High-protein diet scores, macronutrient substitution, and breast cancer risk: insights from substitution analysis

Evidence from recent studies suggested that variation in the quantity and quality of macronutrients in the diet may potentially play a role in predicting the risk of breast cancer (BC). In the current study, we aimed to assess the association of different high-protein diet scores and replacing fats and carbohydrate (CHO) with protein in the diet with the BC risk among Iranian women.

The current hospital-based case-control study was conducted on 401 participants, aged ≥ 30 years old, including 134 women in the case group who had been diagnosed with histologically confirmed BC and 267 women in the control group. Dietary intake data was collected using a validated food frequency questionnaire, and high protein diet scores were determined. Logistic regression models were used to determine the odds ratios (OR) and 95% confidence interval (CI) of BC across tertiles of high protein diet scores. Also, we assessed how substituting protein with other macronutrients affected BC odds while adjusting for the various confounding variables.

Participants' mean ± SD of age and body mass index were 47.9 ± 10.3 years and 29.4 ± 5.5 kg/m², respectively. The scores of high-protein-low-CHO and fat diet, high-protein and CHO-low-fat diet, and high-protein and fat-low-CHO diet in participants were 16.5 ± 3.8, 16.5 ± 6.7, and 16.4 ± 5.9, respectively. In the multivariable model, individuals in the highest tertile of high-protein-low-CHO and fat diet score (OR:0.71;95%CI:0.56-0.90) and high-protein and CHO-low-fat diet (OR:0.76;95%CI:0.60-0.97) had lower odds of BC compared to those in the lowest tertile (P < 0.05). However, no significant association was found between high-protein and fat-low-CHO diet and BC risk. Our results showed that replacing fat by protein (OR_differences:-0.40;95%CI:-0.73,-0.07) and also replacing refined-CHO by plant protein (OR_differences:-0.66;95%CI:-1.26,-0.07) in the diet are associated inversely with risk of BC(P < 0.05).

The results of our study suggested that higher adherence to a high-protein-low-CHO and fat diet, characterized by a higher intake of plant proteins and a lower intake of refined grains and saturated fat can play a protective role against the odds of BC.