{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T11:55:40Z","timestamp":1785412540873,"version":"3.56.0"},"reference-count":175,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2026,6,5]],"date-time":"2026-06-05T00:00:00Z","timestamp":1780617600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003196","name":"Ministero Italiano della Salute","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100003196","id-type":"DOI","asserted-by":"crossref"}]},{"id":[{"id":"https:\/\/ror.org\/00789fa95","id-type":"ROR","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100015550","name":"European Union","doi-asserted-by":"publisher","award":["PNRR-MAD-2022-12375679"],"award-info":[{"award-number":["PNRR-MAD-2022-12375679"]}],"id":[{"id":"10.13039\/501100015550","id-type":"DOI","asserted-by":"publisher"}]},{"award":["PNRR-MAD-2022-12375679"],"award-info":[{"award-number":["PNRR-MAD-2022-12375679"]}],"id":[{"id":"https:\/\/ror.org\/019w4f821","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Colorectal cancer (CRC) is the third most diagnosed malignancy and the second leading cause of cancer-related mortality worldwide. A consistent and epidemiologically well-documented feature of CRC is its sexual dimorphism: age-standardized incidence rates are 33\u201345% higher in men than in women, and mortality rates differ by 43\u201350%. Beyond epidemiology, biological sex influences tumor location, molecular subtype, and clinical outcome. Women more frequently develop right-sided, microsatellite-unstable tumors driven by the CpG island methylator phenotype pathway, whereas men predominantly present with left-sided, chromosomally unstable tumors harboring APC, KRAS, and TP53 mutations. Sex steroid hormones play a central modulatory role: estrogens, primarily via estrogen receptor \u03b2 (ER\u03b2), exert tumor-suppressive effects on colonic epithelium, whereas androgens promote pro-inflammatory and pro-tumorigenic signaling through androgen receptor (AR)-dependent pathways. The gut microbiome displays sex-specific compositional profiles (\u2018microgenderome\u2019) and contributes to sex-specific CRC susceptibility through bidirectional interactions with sex hormones, shaping distinct immunological and metabolic microenvironments. Finally, sex influences the pharmacokinetics of fluoropyrimidines, the toxicity of targeted agents, and the response to immune checkpoint inhibitors. This review summarizes current evidence on sex-related differences in CRC epidemiology, molecular pathology, hormonal regulation, gut microbiota composition, and treatment outcomes, highlighting the need to systematically incorporate sex as a biological variable in CRC research and clinical practice.<\/jats:p>","DOI":"10.3390\/cells15111039","type":"journal-article","created":{"date-parts":[[2026,6,5]],"date-time":"2026-06-05T14:10:42Z","timestamp":1780668642000},"page":"1039","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Exploring Risk Factors and Sex Differences in Colorectal Cancer: Insights from Current Evidence"],"prefix":"10.3390","volume":"15","author":[{"given":"Camilla","family":"Cittadini","sequence":"first","affiliation":[{"name":"Department of Infectious Diseases, Italian National Institute of Health, Viale Regina Elena, 299-00161 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7221-9173","authenticated-orcid":false,"given":"Elisabetta","family":"Iessi","sequence":"additional","affiliation":[{"name":"Center for Gender-Specific Medicine, Italian National Institute of Health, Viale Regina Elena, 299-00161 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4501-8661","authenticated-orcid":false,"given":"Rosa","family":"Vona","sequence":"additional","affiliation":[{"name":"Center for Gender-Specific Medicine, Italian National Institute of Health, Viale Regina Elena, 299-00161 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5477-3752","authenticated-orcid":false,"given":"Paola","family":"Matarrese","sequence":"additional","affiliation":[{"name":"Center for Gender-Specific Medicine, Italian National Institute of Health, Viale Regina Elena, 299-00161 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,6,5]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Pandey, H., Tang, D.W.T., Wong, S.H., and Lal, D. (2023). Gut Microbiota in Colorectal Cancer: Biological Role and Therapeutic Opportunities. Cancers, 15.","DOI":"10.3390\/cancers15030866"},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Tsokkou, S., Konstantinidis, I., Papakonstantinou, M., Chatzikomnitsa, P., Liampou, E., Toutziari, E., Giakoustidis, D., Bangeas, P., Papadopoulos, V., and Giakoustidis, A. (2025). Sex Differences in Colorectal Cancer: Epidemiology, Risk Factors, and Clinical Outcomes. J. Clin. Med., 14.","DOI":"10.3390\/jcm14155539"},{"key":"ref_3","first-page":"87","article-title":"Global cancer statistics, 2012","volume":"65","author":"Torre","year":"2015","journal-title":"CA Cancer J. Clin."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"683","DOI":"10.1136\/gutjnl-2015-310912","article-title":"Global patterns and trends in colorectal cancer incidence and mortality","volume":"66","author":"Arnold","year":"2017","journal-title":"Gut"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"256","DOI":"10.5534\/wjmh.230085","article-title":"Sex Difference of Colon Adenoma Pathway and Colorectal Carcinogenesis","volume":"42","author":"Choi","year":"2024","journal-title":"World J. Men\u2019s Health"},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"Harvey, B.J., and Harvey, H.M. (2023). Sex Differences in Colon Cancer: Genomic and Nongenomic Signalling of Oestrogen. Genes, 14.","DOI":"10.3390\/genes14122225"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"167","DOI":"10.1186\/s12964-024-01549-2","article-title":"Sex differences in colorectal cancer: With a focus on sex hormone-gut microbiome axis","volume":"22","author":"Wu","year":"2024","journal-title":"Cell Commun. Signal."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"101204","DOI":"10.1016\/j.esmoop.2023.101204","article-title":"Sex and gender perspectives in colorectal cancer","volume":"8","author":"Baraibar","year":"2023","journal-title":"ESMO Open"},{"key":"ref_9","first-page":"107","article-title":"Estrogen Receptor May Play Important Role in Gender Differences of Early-Onset Colorectal Cancer","volume":"25","author":"Wang","year":"2026","journal-title":"Clin. Color. Cancer"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"713","DOI":"10.1038\/s41575-019-0189-8","article-title":"Global burden of colorectal cancer: Emerging trends, risk factors and prevention strategies","volume":"16","author":"Keum","year":"2019","journal-title":"Nat. Rev. Gastroenterol. Hepatol."},{"key":"ref_11","first-page":"233","article-title":"Colorectal cancer statistics, 2023","volume":"73","author":"Siegel","year":"2023","journal-title":"CA Cancer J. Clin."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"2825","DOI":"10.1007\/s12094-024-03801-0","article-title":"Gender and sex differences in colorectal cancer screening, diagnosis and treatment","volume":"27","author":"Safont","year":"2025","journal-title":"Clin. Transl. Oncol."