{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,11]],"date-time":"2026-09-11T15:38:03Z","timestamp":1789141083551,"version":"build-2803163510"},"reference-count":72,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2026,2,14]],"date-time":"2026-02-14T00:00:00Z","timestamp":1771027200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0"},{"start":{"date-parts":[[2026,3,16]],"date-time":"2026-03-16T00:00:00Z","timestamp":1773619200000},"content-version":"vor","delay-in-days":30,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0"}],"funder":[{"name":"the CAMS Innovation Fund for Medical Sciences","award":["2021-I2M-2-004"],"award-info":[{"award-number":["2021-I2M-2-004"]}]},{"name":"Yunnan Province Xingdian Talent Support Program","award":["XDYC-CYCX-2023-0074"],"award-info":[{"award-number":["XDYC-CYCX-2023-0074"]}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Sci Rep"],"DOI":"10.1038\/s41598-026-38712-3","type":"journal-article","created":{"date-parts":[[2026,2,14]],"date-time":"2026-02-14T04:18:51Z","timestamp":1771042731000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Association of EGFR and EGF gene polymorphisms with cervical cancer in a case\u2013control study and cross-cancer meta-analysis"],"prefix":"10.1038","volume":"16","author":[{"given":"Yuhan","family":"Shi","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yueting","family":"Yao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fengquan","family":"He","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xueya","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jinmei","family":"Xu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhiling","family":"Yan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Li","family":"Shi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yufeng","family":"Yao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,2,14]]},"reference":[{"key":"38712_CR1","doi-asserted-by":"publisher","first-page":"e197","DOI":"10.1016\/s2214-109x(22)00501-0","volume":"11","author":"D Singh","year":"2023","unstructured":"Singh, D. et al. Global estimates of incidence and mortality of cervical cancer in 2020: A baseline analysis of the WHO Global Cervical Cancer Elimination Initiative. Lancet Glob Health 11, e197\u2013e206. https:\/\/doi.org\/10.1016\/s2214-109x(22)00501-0 (2023).","journal-title":"Lancet Glob Health"},{"key":"38712_CR2","doi-asserted-by":"publisher","first-page":"1067","DOI":"10.46234\/ccdcw2022.215","volume":"4","author":"L Wang","year":"2022","unstructured":"Wang, L. Accelerating cervical cancer prevention and control in China to achieve cervical cancer elimination strategy objectives. China CDC Wkly. 4, 1067\u20131069. https:\/\/doi.org\/10.46234\/ccdcw2022.215 (2022).","journal-title":"China CDC Wkly."},{"key":"38712_CR3","doi-asserted-by":"publisher","first-page":"720","DOI":"10.21147\/j.issn.1000-9604.2020.06.05","volume":"32","author":"S Zhang","year":"2020","unstructured":"Zhang, S., Xu, H., Zhang, L. & Qiao, Y. Cervical cancer: Epidemiology, risk factors and screening. Chin J. Cancer Res. 32, 720\u2013728. https:\/\/doi.org\/10.21147\/j.issn.1000-9604.2020.06.05 (2020).","journal-title":"Chin J. Cancer Res."