Objective: If the endogenous acid-base balance is not well regulated, dietary acid load contributes to metabolic acidosis, leading to inflammation and cancer metastasis. Nevertheless, there is still no epidemiologic evidence on the association between diet-dependent acid load and colorectal cancer risk. Therefore, we aim to explore its possible role therein.

Materials and Methods: A case-control study was performed on 611 colorectal cancer incident cases and 2394 age-frequency matched controls, using a specific multi-topic questionnaire, including a food frequency questionnaire. Food-derived nutrients were calculated from available databases. We assessed dietary acid load based on existing and validated measures as potential renal acid load (PRAL) score and net endogenous acid production (NEAP) score. Odds Ratios (ORs) were estimated by logistic regression, adjusting for potential confounders.

Results: We found direct associations between dietary acid load and colorectal cancer risk. The highest quartile of the PRAL score was significantly associated (OR=1.53, p_trend = 0.03). A positive family history of cancer and female sex derived even higher risks (OR=2.31 and OR=2.23, respectively). Nevertheless, no heterogeneities were found in these strata. The NEAP score tended to display similar associations.

Conclusions: PRAL and NEAP scores are directly associated with meat intake and inversely associated with plant-based foods intake. Results suggest that a low acid load dietary style may reduce colorectal cancer risk, which agrees with studies focused on food groups and dietary patterns. To our knowledge, the present one is the first reported epidemiologic study on dietary acid load and colorectal cancer risk.