},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Wele, P., Wu, X., and Shi, H. (2022). Sex-Dependent Differences in Colorectal Cancer: With a Focus on Obesity. Cells, 11.","DOI":"10.3390\/cells11223688"},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Martinez, A., Grosclaude, P., Lamy, S., and Delpierre, C. (2024). The Influence of Sex and\/or Gender on the Occurrence of Colorectal Cancer in the General Population in Developed Countries: A Scoping Review. Int. J. Public Health, 69.","DOI":"10.3389\/ijph.2024.1606736"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"102834","DOI":"10.1016\/j.critrevonc.2019.102834","article-title":"Revisiting the impact of lifestyle on colorectal cancer risk in a gender perspective","volume":"145","author":"Conti","year":"2020","journal-title":"Crit. Rev. Oncol. Hematol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"183","DOI":"10.1136\/bmjnph-2022-000554","article-title":"Lifestyle predictors of colorectal cancer in European populations: A systematic review","volume":"7","author":"Mertens","year":"2024","journal-title":"BMJ Nutr. Prev. Health"},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Barna, R., Dema, A., Jurescu, A., V\u0103duva, A.O., L\u0103zureanu, D.-C., Vi\u021ba, O., Natar\u00e2\u0219, B., Hurmuz, I., Vidac, A., and T\u0103ban, S. (2025). The Relevance of Sex and Age as Non-Modifiable Risk Factors in Relation to Clinical-Pathological Parameters in Colorectal Cancer. Life, 15.","DOI":"10.3390\/life15020156"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"48","DOI":"10.1186\/s13293-024-00623-1","article-title":"Sexual dimorphism in colorectal cancer: Molecular mechanisms and treatment strategies","volume":"15","year":"2024","journal-title":"Biol. Sex Differ."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"333","DOI":"10.5946\/ce.2025.189","article-title":"Epidemiology of colonic adenoma and cancer","volume":"59","author":"Kim","year":"2026","journal-title":"Clin. Endosc."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"920","DOI":"10.1002\/ijc.32844","article-title":"Endogenous sex hormones and colorectal cancer survival among men and women","volume":"147","author":"Yang","year":"2020","journal-title":"Int. J. Cancer"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"331","DOI":"10.1093\/eurpub\/ckad029","article-title":"Sex variation in colorectal cancer mortality: Trends and implications for screening","volume":"33","author":"Clark","year":"2023","journal-title":"Eur. J. Public Health"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"955","DOI":"10.1016\/j.cgh.2020.02.026","article-title":"Differences in Incidence and Mortality Trends of Colorectal Cancer Worldwide Based on Sex, Age, and Anatomic Location","volume":"19","author":"Wong","year":"2021","journal-title":"Clin. Gastroenterol. Hepatol."},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Ra, H., Jeong, S., Lee, H., Chung, J.-W., Kim, K.O., Lee, W.-S., Kim, J., Kwon, K.A., and Kim, J.H. (2024). Clinicopathological Differences between Right and Left Colorectal Cancer by Sex. J. Clin. Med., 13.","DOI":"10.3390\/jcm13102810"},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Jurescu, A., Dema, A., T\u0103ban, S., Barna, R., V\u0103duva, A.O., Vi\u021ba, O., Cornea, R., L\u0103zureanu, D.-C., Mure\u0219an, A., and Cornianu, M. (2026). Clinicopathological Features of Right vs. Left Colorectal Carcinomas: Do the Differences Really Matter?. Life, 16.","DOI":"10.3390\/life16020242"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"e15","DOI":"10.3747\/co.24.3410","article-title":"Is there a sex effect in colon cancer? Disease characteristics, management, and outcomes in routine clinical practice","volume":"24","author":"Quirt","year":"2017","journal-title":"Curr. Oncol."},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Gies, A., Niedermaier, T., Alwers, E., Hielscher, T., Weigl, K., Heisser, T., Schrotz-King, P., Hoffmeister, M., and Brenner, H. (2021). Consistent Major Differences in Sex- and Age-Specific Diagnostic Performance among Nine Faecal Immunochemical Tests Used for Colorectal Cancer Screening. Cancers, 13.","DOI":"10.3390\/cancers13143574"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"92","DOI":"10.1177\/0969141318804843","article-title":"Gender-specific cut-offs in colorectal cancer screening with FIT: Increased compliance and equal positivity rate","volume":"26","author":"Blom","year":"2019","journal-title":"J. Med. Screen"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"93","DOI":"10.3892\/ol.2024.14839","article-title":"Transcription factors and hormone receptors: Sex-specific targets for cancer therapy (Review)","volume":"29","author":"Kim","year":"2025","journal-title":"Oncol. Lett."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"71","DOI":"10.1007\/s00423-019-01850-6","article-title":"Gender comparison of clinical, histopathological, therapeutic and outcome factors in 185,967 colon cancer patients","volume":"405","author":"Schmuck","year":"2020","journal-title":"Langenbeck\u2019s Arch. Surg."},{"key":"ref_30","doi-asserted-by":"crossref","unstructured":"Hases, L., Ibrahim, A., Chen, X., Liu, Y., Hartman, J., and Williams, C. (2021). The Importance of Sex in the Discovery of Colorectal Cancer Prognostic Biomarkers. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22031354"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"9433","DOI":"10.1073\/pnas.122612899","article-title":"Mutations in APC, Kirsten-ras, and p53\u2014Alternative genetic pathways to colorectal cancer","volume":"99","author":"Smith","year":"2002","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"1177","DOI":"10.1053\/j.gastro.2015.06.047","article-title":"Genetics and Genetic Biomarkers in Sporadic Colorectal Cancer","volume":"149","author":"Carethers","year":"2015","journal-title":"Gastroenterology"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"794","DOI":"10.1158\/1078-0432.CCR-17-1234","article-title":"Colorectal Cancer Consensus Molecular Subtypes Translated to Preclinical Models Uncover Potentially Targetable Cancer Cell Dependencies","volume":"24","author":"Sveen","year":"2018","journal-title":"Clin. Cancer Res."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"361","DOI":"10.1038\/s41575-019-0126-x","article-title":"Immunotherapy in colorectal cancer: Rationale, challenges and potential","volume":"16","author":"Ganesh","year":"2019","journal-title":"Nat. Rev. Gastroenterol. Hepatol."},{"key":"ref_35","doi-asserted-by":"crossref","unstructured":"Geddes, A.E., Ray, A.L., Nofchissey, R.A., Esmaeili, A., Saunders, A., Bender, D.E., Khan, M., Aravindan, S., Ahrendsen, J.T., and Li, M. (2022). An analysis of sexual dimorphism in the tumor microenvironment of colorectal cancer. Front. Oncol., 12.","DOI":"10.3389\/fonc.2022.986103"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"48","DOI":"10.5534\/wjmh.190009","article-title":"Sex Differences in Gut Microbiota","volume":"38","author":"Kim","year":"2020","journal-title":"World J. Men\u2019s Health"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"1637","DOI":"10.1007\/s00384-013-1715-8","article-title":"Descriptive profile of PIK3CA-mutated colorectal cancer in postmenopausal women","volume":"28","author":"Phipps","year":"2013","journal-title":"Int. J. Color. Dis."