},{"key":"38712_CR4","doi-asserted-by":"publisher","first-page":"8089","DOI":"10.3390\/ijerph17218089","volume":"17","author":"A Mbemi","year":"2020","unstructured":"Mbemi, A., Khanna, S., Njiki, S., Yedjou, C. G. & Tchounwou, P. B. Impact of gene-environment interactions on cancer development. Int. J. Environ. Res. Public Health 17, 8089. https:\/\/doi.org\/10.3390\/ijerph17218089 (2020).","journal-title":"Int. J. Environ. Res. Public Health"},{"key":"38712_CR5","doi-asserted-by":"publisher","first-page":"229","DOI":"10.1016\/S0168-1702(02)00191-0","volume":"89","author":"A Hildesheim","year":"2002","unstructured":"Hildesheim, A. & Wang, S. S. Host and viral genetics and risk of cervical cancer: A review. Virus Res. 89, 229\u2013240. https:\/\/doi.org\/10.1016\/S0168-1702(02)00191-0 (2002).","journal-title":"Virus Res."},{"key":"38712_CR6","doi-asserted-by":"publisher","first-page":"79","DOI":"10.1375\/twin.15.1.79","volume":"15","author":"EE Moore","year":"2012","unstructured":"Moore, E. E., Wark, J. D., Hopper, J. L., Erbas, B. & Garland, S. M. The roles of genetic and environmental factors on risk of cervical cancer: A review of classical twin studies. Twin Res. Hum. Genet. 15, 79\u201386. https:\/\/doi.org\/10.1375\/twin.15.1.79 (2012).","journal-title":"Twin Res. Hum. Genet."},{"key":"38712_CR7","doi-asserted-by":"publisher","first-page":"698","DOI":"10.1002\/1097-0215(20001201)88:5<698::aid-ijc3>3.0.co;2-j","volume":"88","author":"PK Magnusson","year":"2000","unstructured":"Magnusson, P. K., Lichtenstein, P. & Gyllensten, U. B. Heritability of cervical tumours. Int. J. Cancer 88, 698\u2013701. https:\/\/doi.org\/10.1002\/1097-0215(20001201)88:5%3c698::aid-ijc3%3e3.0.co;2-j (2000).","journal-title":"Int. J. Cancer"},{"key":"38712_CR8","doi-asserted-by":"publisher","first-page":"548","DOI":"10.1016\/s1470-2045(21)00028-0","volume":"22","author":"SJ Bowden","year":"2021","unstructured":"Bowden, S. J. et al. Genetic variation in cervical preinvasive and invasive disease: A genome-wide association study. Lancet Oncol. 22, 548\u2013557. https:\/\/doi.org\/10.1016\/s1470-2045(21)00028-0 (2021).","journal-title":"Lancet Oncol."},{"key":"38712_CR9","doi-asserted-by":"publisher","first-page":"2748","DOI":"10.3390\/cancers13112748","volume":"13","author":"ML Uribe","year":"2021","unstructured":"Uribe, M. L., Marrocco, I. & Yarden, Y. EGFR in cancer: Signaling mechanisms, drugs, and acquired resistance. Cancers (Basel) 13, 2748. https:\/\/doi.org\/10.3390\/cancers13112748 (2021).","journal-title":"Cancers (Basel)"},{"key":"38712_CR10","doi-asserted-by":"publisher","first-page":"147","DOI":"10.1016\/j.cytogfr.2004.01.004","volume":"15","author":"RW Wong","year":"2004","unstructured":"Wong, R. W. & Guillaud, L. The role of epidermal growth factor and its receptors in mammalian CNS. Cytokine Growth Factor Rev. 15, 147\u2013156. https:\/\/doi.org\/10.1016\/j.cytogfr.2004.01.004 (2004).","journal-title":"Cytokine Growth Factor Rev."},{"key":"38712_CR11","doi-asserted-by":"publisher","first-page":"170","DOI":"10.1038\/ncponc0476","volume":"3","author":"JE Dowell","year":"2006","unstructured":"Dowell, J. E. & Minna, J. D. EGFR mutations and molecularly targeted therapy: A new era in the treatment of lung cancer. Nat. Clin. Pract. Oncol. 3, 170\u2013171. https:\/\/doi.org\/10.1038\/ncponc0476 (2006).","journal-title":"Nat. Clin. Pract. Oncol."},{"key":"38712_CR12","first-page":"4423","volume":"26","author":"S Lev-Ari","year":"2006","unstructured":"Lev-Ari, S. et al. Inhibition of pancreatic and lung adenocarcinoma cell survival by curcumin is associated with increased apoptosis, down-regulation of COX-2 and EGFR and inhibition of Erk1\/2 activity. Anticancer Res. 26, 4423\u20134430 (2006).","journal-title":"Anticancer Res."