Discussion

The results of this case-control study showed that dietary acid load assessed by both PRAL and NEAP, was significantly associated with the higher risk of PC. The association between some nutrients and risk of PC have been investigated previously (40-50). It seems that dietary intake is the largest external or environmental epigenetic factor capable of driving the development or maintenance of cancer (51). This study for the first time showed a positive association between DAL and risk of PC. In line with our findings, some studies revealed that acidic environment and dietary acid load could contribute to cancer development. (35, 52-56). However, some other studies did not support these findings (35). Regarding to some specific types of cancer, previous research showed a significant positive association between net acid excretion and bladder cancer risk (57). In the other study, Yong-Moon Mark Park et al.(58) found higher risk of invasive and metastatic potential of breast cancer in relation to diet-dependent acid load in a nationwide large prospective cohort study (58). Besides, higher cancer mortality was associated with metabolic acid load, measured by lower serum bicarbonate (59). Mechanistically, some studies showed that carcinogenesis due to metabolic acidosis may occur through some intermediary effects (51). Metabolic acidosis, especially caused by dietary acid loads, can stimulate cancer metastasis, because of reduced buffering capacity of patients with cancer (60-63). Some studies on patients with cancer also showed changes in PH in the cancerous cells and their microenvironment, in such a way that intracellular pH (pHi) increased compared to normal cells (∼7.4 versus ∼7.2), while extracellular pH (pHe) decreased (∼6.7–7.1 versus ∼7.4) (64, 65). On the other hand, several studies have shown that different types of acid load interventions, such as dietary changes (66) or taking bicarbonate (67) or phosphate salt (68), could affect the pH of the urine, but not the pH of the blood. Generally, diet has potential to cause metabolic acidosis through affecting acid-base balance and producing acid or alkaline precursors (69-71), and consuming acidogenic diets could promote higher urinary acid excretion in comparison to alkalizing foods (72). Therefore, it seems that highlighting the roles of dietary acid load in relation to the cancer pathogenesis and performing most comprehensive studies to determine exact associations would be necessary.
This study had some strengths: First, this is the first study investigating the association between dietary acid load and risk of PC. Second, we used newly diagnosed cases to remove the effects of the patients’ dietary intake changes on the cancer risk. Third, several confounders were adjusted in the statistical models which increase the possibility of the findings. Our study also had some limitations: First, however we used a validated semi-quantitate FFQ, response errors, recall bias, and social desirability are inevitable in gathering data using FFQ. Second, the probability of selection bias in case-control studies cannot be avoided and similar to all case–control studies, no cause and effect association could be interpreted between DAL and PC. Third, although we matched cases and controls by age and body mass index and adjusted the findings for several confounders, always there are some residual confounders, which might affect our findings.
In conclusion, the results of this study suggest that DAL could increase the risk of prostate cancer. However, further comprehensive prospective studies with larger sample size and longer duration are needed to confirm these findings.