A Bidirectional Mendelian Randomization Analysis of the Causal Relationship Between Inflammatory Bowel Disease and Breast Cancer Based on Estrogen Receptor Status

Overview

Journal Discov Oncol

Publisher Springer

Specialty Oncology

Date 2024 Nov 7

PMID 39508980

Authors

Xindi Ma

Shang Wu

Xiangmei Zhang

Kaiye Du

Chenhui Yang

Sinuo Gao

Yunjiang Liu

Affiliations

Soon will be listed here.

Abstract

The incidence of patients diagnosed with either breast cancer (BC) or inflammatory bowel disease (IBD) is increasing each year. IBD has been shown to be strongly associated with the development of a variety of solid tumors, but the relationship with breast cancer is not yet definitive. We explored the causative relationship between IBD and BC using a Mendelian randomization (MR) strategy. MR-Egger regression, weighted median (WM), simple median (SM), maximum likelihood (ML), and inverse variance weighting (IVW) methods were among the analytical techniques used in this work. The examination of heterogeneity was conducted by the use of Cochran's Q test and Rucker's Q test. The sensitivity analysis in this study used the IVW and MR-Egger methodologies. The results of our investigation suggested that IBD had a beneficial impact on estrogen receptor-negative (ER-) breast cancer (odds ratio (OR) = 0.92, P = 0.02). The study did not find a significant association between IBD and the risk of developing overall breast cancer (OR = 0.99, P = 0.60), as well as estrogen receptor-positive (ER+) breast cancer (OR = 1.02, P = 0.60) specifically. In addition, our study findings indicated that there was a detrimental association between ER+ breast cancer and IBD as determined using reverse MR analysis (OR = 1.07, P = 0.04). Furthermore, this analysis failed to observe any significant association between overall breast cancer (OR = 1.07, P = 0.07) or ER- breast cancer (OR = 0.99, P = 0.89) and IBD. Our bidirectional MR study yielded a correlation between IBD and some specific hormone receptor status of BC.

References

Loconte N, Gershenwald J, Thomson C, Crane T, Harmon G, Rechis R . Lifestyle Modifications and Policy Implications for Primary and Secondary Cancer Prevention: Diet, Exercise, Sun Safety, and Alcohol Reduction. Am Soc Clin Oncol Educ Book. 2018; 38:88-100. DOI: 10.1200/EDBK_200093. View

Ananthakrishnan A, Bernstein C, Iliopoulos D, MacPherson A, Neurath M, Raja Ali R . Environmental triggers in IBD: a review of progress and evidence. Nat Rev Gastroenterol Hepatol. 2017; 15(1):39-49. DOI: 10.1038/nrgastro.2017.136. View

De Rose F, Meduri B, De Santis M, Ferro A, Marino L, Colciago R . Rethinking breast cancer follow-up based on individual risk and recurrence management. Cancer Treat Rev. 2022; 109:102434. DOI: 10.1016/j.ctrv.2022.102434. View

Betteridge J, Armbruster S, Maydonovitch C, Veerappan G . Inflammatory bowel disease prevalence by age, gender, race, and geographic location in the U.S. military health care population. Inflamm Bowel Dis. 2013; 19(7):1421-7. DOI: 10.1097/MIB.0b013e318281334d. View

Parikh-Patel A, White R, Allen M, Cress R . Cancer risk in a cohort of patients with systemic lupus erythematosus (SLE) in California. Cancer Causes Control. 2008; 19(8):887-94. PMC: 4357418. DOI: 10.1007/s10552-008-9151-8. View

Herrera-Gomez R, Grecea M, Gallois C, Boige V, Pautier P, Pistilli B . Safety and Efficacy of Bevacizumab in Cancer Patients with Inflammatory Bowel Disease. Cancers (Basel). 2022; 14(12). PMC: 9220809. DOI: 10.3390/cancers14122914. View

Englund G, Jacobson A, Rorsman F, Artursson P, Kindmark A, Ronnblom A . Efflux transporters in ulcerative colitis: decreased expression of BCRP (ABCG2) and Pgp (ABCB1). Inflamm Bowel Dis. 2007; 13(3):291-7. DOI: 10.1002/ibd.20030. View