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"S575","DOI":"10.33549\/physiolres.933808","article-title":"Gender-dependent expression of leading and passenger strand of miR-21 and miR-16 in human colorectal cancer and adjacent colonic tissues","volume":"66","author":"Hasakova","year":"2017","journal-title":"Physiol. Res."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"pkaa089","DOI":"10.1093\/jncics\/pkaa089","article-title":"Risk Factors and Incidence of Colorectal Cancer According to Major Molecular Subtypes","volume":"5","author":"Wang","year":"2021","journal-title":"JNCI Cancer Spectr."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"98629","DOI":"10.3748\/wjg.v31.i5.98629","article-title":"Risk factors, prevention and screening of colorectal cancer: A rising problem","volume":"31","author":"Tsukanov","year":"2025","journal-title":"World J. Gastroenterol."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"1027","DOI":"10.1002\/ijc.32870","article-title":"Inflammatory potential of the diet and risk of colorectal cancer in the European Prospective Investigation into Cancer and Nutrition study","volume":"147","author":"Jakszyn","year":"2020","journal-title":"Int. J. Cancer"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"5167","DOI":"10.3748\/wjg.v21.i17.5167","article-title":"Sex- and gender-specific disparities in colorectal cancer risk","volume":"21","author":"Kim","year":"2015","journal-title":"World J. Gastroenterol."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"608","DOI":"10.1038\/bjc.2011.549","article-title":"Meat consumption and the risk of incident distal colon and rectal adenoma","volume":"106","author":"Ferrucci","year":"2012","journal-title":"Br. J. Cancer"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"703854","DOI":"10.1155\/2013\/703854","article-title":"Subsite-specific dietary risk factors for colorectal cancer: A review of cohort studies","volume":"2013","author":"Hjartaker","year":"2013","journal-title":"J. Oncol."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"109","DOI":"10.1002\/jso.27096","article-title":"Race, age, and sex differences on the influence of obesity on colorectal cancer sidedness and mortality: A national cross-sectional study","volume":"127","author":"Ulanja","year":"2023","journal-title":"J. Surg. Oncol."},{"key":"ref_46","doi-asserted-by":"crossref","unstructured":"Jin, X., Cai, C., Zhao, J., Huang, L., Jin, B., Jia, Y., and Lyu, B. (2023). Opportunistic colonoscopy in healthy individuals: A non-trivial risk of adenoma. PLoS ONE, 18.","DOI":"10.1371\/journal.pone.0283575"},{"key":"ref_47","doi-asserted-by":"crossref","unstructured":"Rio, P., Gasbarrini, A., Gambassi, G., and Cianci, R. (2024). Pollutants, microbiota and immune system: Frenemies within the gut. Front. Public Health, 12.","DOI":"10.3389\/fpubh.2024.1285186"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"477","DOI":"10.1136\/gutjnl-2024-332523","article-title":"Emerging role of environmental pollutants in inflammatory bowel disease risk, outcomes and underlying mechanisms","volume":"74","author":"Estevinho","year":"2025","journal-title":"Gut"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"115454","DOI":"10.1016\/j.envres.2023.115454","article-title":"Long-term exposure to traffic noise and risk of incident colon cancer: A pooled study of eleven Nordic cohorts","volume":"224","author":"Roswall","year":"2023","journal-title":"Environ. Res."},{"key":"ref_50","doi-asserted-by":"crossref","unstructured":"Chitapanarux, T., Traisathit, P., Srikummoon, P., Thongsak, N., Nakharutai, N., Thumronglaohapun, S., Supasri, T., Hemwan, P., and Chitapanarux, I. (2026). Time-varying exposure to ambient air pollution and mortality among colon cancer patients in northern Thailand: A 15-year retrospective cohort study. Front. Public Health, 14.","DOI":"10.3389\/fpubh.2026.1684020"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"101334","DOI":"10.1016\/j.lanplh.2025.101334","article-title":"Long-term exposure to PM2.5 constituents and incident cancer among Medicare beneficiaries in the USA: A national cohort study","volume":"9","author":"Feng","year":"2025","journal-title":"Lancet Planet. Health"},{"key":"ref_52","doi-asserted-by":"crossref","unstructured":"Sawicki, T., Ruszkowska, M., Danielewicz, A., Niedzwiedzka, E., Arlukowicz, T., and Przybylowicz, K.E. (2021). A Review of Colorectal Cancer in Terms of Epidemiology, Risk Factors, Development, Symptoms and Diagnosis. Cancers, 13.","DOI":"10.3390\/cancers13092025"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"123530","DOI":"10.1016\/j.envpol.2024.123530","article-title":"Exposure to pesticides and risk of colorectal cancer: A systematic review and meta-analysis","volume":"345","author":"Xie","year":"2024","journal-title":"Environ. Pollut."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"6082","DOI":"10.1021\/jf501397m","article-title":"Quantitative analysis of neonicotinoid insecticide residues in foods: Implication for dietary exposures","volume":"62","author":"Chen","year":"2014","journal-title":"J. Agric. Food Chem."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"123516","DOI":"10.1016\/j.envpol.2024.123516","article-title":"Urinary neonicotinoid concentrations and obesity: A cross-sectional study among Chinese adolescents","volume":"345","author":"Wu","year":"2024","journal-title":"Environ. Pollut."},{"key":"ref_56","doi-asserted-by":"crossref","unstructured":"Zanchi, G., Tammaro, A., Monteleone, V., Vari, R., Santangelo, C., Silecchia, G., Petrucciani, N., Manella, S., Silenzi, A., and Tait, S. (2026). Acetamiprid exerts sex-specific effects on adipose tissue of subjects with severe obesity. Front. Toxicol., 8.","DOI":"10.3389\/ftox.2026.1769863"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"102840","DOI":"10.1016\/j.canep.2025.102840","article-title":"The clinical relevance of microplastic exposure on colorectal cancer: A systematic review","volume":"97","author":"Ghoreshi","year":"2025","journal-title":"Cancer Epidemiol."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"12431","DOI":"10.3748\/wjg.v20.i35.12431","article-title":"Occupational exposures and colorectal cancers: A quantitative overview of epidemiological evidence","volume":"20","author":"Oddone","year":"2014","journal-title":"World J. Gastroenterol."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"865","DOI":"10.1001\/jamasurg.2021.2380","article-title":"Characteristics of Early-Onset vs Late-Onset Colorectal Cancer: A Review","volume":"156","author":"Collaborative","year":"2021","journal-title":"JAMA Surg."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"2397","DOI":"10.1007\/s00204-025-04025-z","article-title":"Mechanisms of bisphenol A and its analogs as endocrine disruptors via nuclear receptors and related signaling pathways","volume":"99","author":"Stanojevic","year":"2025","journal-title":"Arch. Toxicol."