Risk of cancer in regular and low meat-eaters, fish-eaters ...

1 Watling et al. BMC Medicine (2022) 20:73. RESEARCH ARTICLE Open Access Risk of cancer in regular and low meat-eaters, fish-eaters , and vegetarians: a prospective analysis of UK Biobank participants Cody Z. Watling* , Julie A. Schmidt, Yashvee Dunneram, Tammy Y. N. Tong, Rebecca K. Kelly, Anika Knuppel, Ruth C. Travis, Timothy J. Key and Aurora Perez Cornago Abstract Background: Following a vegetarian diet has become increasingly popular and some evidence suggests that being vegetarian may be associated with a lower risk of cancer overall.

2 However, for specific cancer sites, the evidence is limited. Our aim was to assess the associations of vegetarian and non-vegetarian diets with risks of all cancer , colorec . tal cancer , postmenopausal breast cancer , and prostate cancer and to explore the role of potential mediators between these associations. Methods: We conducted a prospective analysis of 472,377 UK Biobank participants who were free from cancer at recruitment. Participants were categorised into regular meat-eaters (n = 247,571), low meat-eaters (n = 205,385), fish- eaters (n = 10,696), and vegetarians (n = 8685) based on dietary questions completed at recruitment.

3 Multivariable- adjusted Cox regressions were used to estimate hazard ratios (HR) and 95% confidence intervals (CI) for all cancer incidence and separate cancer sites across diet groups. Results: After an average follow-up of years, 54,961 incident cancers were identified, including 5882 colorectal, 7537 postmenopausal breast , and 9501 prostate cancers. Compared with regular meat-eaters, being a low meat-eater, fish-eater, or vegetarian were all associated with a lower risk of all cancer (HR: , 95% CI: ; , ;. , , respectively).

4 Being a low meat-eater was associated with a lower risk of colorectal cancer in compari . son to regular meat-eaters ( , ); however, there was heterogeneity in this association by sex (p = ), with an inverse association across diet groups in men, but not in women. Vegetarian postmenopausal women had a lower risk of breast cancer ( , ), which was attenuated and non-significant after adjusting for body mass index (BMI; , ); in mediation analyses, BMI was found to possibly mediate the observed association. In men, being a fish-eater or a vegetarian was associated with a lower risk of prostate cancer ( , and , , respectively).

5 Conclusion: The lower risk of colorectal cancer in low meat-eaters is consistent with previous evidence suggest . ing an adverse impact of meat intake. The lower risk of postmenopausal breast cancer in vegetarian women may be explained by their lower BMI. It is not clear whether the other differences observed for all cancers and for prostate *Correspondence: cancer Epidemiology Unit, Nuffield Department of Population Health, University of Oxford, Oxford OX3 7LF, UK. The Author(s) 2022. Open Access This article is licensed under a Creative Commons Attribution International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made.

6 The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http:// creat iveco mmons. org/ licen ses/ by/4. 0/. The Creative Commons Public Domain Dedication waiver (http:// creat iveco.)

7 Mmons. org/ publi cdoma in/ zero/1. 0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data. Watling et al. BMC Medicine (2022) 20:73 Page 2 of 13. cancer reflect any causal relationships or are due to other factors such as residual confounding or differences in can . cer detection. Keywords: Diet, Vegetarian, Pescatarian, Colorectal, breast , Prostate, Cohort, Meat Background sites [8]. Another hypothesised explanation for the lower cancer is a leading cause of death worldwide [1], and in risk of cancer observed amongst vegetarians and fish-eat- the United Kingdom (UK), 28% of all deaths in 2017 were ers is the possible differences in hormone levels [21], such attributable to cancer [2 4].

8 Colorectal, breast , and pros- as insulin-like growth factor-I (IGF-I) and testosterone, tate cancer collectively account for 39% of all new cancer which may be related to their dietary intakes [21 23]. diagnoses in the UK [5], and it has been estimated that Hormone difference may be important as higher levels of nearly 40% of cancer cases may be preventable through IGF-I have been associated with higher risks of colorec- modifiable factors [6, 7]. Although several dietary factors tal, breast , and prostate cancer [24] and higher levels of have been suggested to influence cancer risk, it remains free testosterone have been associated with prostate can- unclear whether dietary patterns are related to the risk of cer [25] and postmenopausal breast cancer [26].

9 Developing cancer [8, 9]. To further understand these relationships, we assessed It has been hypothesised that vegetarian diets, which the associations of diet groups with risks of all, colorec- exclude the consumption of all meat and fish, may be tal, postmenopausal breast , and prostate cancer in the associated with a lower cancer risk. In addition to exclud- UK Biobank, which includes approximately 10,000 fish- ing red and processed meat, which are associated with an eaters, 8000 vegetarians, and nearly 55,000 total incident increased risk of colorectal cancer [8], vegetarians also cancer cases.

10 We additionally aimed to assess the roles generally consume higher amounts of plant foods such of BMI, circulating IGF-I, and calculated free testoster- as fruits, vegetables, and whole grains compared to meat- one as potential mediators of the observed associations eaters [10, 11], which might also contribute to lowering between diet groups and cancer risk. the risk of some site-specific cancers [8]. Evidence from two large cohorts which include a large proportion of Methods vegetarians, the European Prospective Investigation into Study design and participants cancer and Nutrition-Oxford (EPIC-Oxford) and the Potential participants were first identified for the UK.