Adherence to the Paleolithic diet and Paleolithic-like lifestyle reduce the risk of colorectal cancer in the United States: a prospective cohort study

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Abstract

Background

The plant-based paleolithic diet (PD) and the paleolithic-like lifestyle (PLL) may reduce the risk of chronic diseases, including colorectal adenomas. These dietary and lifestyle approaches are proposed to exert their effects through mechanisms such as reducing inflammation, oxidative stress, and insulin levels. However, whether PD and PLL is associated with the risk of colorectal cancer (CRC) has not been determined.

Methods

A cohort of 74,721 individuals who participated in the PLCO study were included in this analysis. Adherence to the PD and PLL was assessed using PD and PLL scores, where higher scores indicated greater adherence. Multivariable Cox models were utilized to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for the risk of CRC and its subsites (proximal colon cancer and distal CRC). Subgroup analyses were conducted to identify potential effect modifiers.

Results

During a mean follow-up of 9.2 years, a total of 694 CRC cases were identified. Participants in the highest compared with the lowest quartiles of PD score had a lower risk of CRC (Q4 vs Q1: HR 0.76, 95% CI 0.61–0.95, P _trend = 0.009) and proximal colon cancer (Q4 vs Q1: HR 0.73, 95% CI 0.55–0.97, P _trend = 0.02). A stronger inverse association was observed for PLL score with the risk of CRC (Q4 vs Q1: HR 0.64, 95% CI 0.51–0.81, P _trend < 0.001), proximal colon (Q4 vs Q1: HR 0.62, 95% CI 0.46–0.83, P _trend = 0.001) and distal CRC (Q4 vs Q1: HR 0.69, 95% CI 0.48–0.98, P _trend = 0.03). Subgroup analyses revealed the inverse association of PD score with the risk of CRC was more pronounced in participants with BMI < 30 (Q4 vs Q1: HR 0.68, 95% CI 0.53–0.87) than in those with BMI ≥ 30 (Q4 vs Q1: HR 1.07, 95% CI 0.68–1.67) ( P _interaction = 0.02).

Conclusions

Our findings suggest that adhering to the PD and PLL could be a new option to reduce CRC risk.

Supplementary Information

The online version contains supplementary material available at 10.1186/s12967-023-04352-8.

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Most cited references 52

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Cancer statistics, 2023

Rebecca L Siegel, Kimberly D Miller, Nikita Sandeep Wagle … (2023)

Each year, the American Cancer Society estimates the numbers of new cancer cases and deaths in the United States and compiles the most recent data on population-based cancer occurrence and outcomes using incidence data collected by central cancer registries and mortality data collected by the National Center for Health Statistics. In 2023, 1,958,310 new cancer cases and 609,820 cancer deaths are projected to occur in the United States. Cancer incidence increased for prostate cancer by 3% annually from 2014 through 2019 after two decades of decline, translating to an additional 99,000 new cases; otherwise, however, incidence trends were more favorable in men compared to women. For example, lung cancer in women decreased at one half the pace of men (1.1% vs. 2.6% annually) from 2015 through 2019, and breast and uterine corpus cancers continued to increase, as did liver cancer and melanoma, both of which stabilized in men aged 50 years and older and declined in younger men. However, a 65% drop in cervical cancer incidence during 2012 through 2019 among women in their early 20s, the first cohort to receive the human papillomavirus vaccine, foreshadows steep reductions in the burden of human papillomavirus-associated cancers, the majority of which occur in women. Despite the pandemic, and in contrast with other leading causes of death, the cancer death rate continued to decline from 2019 to 2020 (by 1.5%), contributing to a 33% overall reduction since 1991 and an estimated 3.8 million deaths averted. This progress increasingly reflects advances in treatment, which are particularly evident in the rapid declines in mortality (approximately 2% annually during 2016 through 2020) for leukemia, melanoma, and kidney cancer, despite stable/increasing incidence, and accelerated declines for lung cancer. In summary, although cancer mortality rates continue to decline, future progress may be attenuated by rising incidence for breast, prostate, and uterine corpus cancers, which also happen to have the largest racial disparities in mortality.