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"112662","DOI":"10.1016\/j.fct.2021.112662","article-title":"Effects of bisphenol A on the proliferation, migration, and tumor growth of colon cancer cells: In vitro and in vivo evaluation with mechanistic insights related to ERK and 5-HT3","volume":"158","author":"Jun","year":"2021","journal-title":"Food Chem. Toxicol."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"109182","DOI":"10.1016\/j.biopha.2019.109182","article-title":"Bisphenol A induces apoptosis, oxidative stress and inflammatory response in colon and liver of mice in a mitochondria-dependent manner","volume":"117","author":"Wang","year":"2019","journal-title":"Biomed. Pharmacother."},{"key":"ref_63","doi-asserted-by":"crossref","unstructured":"Li, Y., Lou, J., Hong, S., Hou, D., Lv, Y., Guo, Z., Wang, K., Xu, Y., Zhai, Y., and Liu, H. (2023). The role of heavy metals in the development of colorectal cancer. BMC Cancer, 23.","DOI":"10.1186\/s12885-023-11120-w"},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"18","DOI":"10.1007\/s40572-025-00482-x","article-title":"Current Understanding of Sex Differences in Metal-Induced Diseases","volume":"12","author":"Lu","year":"2025","journal-title":"Curr. Environ. Health Rep."},{"key":"ref_65","doi-asserted-by":"crossref","unstructured":"Bereshchenko, O., Bruscoli, S., and Riccardi, C. (2018). Glucocorticoids, Sex Hormones, and Immunity. Front. Immunol., 9.","DOI":"10.3389\/fimmu.2018.01332"},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"411","DOI":"10.1093\/humupd\/dmi008","article-title":"Sex hormones and the immune response in humans","volume":"11","author":"Bouman","year":"2005","journal-title":"Hum. Reprod. Updat."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"299","DOI":"10.1016\/j.mam.2006.07.001","article-title":"Structure-function relationship of estrogen receptor alpha and beta: Impact on human health","volume":"27","author":"Ascenzi","year":"2006","journal-title":"Mol. Asp. Med."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"106632","DOI":"10.1016\/j.jsbmb.2024.106632","article-title":"The role of estrogen receptors in intracellular estrogen signaling pathways, an overview","volume":"245","author":"Gui","year":"2025","journal-title":"J. Steroid Biochem. Mol. Biol."},{"key":"ref_69","doi-asserted-by":"crossref","unstructured":"Vona, R., Cittadini, C., Ortona, E., and Matarrese, P. (2025). Sex Disparity in Cancer: Role of Autophagy and Estrogen Receptors. Cells, 14.","DOI":"10.3390\/cells14040273"},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"4613","DOI":"10.1210\/endo.138.11.5496","article-title":"Tissue Distribution and Quantitative Analysis of Estrogen Receptor-\u03b1 (ER\u03b1) and Estrogen Receptor-\u03b2 (ER\u03b2) Messenger Ribonucleic Acid in the Wild-Type and ER\u03b1-Knockout Mouse","volume":"138","author":"Couse","year":"1997","journal-title":"Endocrinology"},{"key":"ref_71","doi-asserted-by":"crossref","unstructured":"Refaat, B., Aslam, A., Idris, S., Almalki, A.H., Alkhaldi, M.Y., Asiri, H.A., Almaimani, R.A., Mujalli, A., Minshawi, F., and Alamri, S.A. (2023). Profiling estrogen, progesterone, and androgen receptors in colorectal cancer in relation to gender, menopausal status, clinical stage, and tumour sidedness. Front. Endocrinol., 14.","DOI":"10.3389\/fendo.2023.1187259"},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"778","DOI":"10.1038\/nrd3551","article-title":"Development of subtype-selective oestrogen receptor-based therapeutics","volume":"10","author":"Nilsson","year":"2011","journal-title":"Nat. Rev. Drug Discov."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"361","DOI":"10.1016\/j.mce.2011.09.026","article-title":"Estrogen dependent signaling in reproductive tissues\u2014A role for estrogen receptors and estrogen related receptors","volume":"348","author":"Gibson","year":"2012","journal-title":"Mol. Cell. Endocrinol."},{"key":"ref_74","doi-asserted-by":"crossref","unstructured":"Gong, Z., Yang, S., Wei, M., Vlantis, A.C., Chan, J.Y.K., van Hasselt, C.A., Li, D., Zeng, X., Xue, L., and Tong, M.C.F. (2022). The Isoforms of Estrogen Receptor Alpha and Beta in Thyroid Cancer. Front. Oncol., 12.","DOI":"10.3389\/fonc.2022.916804"},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"335","DOI":"10.1146\/annurev.physiol.67.040403.120151","article-title":"Regulation of signal transduction pathways by estrogen and progesterone","volume":"67","author":"Edwards","year":"2005","journal-title":"Annu. Rev. Physiol."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"1535","DOI":"10.1152\/physrev.2001.81.4.1535","article-title":"Mechanisms of estrogen action","volume":"81","author":"Nilsson","year":"2001","journal-title":"Physiol. Rev."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"340","DOI":"10.1056\/NEJMra000471","article-title":"Production and Actions of Estrogens","volume":"346","author":"Tschugguel","year":"2002","journal-title":"N. Engl. J. Med."},{"key":"ref_78","doi-asserted-by":"crossref","unstructured":"Chen, P., Li, B., and Ou-Yang, L. (2022). Role of estrogen receptors in health and disease. Front. Endocrinol., 13.","DOI":"10.3389\/fendo.2022.839005"},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"477","DOI":"10.1016\/j.tem.2009.06.009","article-title":"Plasma membrane estrogen receptors","volume":"20","author":"Levin","year":"2009","journal-title":"Trends Endocrinol. Metab."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"e23870","DOI":"10.1016\/j.heliyon.2023.e23870","article-title":"Intra-tumor ROS amplification by melatonin interferes in the apoptosis-autophagy-inflammation-EMT collusion in the breast tumor microenvironment","volume":"10","author":"Das","year":"2024","journal-title":"Heliyon"},{"key":"ref_81","doi-asserted-by":"crossref","unstructured":"Topi, G., Ghatak, S., Satapathy, S.R., Ehrnstr\u00f6m, R., Lydrup, M.-L., and Sj\u00f6lander, A. (2022). Combined Estrogen Alpha and Beta Receptor Expression Has a Prognostic Significance for Colorectal Cancer Patients. Front. Med., 241.","DOI":"10.3389\/fmed.2022.739620"},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"154298","DOI":"10.1016\/j.prp.2022.154298","article-title":"Expression patterns and clinical significance of estrogen receptor in non-small cell lung cancer","volume":"241","author":"Castellanos","year":"2023","journal-title":"Pathol. Res. Pract."},{"key":"ref_83","doi-asserted-by":"crossref","unstructured":"Hsu, L.H., Chu, N.M., and Kao, S.H. (2017). Estrogen, Estrogen Receptor and Lung Cancer. Int. J. Mol. Sci., 18.","DOI":"10.3390\/ijms18081713"},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"898","DOI":"10.20892\/j.issn.2095-3941.2024.0224","article-title":"Intricate roles of estrogen and estrogen receptors in digestive system cancers: A systematic review","volume":"21","author":"Gan","year":"2024","journal-title":"Cancer Biol. Med."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"1427","DOI":"10.1097\/MS9.0000000000004261","article-title":"Sex steroid receptors in colorectal cancer: Implications for tumor progression, therapeutic opportunities, and sex-specific outcomes","volume":"88","author":"Beniwal","year":"2026","journal-title":"Ann. Med. Surg."