PUBLICATION ABSTRACT

The association between animal protein, plant protein, and their substitution with bladder cancer risk: a pooled analysis of 10 cohort studies

Beigrezaei S, Dianati M, Salehi-Abargouei A, Fararouei M, Akbari-Beni A, Brinkman M, White E, Weiderpass E, Le Calvez-Kelm F, Gunter MJ, Huybrechts I, Liedberg F, Skeie G, Tjonneland A, Riboli E, Zeegers MP, Wesselius A. The association between animal protein, plant protein, and their substitution with bladder cancer risk: a pooled analysis of 10 cohort studies. Eur J Nutr. 2024 Dec 24;64(1):55. doi: 10.1007/s00394-024-03551-3. PMID: 39718625; PMCID: PMC11668844.

Abstract

Purpose: Although total dietary protein intake has been associated with bladder cancer (BC) risk, the effect of the origin (plant or animal) and the substitutions remain to be understood. This study aimed to investigate the effect of total dietary protein, animal-based protein, plant-based protein, and their substitutions with each other on the risk of BC using a pooled analysis of 10 cohort studies.

Methods: The study was conducted within the “BLadder cancer Epidemiology and Nutritional Determinants” (BLEND) study, including 10 prospective cohort studies from several European countries, the United Kingdom, and the United States. Individual data from 10 prospective cohorts containing 434,412 participants (overall male/female ratio was almost 3:1) with a total of 4,224,643.8 person-years of follow-up was analyzed. Hazard ratios (HRs) and 95% confidence intervals (CIs) for BC risk for animal and plant-based protein substitutions of 30gram (g) per day (g/day) were estimated by multivariable adjusted HRs using Cox proportional hazards models.

Results: During 11.4 years of follow-up, among 434,412 participants (73.28% female), 1,440 new cases of BC were identif ied. After multivariable adjustment, no association was observed between the intake of total, animal-based protein, and plant-based protein and BC risk. Replacement of every 30 g/day of animal-based protein intake by the same amount of plantbased protein intake or vice versa was not associated with the risk of BC. Conclusion In conclusion, our study found no association between protein intake—whether from animal or plant sources— and the risk of BC. Substituting animal-based protein with plant-based protein, or the reverse, did not influence BC risk. Future studies are required to provide information on the link between animal- and plant-based proteins and BC risk.

Keywords: Total proteins · Plant-based proteins · Animal-based proteins · Bladder cancer · Substitution analysis · Replacement · Cohort studies

Introduction

Bladder cancer (BC) is the 10th most common and 13th most deadly neoplasm worldwide, and the number of incident cases and deaths related to the condition is still rising [1, 2], particularly in Europe and other developed nations. The incidence rate of BC and its mortality is approximately four times higher in men than in women [2]. Due to the high recurrence rate of BC and the ongoing invasive monitoring requirement, BC has the highest per patient lifetime treatment costs of all cancers, posing a remarkable financial burden on the healthcare systems [3, 4]. New preventive and management strategies are, therefore, highly needed [5]. Previous epidemiologic research has demonstrated that most BC cases are attributable to tobacco use, male sex, age, obesity, and occupational exposures [6–8]. In addition, as for many cancers, the association of various dietary factors with BC has been studied [9–11], and the results were supportive of the benefits of consuming more vegetables and fruits [12], dairy products [13], and tea [14]. However, despite the currently available evidence on the association between diet and BC risk, a recent report by the World Cancer Research Fund International (WCRF) declared that the evidence is still scarce [15]. Dietary protein intake has been a high-priority research topic of interest in nutritional research [16]. It has been demonstrated that even small changes in the amount or combination of protein intake in individuals can have a big impact on public health [17, 18]. Evidence from prospective cohort studies has demonstrated that different sources of dietary protein might have the potential to affect the development of several chronic diseases [19, 20]. There are also some previous studies on different sources of protein and BC risk [21, 22]. Several prospective cohort studies have shown an increased risk of BC associated with increased consumption of red and processed meat [21, 23]. In contrast, Dianatinasab et al. [24] reported an elevated risk of BC specifically linked to high organ meat intake, while no significant associations were observed for other meat sources. Similarly, a Swedish cohort study found no significant association between the intake of red and processed meat, poultry, or fish and BC risk [22]. Despite prior research on the associations between the intake of different protein sources and BC risk, the overall results remain inconclusive. Dietary proteins are macronutrients that are classified as animal and plant origins [25]. Proteins originating from animal or plant sources have different combinations of amino acids and dietary compounds with potentially various health effects [26]. In nutritional epidemiology, dietary substitution methods are used to evaluate the impact of replacing specific foods with other foods of equivalent amounts on the risk of disease development [27]. Substitution analyses provide a statistical framework that models dietary modifications by altering macronutrient composition while maintaining constant total energy intake, thereby helping to identify optimal dietary patterns. To our best knowledge, previous studies have not focused on the effect of different origins of dietary protein and their replacement on BC risk and data on the theoretical effects of substituting protein sources on the risk of BC is limited. Therefore, the present study aimed to investigate the effect of total, animal, and plant-based proteins, as well as their replacement, on the risk of developing BC, by using the pooled data of 10 cohort studies.

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