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Colorectal cancer

Evelien Dekker, Pieter Tanis, Jasper Vleugels … (2019)

Several decades ago, colorectal cancer was infrequently diagnosed. Nowadays, it is the world's fourth most deadly cancer with almost 900 000 deaths annually. Besides an ageing population and dietary habits of high-income countries, unfavourable risk factors such as obesity, lack of physical exercise, and smoking increase the risk of colorectal cancer. Advancements in pathophysiological understanding have increased the array of treatment options for local and advanced disease leading to individual treatment plans. Treatments include endoscopic and surgical local excision, downstaging preoperative radiotherapy and systemic therapy, extensive surgery for locoregional and metastatic disease, local ablative therapies for metastases, and palliative chemotherapy, targeted therapy, and immunotherapy. Although these new treatment options have doubled overall survival for advanced disease to 3 years, survival is still best for those with non-metastasised disease. As the disease only becomes symptomatic at an advanced stage, worldwide organised screening programmes are being implemented, which aim to increase early detection and reduce morbidity and mortality from colorectal cancer.

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The microbial metabolites, short-chain fatty acids, regulate colonic Treg cell homeostasis.

Patrick M. Smith, Michael R. Howitt, Nicolai Panikov … (2013)

Regulatory T cells (Tregs) that express the transcription factor Foxp3 are critical for regulating intestinal inflammation. Candidate microbe approaches have identified bacterial species and strain-specific molecules that can affect intestinal immune responses, including species that modulate Treg responses. Because neither all humans nor mice harbor the same bacterial strains, we posited that more prevalent factors exist that regulate the number and function of colonic Tregs. We determined that short-chain fatty acids, gut microbiota-derived bacterial fermentation products, regulate the size and function of the colonic Treg pool and protect against colitis in a Ffar2-dependent manner in mice. Our study reveals that a class of abundant microbial metabolites underlies adaptive immune microbiota coadaptation and promotes colonic homeostasis and health.

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Author and article information

Contributors

Linglong Peng:

ORCID: http://orcid.org/0000-0001-5774-3110

penglinglong_cqmu@cqmu.edu.cn

Ling Xiang: 306359@hospital.cqmu.edu.cn

Journal

Journal ID (nlm-ta): J Transl Med

Journal ID (iso-abbrev): J Transl Med

Title: Journal of Translational Medicine

Publisher: BioMed Central (London )

ISSN (Electronic): 1479-5876

Publication date (Electronic): 19 July 2023

Publication date PMC-release: 19 July 2023

Publication date Collection: 2023

Volume: 21

Electronic Location Identifier: 482

Affiliations

[1 ]GRID grid.412461.4, ISNI 0000 0004 9334 6536, Department of Gastrointestinal Surgery, , The Second Affiliated Hospital of Chongqing Medical University, ; No.288, Tianwen Avenue, Nan’an District, Chongqing, 400010 China

[2 ]GRID grid.412461.4, ISNI 0000 0004 9334 6536, Department of Clinical Nutrition, , The Second Affiliated Hospital of Chongqing Medical University, ; Chongqing, China

Author information

Linglong Peng http://orcid.org/0000-0001-5774-3110

Article

Publisher ID: 4352

DOI: 10.1186/s12967-023-04352-8

PMC ID: 10357623

PubMed ID: 37468920

SO-VID: 1978f820-011a-4165-8364-84dd20fa81e0

License:

Open Access This article is licensed under a Creative Commons Attribution 4.0 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. 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://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.

History

Date received : 25 May 2023

Date accepted : 11 July 2023

Funding

Funded by: FundRef http://dx.doi.org/10.13039/501100011933, Chongqing Science and Technology Foundation;

Award ID: cstc2021jcyj-msxmX0153

Award Recipient : Linglong Peng

Funded by: FundRef http://dx.doi.org/10.13039/501100002865, Chongqing Science and Technology Commission;

Award ID: cstc2021jcyj-msxmX0112

Award ID: CSTB2022NSCQ-MSX1005

Award Recipient : Yaxu Wang Haitao Gu

Funded by: Kuanren Talents Project of the Second Affiliated Hospital of Chongqing Medical University in China

Award ID: kryc-yq-2110

Award Recipient : Haitao Gu

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ScienceOpen disciplines: Medicine

Keywords: paleolithic diet,paleolithic-like lifestyle,colorectal cancer,epidemiology,cohort study

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ScienceOpen disciplines: Medicine

Keywords: paleolithic diet, paleolithic-like lifestyle, colorectal cancer, epidemiology, cohort study

Adherence to the Paleolithic diet and Paleolithic-like lifestyle reduce the risk of colorectal cancer in the United States: a prospective cohort study

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Karger: Oncology

Most cited references 52

Cancer statistics, 2023

Colorectal cancer

The microbial metabolites, short-chain fatty acids, regulate colonic Treg cell homeostasis.

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