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"5842","DOI":"10.1158\/1078-0432.CCR-13-0325","article-title":"Molecular pathways: Estrogen pathway in colorectal cancer","volume":"19","author":"Barzi","year":"2013","journal-title":"Clin. Cancer Res."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"22","DOI":"10.1186\/s13167-016-0071-5","article-title":"The role of testosterone in colorectal carcinoma: Pathomechanisms and open questions","volume":"7","author":"Roshan","year":"2016","journal-title":"EPMA J."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"325","DOI":"10.1002\/(SICI)1097-0215(20000501)86:3<325::AID-IJC4>3.0.CO;2-G","article-title":"Altered expression of androgen-receptor isoforms in human colon-cancer tissues","volume":"86","author":"Catalano","year":"2000","journal-title":"Int. J. Cancer"},{"key":"ref_89","doi-asserted-by":"crossref","unstructured":"Wenxuan, L., Liu, L., Zhang, L., Qiu, Z., Wu, Z., and Deng, W. (2023). Role of gonadally synthesized steroid hormones in the colorectal cancer microenvironment. Front. Oncol., 13.","DOI":"10.3389\/fonc.2023.1323826"},{"key":"ref_90","doi-asserted-by":"crossref","unstructured":"Abancens, M., Bustos, V., Harvey, H., McBryan, J., and Harvey, B.J. (2020). Sexual Dimorphism in Colon Cancer. Front. Oncol., 10.","DOI":"10.3389\/fonc.2020.607909"},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"1760","DOI":"10.1093\/jnci\/djq419","article-title":"Risk of colorectal cancer in men on long-term androgen deprivation therapy for prostate cancer","volume":"102","author":"Gillessen","year":"2010","journal-title":"J. Natl. Cancer Inst."},{"key":"ref_92","first-page":"949","article-title":"Risk of colorectal adenocarcinoma in men receiving androgen deprivation therapy for prostate cancer; a nationwide cohort study","volume":"34","author":"Shore","year":"2023","journal-title":"Cancer Causes Control."},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"196","DOI":"10.4143\/crt.2022.080","article-title":"Changes in Gut Microbiome upon Orchiectomy and Testosterone Administration in AOM\/DSS-Induced Colon Cancer Mouse Model","volume":"55","author":"Song","year":"2023","journal-title":"Cancer Res. Treat."},{"key":"ref_94","first-page":"3145","article-title":"Testosterone strongly enhances azoxymethane\/dextran sulfate sodium-induced colorectal cancer development in C57BL\/6 mice","volume":"11","author":"Song","year":"2021","journal-title":"Am. J. Cancer Res."},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"16514","DOI":"10.1073\/pnas.1323064111","article-title":"Sex disparity in colonic adenomagenesis involves promotion by male hormones, not protection by female hormones","volume":"111","author":"Heijmans","year":"2014","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"1033","DOI":"10.1002\/ijc.34116","article-title":"Circulating free testosterone and risk of aggressive prostate cancer: Prospective and Mendelian randomisation analyses in international consortia","volume":"151","author":"Watts","year":"2022","journal-title":"Int. J. Cancer"},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"2471","DOI":"10.31557\/APJCP.2019.20.8.2471","article-title":"Prognostic Significance of Cyclin D1 Over-expression in Colorectal Cancer: An Experience from Madinah, Saudi Arabia","volume":"20","author":"Albasri","year":"2019","journal-title":"Asian Pac. J. Cancer Prev."},{"key":"ref_98","doi-asserted-by":"crossref","unstructured":"Mahbub, A.A., Aslam, A., Elzubier, M.E., El-Boshy, M., Abdelghany, A.H., Ahmad, J., Idris, S., Almaimani, R., Alsaegh, A., and El-Readi, M.Z. (2022). Enhanced anti-cancer effects of oestrogen and progesterone co-therapy against colorectal cancer in males. Front. Endocrinol., 13.","DOI":"10.3389\/fendo.2022.941834"},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"217","DOI":"10.1530\/EC-18-0374","article-title":"Estradiol and progesterone regulate proliferation and apoptosis in colon cancer","volume":"8","author":"Sasso","year":"2019","journal-title":"Endocr. Connect."},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"164","DOI":"10.1111\/j.1524-4741.2007.00548.x","article-title":"Invasive Apocrine Carcinoma of the Breast: Clinicopathologic Features of 57 Patients","volume":"14","author":"Tanaka","year":"2008","journal-title":"Breast J."},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"95","DOI":"10.3892\/or.2021.8046","article-title":"Progesterone suppresses the progression of colonic carcinoma by increasing the activity of the GADD45\u03b1\/JNK\/c-Jun signalling pathway","volume":"45","author":"Zhang","year":"2021","journal-title":"Oncol. Rep."},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"117","DOI":"10.15430\/JCP.2018.23.3.117","article-title":"The Effect of Microbiota on Colon Carcinogenesis","volume":"23","author":"Yoon","year":"2018","journal-title":"J. Cancer Prev."},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"467","DOI":"10.1517\/14712598.2014.880420","article-title":"The human microbiome and bile acid metabolism: Dysbiosis, dysmetabolism, disease and intervention","volume":"14","author":"Jones","year":"2014","journal-title":"Expert Opin. Biol. Ther."},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"377","DOI":"10.1007\/978-3-642-38007-5_22","article-title":"Gut microbes, diet, and cancer","volume":"159","author":"Hullar","year":"2014","journal-title":"Cancer Treat. Res."},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"225","DOI":"10.1097\/PPO.0000000000000050","article-title":"Gut microbiome and colorectal adenomas","volume":"20","author":"Dulal","year":"2014","journal-title":"Cancer J."},{"key":"ref_106","doi-asserted-by":"crossref","unstructured":"Ma, M., Zheng, Z., Li, J., He, Y., Kang, W., and Ye, X. (2024). Association between the gut microbiota, inflammatory factors, and colorectal cancer: Evidence from Mendelian randomization analysis. Front. Microbiol., 15.","DOI":"10.3389\/fmicb.2024.1309111"},{"key":"ref_107","doi-asserted-by":"crossref","unstructured":"Xing, C., Du, Y., Duan, T., Nim, K., Chu, J., Wang, H.Y., and Wang, R.-F. (2022). Interaction between microbiota and immunity and its implication in colorectal cancer. Front. Immunol., 13.","DOI":"10.3389\/fimmu.2022.963819"},{"key":"ref_108","doi-asserted-by":"crossref","unstructured":"S\u00e1nchez-Alcoholado, L., Ord\u00f3\u00f1ez, R., Otero, A., Plaza-Andrade, I., Laborda-Illanes, A., Medina, J.A., Ramos-Molina, B., G\u00f3mez-Mill\u00e1n, J., and Queipo-Ortu\u00f1o, M.I. (2020). Gut Microbiota-Mediated Inflammation and Gut Permeability in Patients with Obesity and Colorectal Cancer. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21186782"},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"9","DOI":"10.21315\/mjms2020.27.4.2","article-title":"The Mechanism of Bacteroides fragilis Toxin Contributes to Colon Cancer Formation","volume":"27","author":"Cheng","year":"2020","journal-title":"Malays. J. Med. Sci."