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Novel Dietary Index for Gut Microbiota and Associations with Colorectal Cancer and Breast Cancer Risk

Principal Investigator
Name
Susan Steck
Degrees
PhD, MPH, RD, FAND
Institution
University of South Carolina
Position Title
Professor
Email
About this CDAS Project
Study
PLCO (Learn more about this study)
Project ID
PLCO-730
Initial CDAS Request Approval
Jan 28, 2021
Title
Novel Dietary Index for Gut Microbiota and Associations with Colorectal Cancer and Breast Cancer Risk
Summary
Background: Recent studies show that disturbances in the gut microbiota, microorganisms in the human intestine, are a link through which modifiable risk factors induce carcinogenesis of both the colon and breast.1–4 Disturbed gut microbiota, termed dysbiosis, increases the risk for colorectal and breast cancer through effects on inflammation, adiposity, oxidative stress, and estrogen metabolism.5,6 Diet is among the prominent determinants of gut microbiota composition and several health promoting and deleterious effects of diet are, in fact, mediated by the gut microbiota.7–9 Although studies have investigated specific food components that promote or disturb gut microbiota diversity and balance,10–13 there is lack of dietary patterns or indices that define the ideal metabolic requirements of the gut microbiota, which, when met, could result in a suppression of colorectal and breast cancer risk.We are developing a novel dietary index for gut microbiota (DI-GM) based on extensive literature review that will score an individual’s diet quality based on its potential to increase gut microbiota diversity and minimize dysbiosis. Our aim is to utilize the data from PLCO to examine the association of the novel DI-GM and risk of colorectal and breast cancers. Since gut microbiota are involved in estrogen metabolism, we will also explore the association between the DI-GM and serum estrogen metabolite levels among the subset of PLCO female participants with these data.
Method: The main exposure, the DI-GM will be calculated using dietary data from the PLCO diet history questionnaire (DHQ) along with existing dietary indices (Healthy Eating Index (HEI), Mediterranean Diet Score (MDS) and Dietary Approaches to Stop Hypertension (DASH)). The primary outcomes will be incident colorectal cancer and incident breast cancer. We will examine both continuous DI-GM and categorical DI-GM variables, exploring quartiles of DI-GM. Cox proportional hazards models will be used to estimate HRs and 95% confidence intervals (CIs) to evaluate the relationships of DI-GM with colorectal and breast cancer risk. Subgroup analyses will be conducted to explore whether associations differ by breast cancer subtypes. Linear regression will be used to examine the association between the DI-GM and estrogen metabolite levels. Adjustment will be done for potential confounders.
Significance: The findings can lay groundwork for future intervention studies that focus on dietary modulation of gut microbiota to prevent and improve prognosis of colorectal and breast cancers.
Aims

1. Examine the association of the DI-GM and risk of colorectal cancer. (first manuscript)
2. Examine the association of the DI-GM and risk of breast cancer (second manuscript)
- To examine whether the association between the DI-GM and breast cancer risk vary by breast cancer subtypes
- To investigate the association between the DI-GM and blood level of estrogen metabolites
Reference
1. Chen J, Douglass J, Prasath V, et al. The microbiome and breast cancer: a review. Breast Cancer Res Treat. 2019;178(3):493-496. doi:10.1007/s10549-019-05407-5
2. Mani S. Microbiota and Breast Cancer. In: Progress in Molecular Biology and Translational Science. Vol 151. Elsevier B.V.; 2017:217-229. doi:10.1016/bs.pmbts.2017.07.004
3. Yang J, Yu J. The association of diet, gut microbiota and colorectal cancer: what we eat may imply what we get. Protein Cell. 2018;9(5):474-487. doi:10.1007/s13238-018-0543-6
4. Borges-Canha M, Portela-Cidade JP, Dinis-Ribeiro M, Leite-Moreira AF, Pimentel-Nunes P. Role of colonic microbiota in colorectal carcinogenesis: A systematic review. Rev Esp Enfermedades Dig. 2015;107(11):659-671. doi:10.17235/reed.2015.3830/2015
5. Gagnière J, Raisch J, Veziant J, et al. Gut microbiota imbalance and colorectal cancer. World J Gastroenterol. 2016;22(2):501-518. doi:10.3748/wjg.v22.i2.501
6. Komorowski AS, Pezo RC. Untapped “-omics”: the microbial metagenome, estrobolome, and their influence on the development of breast cancer and response to treatment. Breast Cancer Res Treat. 2020;179(2):287-300. doi:10.1007/s10549-019-05472-w
7. O’Keefe SJD. Diet, microorganisms and their metabolites, and colon cancer. Nat Rev Gastroenterol Hepatol. 2016;13(12):691-706. doi:10.1038/nrgastro.2016.165
8. Vipperla K, O’Keefe SJ. Diet, microbiota, and dysbiosis: A “recipe” for colorectal cancer. Food Funct. 2016;7(4):1731-1740. doi:10.1039/c5fo01276g
9. Power SE, O’Toole PW, Stanton C, Ross RP, Fitzgerald GF. Intestinal microbiota, diet and health. Br J Nutr. 2014;111(3):387-402. doi:10.1017/S0007114513002560
10. Tindall AM, Petersen KS, Kris-Etherton PM. Dietary patterns affect the gut microbiome-the link to risk of cardiometabolic diseases. J Nutr. 2018;148(9):1402-1407. doi:10.1093/jn/nxy141
11. Hasan N, Yang H. Factors affecting the composition of the gut microbiota, and its modulation. PeerJ. 2019;2019(8). doi:10.7717/peerj.7502
12. Valdes AM, Walter J, Segal E, Spector TD. Role of the gut microbiota in nutrition and health. BMJ. 2018;361:36-44. doi:10.1136/bmj.k2179
13. O’Keefe SJD, Li J V., Lahti L, et al. Fat, fibre and cancer risk in African Americans and rural Africans. Nat Commun. 2015;6. doi:10.1038/ncomms7342
14. Nguyen LH, Ma W, Wang DD, et al. Association Between Sulfur-Metabolizing Bacterial Communities in Stool and Risk of Distal Colorectal Cancer in Men. Gastroenterology. 2020;158(5):1313-1325. doi:10.1053/j.gastro.2019.12.029

Collaborators

Susan E Steck, University of South Carolina
Bezawit E Kase, University of South Carolina