Examination Survey (NHANES) dataset of the Centers for Disease Control and Prevention (CDC). Logistic regression analysis was employed to establish the correlation between the usage of Allopurinol and the occurrence of prostate cancer while considering variables such as weight, hypertension, hyperlipidemia, race, educational level, and marital status. The research received approval from the review board of the Physician's Journal of Medicine. Results We found no significant association between Allopurinol use and prostate cancer, controlling for covariates. Age was found to have a positive association with prostate cancer. Marriage was found to have a negative association with prostate cancer. Conclusion The results of this study did not find a significant association between Allopurinol use and the risk of prostate cancer. However, this study adds to the limited body of research examining the relationship between gout, Allopurinol, and prostate cancer and suggests that further research is needed in this area. Overall, while Allopurinol has been shown to have anti-inflammatory effects and is used to treat gout, its use does not appear to have a significant impact on the risk of developing prostate cancer.


Introduction
Gout is a form of arthritis that arises from the accumulation of uric acid in the bloodstream. This buildup leads to the formation of small crystals that deposit in the joints, causing pain, swelling, redness, and warmth. Over time, gout can cause joint damage, erosions, and tophi to form. Gout is often treated with medication that reduces uric acid production and removes it from the body, along with pain relief and antiinflammatory drugs. Allopurinol is a medication that is used to reduce the levels of uric acid in the body. In addition to its role in reducing uric acid levels, Allopurinol has been shown to have anti-inflammatory effects [1,2].
Some studies suggest that the use of anti-inflammatory medications may be associated with a lower risk of prostate cancer or with improved outcomes for men with prostate cancer [3][4][5][6]. However, other studies have found no significant relationship between anti-inflammatory medication use and prostate cancer occurrence and mortality [7,8]. This raises the question as to whether Allopurinol may decrease the risk of prostate cancer either in its uric acid-lowering effects or its anti-inflammatory effects.
There is limited research examining the relationship between gout treated with Allopurinol and its possible protective factors against prostate cancer. Some studies have shown that gout may be associated with prostate cancer [9][10][11]. One study even identified a potential mechanism of the relationship between gout and prostate cancer demonstrating that a change in plasma or intracellular urate levels has an impact on prostate cancer cell growth [12]. This indicated that the use of uric acid-lowering agents, such as Allopurinol, would potentially be therapeutic in the prevention of prostate cancer.
However, though gout was shown to be correlated to prostate cancer [11], the definition of gout was those treated with Allopurinol. This indicates that while gout may be a risk factor for prostate cancer, treatment with Allopurinol did not mitigate this risk. Additionally, previous studies have found no clear association between Allopurinol use and prostate cancer risk [13,14].
In light of the above, there is much need to investigate the relationship between Allopurinol and prostate cancer. The objective of this study was to investigate the correlation between the utilization of Allopurinol and prostate cancer, taking into account demographic variables, such as age, race, and BMI, as well as factors related to gout and metabolic syndrome, including heart disease, hypertension, and diabetes. . Logistic regression analysis was conducted to investigate the association between the usage of Allopurinol and the history of prostate cancer while controlling for variables such as weight, hypertension, hyperlipidemia, race, educational level, and marital status. The primary outcome variable in this study was the presence of a prostate cancer history, determined by a positive response to the question "Ever told you had cancer or malignancy," with "prostate" as the specific response to the subsequent question "What kind was it?" This was coded as True for "Yes" and False for "No." The predictor variable utilized was Allopurinol usage, assessed through the response to the question "In the past 30 days, have you used or taken medication for which a prescription is needed?" A response of "Allopurinol" was coded as True. Covariates, including BMI, age, race, educational level, and marital status, were also examined. Furthermore, other factors associated with both prostate cancer and inflammation, such as blood pressure and low-density lipoprotein, were controlled for in the analysis.

Statistical analysis
To assess the correlation between the predictor and outcome variables mentioned earlier, a multivariate logistic regression analysis was conducted to examine the association between the utilization of Allopurinol and the presence of a prior prostate cancer diagnosis. The variables taken into account in the analysis encompassed but were not limited to weight, age, race, educational level, and marital status. Calculations were performed to determine the adjusted odds ratios (OR), coefficients of association (B), and confidence intervals (CI). All analyses were performed using IBM SPSS Statistics for Windows, Version 28.0 (Released 2021; IBM Corp., Armonk, New York, United States).

Results
Our study found that there was no significant association between Allopurinol use and prostate cancer, OR (odds ratio) = 1.764, CI (confidence interval) = -0.938 -2.075. Other variables were found to be significant. Age was found to have a positive association with prostate cancer, meaning higher age was associated with a higher rate of prostate cancer, as previously well-established. Being married was found to have a negative association with prostate cancer, meaning being married was associated with a lower rate of prostate cancer (Tables 1, 2). This too is consistent with prior literature [15,16].   In summary, the study did not find a significant association between Allopurinol use and prostate cancer. However, we found that higher age was associated with a higher rate of prostate cancer and being married was associated with a lower rate of prostate cancer.

Discussion
The data regarding Allopurinol use and its potential effects on prostate cancer incidence are conflicting. The reason for this is that it is known that Allopurinol has anti-inflammatory effects [1,2]. Some studies suggest that anti-inflammatory medications may be associated with a lower risk of prostate cancer [3,4].
However, other studies have found no significant relationship between anti-inflammatory medication use and prostate cancer occurrence and mortality [7,8]. For this reason, our study aimed to investigate the relationship between Allopurinol use and prostate cancer. We controlled for demographic factors such as age, race, marital status, and BMI. We also controlled for factors well-established to be associated with gout and metabolic syndrome since these factors would likely be an underlying cause of prostate cancer and mask the relationship between Allopurinol and prostate cancer alone [17].
Our findings, which showed no significant association between Allopurinol use and prostate cancer occurrence after adjusting for covariates, are consistent with previous research on this topic [18]. However, some previous studies have suggested a potential link between Allopurinol use and a reduced risk of prostate cancer [19,20]. It is possible that the anti-inflammatory effects of Allopurinol are not sufficient to impact prostate cancer risk or that other factors may be involved in the relationship between gout and prostate cancer.
It is important to note that our study has some limitations. The data used in our analysis is based on selfreported information, which may not always be accurate. In addition, the sample size of our study is relatively small, which may limit the generalizability of our findings. In addition, although the study controlled for several confounding variables, there may be other unmeasured factors that could affect the relationship between Allopurinol use and prostate cancer occurrence. Lastly, the study was observational and therefore cannot establish causality. Despite these limitations, this investigation contributes to the existing literature on the relationship between Allopurinol use and prostate cancer by providing further evidence on this topic.

Conclusions
In conclusion, our study did not find a significant relationship between Allopurinol use and prostate cancer risk. While previous research has suggested that gout may be associated with prostate cancer, our results indicate that treatment with Allopurinol may not be sufficient to mitigate this risk.
Further research is needed to investigate the potential link between gout and prostate cancer, as well as the potential benefits of other medications used to treat gout in relation to prostate cancer risk. Our study highlights the importance of considering multiple factors when examining the relationship between medications and cancer risk, including demographic and health-related factors that may impact this relationship.

Additional Information Disclosures
Human subjects: Consent was obtained or waived by all participants in this study. The Institutional Review Board of Physicians Journal of Medicine issued approval 0011346. Animal subjects: All authors have confirmed that this study did not involve animal subjects or tissue. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work.