},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"102757","DOI":"10.1016\/j.anaerobe.2023.102757","article-title":"Comparison of microbiological profile of enterotoxigenic Bacteroides fragilis (ETBF) isolates from subjects with colorectal cancer (CRC) or intestinal pre-cancerous lesions versus healthy individuals and evaluation of environmental factors involved in intestinal dysbiosis","volume":"82","author":"Spigaglia","year":"2023","journal-title":"Anaerobe"},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"862","DOI":"10.1053\/j.gastro.2022.06.054","article-title":"Western-Style Diet, pks Island-Carrying Escherichia coli, and Colorectal Cancer: Analyses From Two Large Prospective Cohort Studies","volume":"163","author":"Arima","year":"2022","journal-title":"Gastroenterology"},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"105","DOI":"10.1177\/20533691251340491","article-title":"The gut microbiota in menopause: Is there a role for prebiotic and probiotic solutions?","volume":"31","author":"Liaquat","year":"2025","journal-title":"Post Reprod. Health"},{"key":"ref_113","doi-asserted-by":"crossref","unstructured":"Cong, X., Xu, W., Janton, S., Henderson, W.A., Matson, A., McGrath, J.M., Maas, K., and Graf, J. (2016). Gut Microbiome Developmental Patterns in Early Life of Preterm Infants: Impacts of Feeding and Gender. PLoS ONE, 11.","DOI":"10.1371\/journal.pone.0152751"},{"key":"ref_114","doi-asserted-by":"crossref","first-page":"23297","DOI":"10.1038\/s41598-021-02375-z","article-title":"Gut microbiota develop towards an adult profile in a sex-specific manner during puberty","volume":"11","author":"Korpela","year":"2021","journal-title":"Sci. Rep."},{"key":"ref_115","doi-asserted-by":"crossref","unstructured":"Flanagan, K.L., and Klein, S.L. (2026). Knowledge gaps and research priorities to understand sex differences in immunity. PLoS Biol., 24.","DOI":"10.1371\/journal.pbio.3003578"},{"key":"ref_116","doi-asserted-by":"crossref","first-page":"196","DOI":"10.1038\/s41467-025-66888-1","article-title":"Meta-analysis of 22,710 human microbiome metagenomes defines an oral-to-gut microbial enrichment score and associations with host health and disease","volume":"17","author":"Manghi","year":"2025","journal-title":"Nat. Commun."},{"key":"ref_117","doi-asserted-by":"crossref","first-page":"435","DOI":"10.1111\/jam.14943","article-title":"Gut microbiome is more stable in males than in females during the development of colorectal cancer","volume":"131","author":"Liao","year":"2021","journal-title":"J. Appl. Microbiol."},{"key":"ref_118","doi-asserted-by":"crossref","first-page":"106684","DOI":"10.1016\/j.micpath.2024.106684","article-title":"Third-generation PacBio sequencing to explore gut bacteria and gender in colorectal cancer","volume":"192","author":"Yu","year":"2024","journal-title":"Microb. Pathog."},{"key":"ref_119","doi-asserted-by":"crossref","first-page":"568","DOI":"10.1111\/apt.70252","article-title":"Systematic Review: The Relationship Between the Faecal Microbiome and Colorectal Neoplasia in Shotgun Metagenomic Studies","volume":"62","author":"Manning","year":"2025","journal-title":"Aliment. Pharmacol. Ther."},{"key":"ref_120","doi-asserted-by":"crossref","first-page":"192","DOI":"10.1016\/j.resmic.2019.03.003","article-title":"Serum level of sex steroid hormone is associated with diversity and profiles of human gut microbiome","volume":"170","author":"Shin","year":"2019","journal-title":"Res. Microbiol."},{"key":"ref_121","doi-asserted-by":"crossref","first-page":"E1182","DOI":"10.1152\/ajpendo.00338.2019","article-title":"The gut microbiota is a major regulator of androgen metabolism in intestinal contents","volume":"317","author":"Landin","year":"2019","journal-title":"Am. J. Physiol. Endocrinol. Metab."},{"key":"ref_122","doi-asserted-by":"crossref","first-page":"1332","DOI":"10.1016\/j.cell.2016.05.041","article-title":"From Dietary Fiber to Host Physiology: Short-Chain Fatty Acids as Key Bacterial Metabolites","volume":"165","author":"Koh","year":"2016","journal-title":"Cell"},{"key":"ref_123","doi-asserted-by":"crossref","first-page":"461","DOI":"10.1038\/s41575-019-0157-3","article-title":"The role of short-chain fatty acids in microbiota\u2013gut\u2013brain communication","volume":"16","author":"Dalile","year":"2019","journal-title":"Nat. Rev. Gastroenterol. Hepatol."},{"key":"ref_124","doi-asserted-by":"crossref","unstructured":"Parada Venegas, D., De la Fuente, M.K., Landskron, G., Gonz\u00e1lez, M.J., Quera, R., Dijkstra, G., Harmsen, H.J.M., Faber, K.N., and Hermoso, M.A. (2019). Short Chain Fatty Acids (SCFAs)-Mediated Gut Epithelial and Immune Regulation and Its Relevance for Inflammatory Bowel Diseases. Front. Immunol., 10, Erratum in Front. Immunol. 2019, 10, 1486. https:\/\/doi.org\/10.3389\/fimmu.2019.01486.","DOI":"10.3389\/fimmu.2019.01486"},{"key":"ref_125","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1016\/j.maturitas.2017.06.025","article-title":"Estrogen-gut microbiome axis: Physiological and clinical implications","volume":"103","author":"Baker","year":"2017","journal-title":"Maturitas"},{"key":"ref_126","doi-asserted-by":"crossref","first-page":"2425125","DOI":"10.1080\/2162402X.2024.2425125","article-title":"Estrogen-related differences in antitumor immunity and gut microbiome contribute to sexual dimorphism of colorectal cancer","volume":"13","author":"Lattanzi","year":"2024","journal-title":"Oncoimmunology"},{"key":"ref_127","doi-asserted-by":"crossref","unstructured":"Wu, Z., Sun, Y., Huang, W., Jin, Z., You, F., Li, X., and Xiao, C. (2024). Direct and indirect effects of estrogens, androgens and intestinal microbiota on colorectal cancer. Front. Cell. Infect. Microbiol., 14.","DOI":"10.3389\/fcimb.2024.1458033"},{"key":"ref_128","doi-asserted-by":"crossref","first-page":"12283","DOI":"10.1038\/s41598-020-69112-w","article-title":"17\u03b2-Estradiol supplementation changes gut microbiota diversity in intact and colorectal cancer-induced ICR male mice","volume":"10","author":"Song","year":"2020","journal-title":"Sci. Rep."},{"key":"ref_129","doi-asserted-by":"crossref","first-page":"2206238","DOI":"10.1002\/advs.202206238","article-title":"Male-Biased Gut Microbiome and Metabolites Aggravate Colorectal Cancer Development","volume":"10","author":"Wang","year":"2023","journal-title":"Adv. Sci."},{"key":"ref_130","doi-asserted-by":"crossref","first-page":"654","DOI":"10.5009\/gnl230385","article-title":"The Possible Preventative Role of Lactate- and Butyrate-Producing Bacteria in Colorectal Carcinogenesis","volume":"18","author":"Song","year":"2024","journal-title":"Gut Liver"},{"key":"ref_131","doi-asserted-by":"crossref","first-page":"1606","DOI":"10.1016\/j.csbj.2023.02.022","article-title":"Short-chain fatty acids reprogram metabolic profiles with the induction of reactive oxygen species production in human colorectal adenocarcinoma cells","volume":"21","author":"Huang","year":"2023","journal-title":"Comput. Struct. Biotechnol. J."},{"key":"ref_132","doi-asserted-by":"crossref","first-page":"1496","DOI":"10.1515\/cclm-2022-0583","article-title":"Strategies to minimise the current disadvantages experienced by women in faecal immunochemical test-based colorectal cancer screening","volume":"60","author":"Clark","year":"2022","journal-title":"Clin. Chem. Lab. Med."