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.