Jess T, Gamborg M, Matzen P, Munkholm P, Sorensen T . Increased risk of intestinal cancer in Crohn's disease: a meta-analysis of population-based cohort studies. Am J Gastroenterol. 2006; 100(12):2724-9. DOI: 10.1111/j.1572-0241.2005.00287.x. View

van der Giessen J, van der Woude C, Peppelenbosch M, Fuhler G . A Direct Effect of Sex Hormones on Epithelial Barrier Function in Inflammatory Bowel Disease Models. Cells. 2019; 8(3). PMC: 6468635. DOI: 10.3390/cells8030261. View

10.

Lubian Lopez D, Butron Hinojo C, Castillo Lara M, Sanchez-Prieto M, Sanchez-Borrego R, Mendoza Ladron de Guevara N . Relationship of breast volume, obesity and central obesity with different prognostic factors of breast cancer. Sci Rep. 2021; 11(1):1872. PMC: 7820412. DOI: 10.1038/s41598-021-81436-9. View

11.

Nazari S, Mukherjee P . An overview of mammographic density and its association with breast cancer. Breast Cancer. 2018; 25(3):259-267. PMC: 5906528. DOI: 10.1007/s12282-018-0857-5. View

12.

Amadou A, Torres Mejia G, Fagherazzi G, Ortega C, Angeles-Llerenas A, Chajes V . Anthropometry, silhouette trajectory, and risk of breast cancer in Mexican women. Am J Prev Med. 2014; 46(3 Suppl 1):S52-64. DOI: 10.1016/j.amepre.2013.10.024. View

13.

Lutgens M, van Oijen M, van der Heijden G, Vleggaar F, Siersema P, Oldenburg B . Declining risk of colorectal cancer in inflammatory bowel disease: an updated meta-analysis of population-based cohort studies. Inflamm Bowel Dis. 2013; 19(4):789-99. DOI: 10.1097/MIB.0b013e31828029c0. View

14.

Wagtmans M, Verspaget H, Lamers C, van Hogezand R . Gender-related differences in the clinical course of Crohn's disease. Am J Gastroenterol. 2001; 96(5):1541-6. DOI: 10.1111/j.1572-0241.2001.03755.x. View

15.

Ortizo R, Lee S, Nguyen E, Jamal M, Bechtold M, Nguyen D . Exposure to oral contraceptives increases the risk for development of inflammatory bowel disease: a meta-analysis of case-controlled and cohort studies. Eur J Gastroenterol Hepatol. 2017; 29(9):1064-1070. DOI: 10.1097/MEG.0000000000000915. View

16.

Aguilera-Lizarraga J, Florens M, Viola M, Jain P, Decraecker L, Appeltans I . Local immune response to food antigens drives meal-induced abdominal pain. Nature. 2021; 590(7844):151-156. PMC: 7610810. DOI: 10.1038/s41586-020-03118-2. View

17.

Davies N, Holmes M, Davey Smith G . Reading Mendelian randomisation studies: a guide, glossary, and checklist for clinicians. BMJ. 2018; 362:k601. PMC: 6041728. DOI: 10.1136/bmj.k601. View

18.

Hovde O, Hoivik M, Henriksen M, Solberg I, Smastuen M, Moum B . Malignancies in Patients with Inflammatory Bowel Disease: Results from 20 Years of Follow-up in the IBSEN Study. J Crohns Colitis. 2017; 11(5):571-577. DOI: 10.1093/ecco-jcc/jjw193. View

19.

Rosato V, Bosetti C, Talamini R, Levi F, Montella M, Giacosa A . Metabolic syndrome and the risk of breast cancer in postmenopausal women. Ann Oncol. 2011; 22(12):2687-2692. DOI: 10.1093/annonc/mdr025. View

20.

Bernatsky S, Ramsey-Goldman R, Foulkes W, Gordon C, Clarke A . Breast, ovarian, and endometrial malignancies in systemic lupus erythematosus: a meta-analysis. Br J Cancer. 2011; 104(9):1478-81. PMC: 3101932. DOI: 10.1038/bjc.2011.115. View