},{"key":"ref_133","doi-asserted-by":"crossref","first-page":"106692","DOI":"10.1016\/j.ypmed.2021.106692","article-title":"Contextual factors associated with cancer screening uptake: A systematic review of observational studies","volume":"150","author":"Rollet","year":"2021","journal-title":"Prev. Med."},{"key":"ref_134","doi-asserted-by":"crossref","first-page":"6497","DOI":"10.3748\/wjg.v28.i46.6497","article-title":"Nanotechnology for colorectal cancer detection and treatment","volume":"28","author":"Singh","year":"2022","journal-title":"World J. Gastroenterol."},{"key":"ref_135","doi-asserted-by":"crossref","first-page":"1291","DOI":"10.1016\/j.annonc.2020.06.022","article-title":"Localised colon cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up","volume":"31","author":"Tabernero","year":"2020","journal-title":"Ann. Oncol."},{"key":"ref_136","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1016\/j.annonc.2022.10.003","article-title":"Metastatic colorectal cancer: ESMO Clinical Practice Guideline for diagnosis, treatment and follow-up","volume":"34","author":"Committee","year":"2023","journal-title":"Ann. Oncol."},{"key":"ref_137","doi-asserted-by":"crossref","unstructured":"Cerrito, M.G., and Grassilli, E. (2021). Identifying Novel Actionable Targets in Colon Cancer. Biomedicines, 9.","DOI":"10.3390\/biomedicines9050579"},{"key":"ref_138","doi-asserted-by":"crossref","unstructured":"Adeleke, A., Adebayo, A.S., Agbaje, K., Olajubutu, O., and Adesina, S.K. (2025). Colorectal Cancer: Therapeutic Approaches and Their Complications. Biomedicines, 13.","DOI":"10.20944\/preprints202506.0111.v1"},{"key":"ref_139","doi-asserted-by":"crossref","first-page":"232","DOI":"10.1016\/j.critrevonc.2012.09.014","article-title":"Prospective of colon cancer treatments and scope for combinatorial approach to enhanced cancer cell apoptosis","volume":"86","author":"Mishra","year":"2013","journal-title":"Crit. Rev. Oncol. Hematol."},{"key":"ref_140","doi-asserted-by":"crossref","first-page":"102218","DOI":"10.1016\/j.ctrv.2021.102218","article-title":"Metastatic colorectal cancer: Advances in the folate-fluoropyrimidine chemotherapy backbone","volume":"98","author":"Glimelius","year":"2021","journal-title":"Cancer Treat. Rev."},{"key":"ref_141","doi-asserted-by":"crossref","first-page":"1656","DOI":"10.1093\/annonc\/mdl284","article-title":"Pharmacokinetic and demographic markers of 5-fluorouracil toxicity in 181 patients on adjuvant therapy for colorectal cancer","volume":"17","author":"Gusella","year":"2006","journal-title":"Ann. Oncol."},{"key":"ref_142","doi-asserted-by":"crossref","first-page":"100152","DOI":"10.1016\/j.crphar.2022.100152","article-title":"Sex differences in drug effects and\/or toxicity in oncology","volume":"4","author":"Rakshith","year":"2023","journal-title":"Curr. Res. Pharmacol. Drug Discov."},{"key":"ref_143","doi-asserted-by":"crossref","first-page":"361","DOI":"10.1007\/s00280-012-2018-4","article-title":"Gender-specific elimination of continuous-infusional 5-fluorouracil in patients with gastrointestinal malignancies: Results from a prospective population pharmacokinetic study","volume":"71","author":"Mueller","year":"2013","journal-title":"Cancer Chemother. Pharmacol."},{"key":"ref_144","doi-asserted-by":"crossref","first-page":"594","DOI":"10.1248\/bpb.b18-00707","article-title":"Sex-Dependent Adverse Drug Reactions to 5-Fluorouracil in Colorectal Cancer","volume":"42","author":"Lim","year":"2019","journal-title":"Biol. Pharm. Bull."},{"key":"ref_145","first-page":"110","article-title":"Impact of Sex on Chemotherapy Toxicity and Efficacy Among Patients With Metastatic Colorectal Cancer: Pooled Analysis of 5 Randomized Trials","volume":"18","year":"2019","journal-title":"Clin. Color. Cancer"},{"key":"ref_146","doi-asserted-by":"crossref","first-page":"400","DOI":"10.1093\/jnci\/djaa124","article-title":"Sex and Adverse Events of Adjuvant Chemotherapy in Colon Cancer: An Analysis of 34 640 Patients in the ACCENT Database","volume":"113","author":"Wagner","year":"2021","journal-title":"J. Natl. Cancer Inst."},{"key":"ref_147","doi-asserted-by":"crossref","first-page":"28463","DOI":"10.18632\/oncotarget.15307","article-title":"Expression of the cancer stem cell markers ABCG2 and OCT-4 in right-sided colon cancer predicts recurrence and poor outcomes","volume":"8","author":"Hu","year":"2017","journal-title":"Oncotarget"},{"key":"ref_148","doi-asserted-by":"crossref","first-page":"116694","DOI":"10.1016\/j.ejca.2026.116694","article-title":"Sex differences in efficacy and toxicity of first-line treatment of metastatic colorectal cancer: An analysis of 18,041 patients in the ARCAD CRC database","volume":"238","author":"Wagner","year":"2026","journal-title":"Eur. J. Cancer"},{"key":"ref_149","doi-asserted-by":"crossref","first-page":"100246","DOI":"10.1016\/j.esmoop.2021.100246","article-title":"Impact of age and gender on the efficacy and safety of upfront therapy with panitumumab plus FOLFOX followed by panitumumab-based maintenance: A pre-specified subgroup analysis of the Valentino study","volume":"6","author":"Raimondi","year":"2021","journal-title":"ESMO Open"},{"key":"ref_150","doi-asserted-by":"crossref","first-page":"1969","DOI":"10.1093\/annonc\/mdz403","article-title":"Impact of age and gender on the safety and efficacy of chemotherapy plus bevacizumab in metastatic colorectal cancer: A pooled analysis of TRIBE and TRIBE2 studies","volume":"30","author":"Marmorino","year":"2019","journal-title":"Ann. Oncol."},{"key":"ref_151","doi-asserted-by":"crossref","first-page":"22","DOI":"10.1038\/s41392-020-0116-z","article-title":"Comprehensive review of targeted therapy for colorectal cancer","volume":"5","author":"Xie","year":"2020","journal-title":"Signal Transduct. Target. Ther."},{"key":"ref_152","doi-asserted-by":"crossref","unstructured":"Szefler, B., and Czelen, P. (2023). Will the Interactions of Some Platinum (II)-Based Drugs with B-Vitamins Reduce Their Therapeutic Effect in Cancer Patients? Comparison of Chemotherapeutic Agents such as Cisplatin, Carboplatin and Oxaliplatin-A Review. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms24021548"},{"key":"ref_153","doi-asserted-by":"crossref","first-page":"1296","DOI":"10.1053\/j.gastro.2008.02.098","article-title":"Systemic treatment of colorectal cancer","volume":"134","author":"Wolpin","year":"2008","journal-title":"Gastroenterology"},{"key":"ref_154","doi-asserted-by":"crossref","first-page":"4779","DOI":"10.1200\/JCO.2007.11.3357","article-title":"Randomized, controlled trial of irinotecan plus infusional, bolus, or oral fluoropyrimidines in first-line treatment of metastatic colorectal cancer: Results from the BICC-C Study","volume":"25","author":"Fuchs","year":"2007","journal-title":"J. Clin. Oncol."},{"key":"ref_155","doi-asserted-by":"crossref","first-page":"3834","DOI":"10.3748\/wjg.v24.i34.3834","article-title":"Drug resistance and new therapies in colorectal cancer","volume":"24","author":"Xu","year":"2018","journal-title":"World J. Gastroenterol."},{"key":"ref_156","doi-asserted-by":"crossref","first-page":"1539","DOI":"10.1093\/annonc\/mdw206","article-title":"Randomized phase III study of bevacizumab plus FOLFIRI and bevacizumab plus mFOLFOX6 as first-line treatment for patients with metastatic colorectal cancer (WJOG4407G)","volume":"27","author":"Yamazaki","year":"2016","journal-title":"Ann. Oncol."},{"key":"ref_157","doi-asserted-by":"crossref","first-page":"162","DOI":"10.1016\/j.ejca.2022.10.022","article-title":"Evaluating sex as a predictive marker for response to bevacizumab in metastatic colorectal carcinoma: Pooled analysis of 3,369 patients in the ARCAD database","volume":"178","author":"Margalit","year":"2023","journal-title":"Eur. J. Cancer"},{"key":"ref_158","doi-asserted-by":"crossref","first-page":"240","DOI":"10.35772\/ghm.2020.01050","article-title":"Impact of sex and histology on the therapeutic effects of fluoropyrimidines and oxaliplatin plus bevacizumab for patients with metastatic colorectal cancer in the SOFT trial","volume":"2","author":"Yamada","year":"2020","journal-title":"Glob. Health Med."},{"key":"ref_159","doi-asserted-by":"crossref","first-page":"4664","DOI":"10.1158\/1078-0432.CCR-07-0065","article-title":"Panitumumab, a monoclonal anti epidermal growth factor receptor antibody in colorectal cancer: Another one or the one?","volume":"13","author":"Messersmith","year":"2007","journal-title":"Clin. Cancer Res."},{"key":"ref_160","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1177\/1758834015614530","article-title":"Pharmacologic resistance in colorectal cancer: A review","volume":"8","author":"Hammond","year":"2016","journal-title":"Ther. Adv. Med. Oncol."},{"key":"ref_161","doi-asserted-by":"crossref","first-page":"337","DOI":"10.1056\/NEJMoa033025","article-title":"Cetuximab monotherapy and cetuximab plus irinotecan in irinotecan-refractory metastatic colorectal cancer","volume":"351","author":"Cunningham","year":"2004","journal-title":"N. Engl. J. Med."},{"key":"ref_162","doi-asserted-by":"crossref","first-page":"1760","DOI":"10.1002\/ijc.34156","article-title":"Early onset metastatic colorectal cancer in patients receiving panitumumab-based upfront strategy: Overall and sex-specific outcomes in the Valentino trial","volume":"151","author":"Raimondi","year":"2022","journal-title":"Int. J. Cancer"},{"key":"ref_163","doi-asserted-by":"crossref","first-page":"101568","DOI":"10.1016\/j.esmoop.2023.101568","article-title":"Impact of sex on the efficacy and safety of panitumumab plus fluorouracil and folinic acid versus fluorouracil and folinic acid alone as maintenance therapy in RAS WT metastatic colorectal cancer (mCRC). Subgroup analysis of the PanaMa-study (AIO-KRK-0212)","volume":"8","author":"Heinrich","year":"2023","journal-title":"ESMO Open"},{"key":"ref_164","doi-asserted-by":"crossref","first-page":"64136","DOI":"10.18632\/oncotarget.11636","article-title":"Regorafenib (Stivarga) pharmacologically targets epithelial-mesenchymal transition in colorectal cancer","volume":"7","author":"Fan","year":"2016","journal-title":"Oncotarget"},{"key":"ref_165","doi-asserted-by":"crossref","first-page":"1966","DOI":"10.1038\/bjc.2015.160","article-title":"Combination of microsatellite instability and BRAF mutation status for subtyping colorectal cancer","volume":"112","author":"Seppala","year":"2015","journal-title":"Br. J. Cancer"},{"key":"ref_166","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1053\/j.seminoncol.2024.10.004","article-title":"Gender-based differences in the efficacy of anti-EGFR\/BRAF\/MEK targeted therapy in patients with BRAF-mutated metastatic colorectal cancer","volume":"52","author":"Pala","year":"2025","journal-title":"Semin. Oncol."},{"key":"ref_167","doi-asserted-by":"crossref","first-page":"1632","DOI":"10.1056\/NEJMoa1908075","article-title":"Encorafenib, Binimetinib, and Cetuximab in BRAF V600E-Mutated Colorectal Cancer","volume":"381","author":"Kopetz","year":"2019","journal-title":"N. Engl. J. Med."},{"key":"ref_168","first-page":"59","article-title":"Adverse Events Associated with Encorafenib Plus Cetuximab in Patients with BRAFV600E-mutant Metastatic Colorectal Cancer: An in-depth Analysis of the BEACON CRC Study","volume":"22","author":"Taieb","year":"2023","journal-title":"Clin. Color. Cancer"},{"key":"ref_169","doi-asserted-by":"crossref","first-page":"103696","DOI":"10.1016\/j.esmoop.2024.103696","article-title":"Efficacy and safety of the combination of encorafenib\/cetuximab with or without binimetinib in patients with BRAF V600E-mutated metastatic colorectal cancer: An AGEO real-world multicenter study","volume":"9","author":"Gallois","year":"2024","journal-title":"ESMO Open"},{"key":"ref_170","doi-asserted-by":"crossref","first-page":"2996","DOI":"10.1002\/ijc.33056","article-title":"Revolutionizing the landscape of colorectal cancer treatment: The potential role of immune checkpoint inhibitors","volume":"147","author":"Tolba","year":"2020","journal-title":"Int. J. Cancer"},{"key":"ref_171","doi-asserted-by":"crossref","first-page":"3837","DOI":"10.7150\/ijbs.64077","article-title":"Immunotherapy in colorectal cancer: Current achievements and future perspective","volume":"17","author":"Fan","year":"2021","journal-title":"Int. J. Biol. Sci."},{"key":"ref_172","doi-asserted-by":"crossref","first-page":"2509","DOI":"10.1056\/NEJMoa1500596","article-title":"PD-1 Blockade in Tumors with Mismatch-Repair Deficiency","volume":"372","author":"Le","year":"2015","journal-title":"N. Engl. J. Med."},{"key":"ref_173","doi-asserted-by":"crossref","first-page":"1779","DOI":"10.1038\/s41467-020-15679-x","article-title":"Sex-associated molecular differences for cancer immunotherapy","volume":"11","author":"Ye","year":"2020","journal-title":"Nat. Commun."},{"key":"ref_174","doi-asserted-by":"crossref","first-page":"105028","DOI":"10.1016\/j.phrs.2020.105028","article-title":"Age, sex, and specific gene mutations affect the effects of immune checkpoint inhibitors in colorectal cancer","volume":"159","author":"Lin","year":"2020","journal-title":"Pharmacol. Res."},{"key":"ref_175","doi-asserted-by":"crossref","first-page":"1474","DOI":"10.1200\/JCO.21.02377","article-title":"Sex Differences in Risk of Severe Adverse Events in Patients Receiving Immunotherapy, Targeted Therapy, or Chemotherapy in Cancer Clinical Trials","volume":"40","author":"Unger","year":"2022","journal-title":"J. Clin. Oncol."}],"container-title":["Cells"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2073-4409\/15\/11\/1039\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,6,9]],"date-time":"2026-06-09T04:15:40Z","timestamp":1780978540000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2073-4409\/15\/11\/1039"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,6,5]]},"references-count":175,"journal-issue":{"issue":"11","published-online":{"date-parts":[[2026,6]]}},"alternative-id":["cells15111039"],"URL":"https:\/\/doi.org\/10.3390\/cells15111039","relation":{},"ISSN":["2073-4409"],"issn-type":[{"value":"2073-4409","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,6,5]]}}}