},{"key":"38712_CR13","doi-asserted-by":"publisher","first-page":"1469","DOI":"10.1002\/2211-5463.13653","volume":"13","author":"R Kobayashi","year":"2023","unstructured":"Kobayashi, R. et al. The EGF\/EGFR axis and its downstream signaling pathways regulate the motility and proliferation of cultured oral keratinocytes. FEBS Open Bio 13, 1469\u20131484. https:\/\/doi.org\/10.1002\/2211-5463.13653 (2023).","journal-title":"FEBS Open Bio"},{"key":"38712_CR14","doi-asserted-by":"publisher","first-page":"52","DOI":"10.3390\/cancers9050052","volume":"9","author":"P Wee","year":"2017","unstructured":"Wee, P. & Wang, Z. Epidermal growth factor receptor cell proliferation signaling pathways. Cancers 9, 52 (2017).","journal-title":"Cancers"},{"key":"38712_CR15","doi-asserted-by":"publisher","DOI":"10.1590\/1414-431x202010754","volume":"54","author":"FG Gomes","year":"2021","unstructured":"Gomes, F. G. et al. Epidermal growth factor receptor regulates fibrinolytic pathway elements in cervical cancer: Functional and prognostic implications. Braz. J. Med. Biol. Res. 54, e10754. https:\/\/doi.org\/10.1590\/1414-431x202010754 (2021).","journal-title":"Braz. J. Med. Biol. Res."},{"key":"38712_CR16","doi-asserted-by":"publisher","first-page":"179","DOI":"10.1016\/j.ijbiomac.2021.11.117","volume":"194","author":"S Muthusami","year":"2022","unstructured":"Muthusami, S., Sabanayagam, R., Periyasamy, L., Muruganantham, B. & Park, W. Y. A review on the role of epidermal growth factor signaling in the development, progression and treatment of cervical cancer. Int. J. Biol. Macromol. 194, 179\u2013187. https:\/\/doi.org\/10.1016\/j.ijbiomac.2021.11.117 (2022).","journal-title":"Int. J. Biol. Macromol."},{"key":"38712_CR17","doi-asserted-by":"publisher","first-page":"720","DOI":"10.1038\/modpathol.2010.239","volume":"24","author":"M Schrevel","year":"2011","unstructured":"Schrevel, M. et al. Molecular mechanisms of epidermal growth factor receptor overexpression in patients with cervical cancer. Mod. Pathol. 24, 720\u2013728. https:\/\/doi.org\/10.1038\/modpathol.2010.239 (2011).","journal-title":"Mod. Pathol."},{"key":"38712_CR18","doi-asserted-by":"publisher","first-page":"11653","DOI":"10.1007\/s11033-022-07933-w","volume":"49","author":"ZK Lawi","year":"2022","unstructured":"Lawi, Z. K., Al-Shuhaib, M. B. S., Amara, I. B. & Alkhammas, A. H. Two missense variants of the epidermal growth factor receptor gene are associated with non small cell lung carcinoma in the subjects from Iraq. Mol. Biol. Rep. 49, 11653\u201311661. https:\/\/doi.org\/10.1007\/s11033-022-07933-w (2022).","journal-title":"Mol. Biol. Rep."},{"key":"38712_CR19","doi-asserted-by":"publisher","DOI":"10.1017\/s0016672314000032","author":"JG Carneiro","year":"2014","unstructured":"Carneiro, J. G. et al. Spectrum of somatic EGFR, KRAS, BRAF, PTEN mutations and TTF-1 expression in Brazilian lung cancer patients. Genet. Res. (Camb) https:\/\/doi.org\/10.1017\/s0016672314000032 (2014).","journal-title":"Genet. Res. (Camb)"},{"key":"38712_CR20","doi-asserted-by":"publisher","first-page":"53","DOI":"10.3390\/biom8030053","volume":"8","author":"NA Bashir","year":"2018","unstructured":"Bashir, N. A. et al. The association between epidermal growth factor receptor (EGFR) gene polymorphisms and lung cancer risk. Biomolecules 8, 53. https:\/\/doi.org\/10.3390\/biom8030053 (2018).","journal-title":"Biomolecules"},{"key":"38712_CR21","doi-asserted-by":"publisher","first-page":"199","DOI":"10.1186\/1471-2407-7-199","volume":"7","author":"JE Choi","year":"2007","unstructured":"Choi, J. E. et al. Polymorphisms in the epidermal growth factor receptor gene and the risk of primary lung cancer: A case-control study. BMC Cancer 7, 199. https:\/\/doi.org\/10.1186\/1471-2407-7-199 (2007).","journal-title":"BMC Cancer"},{"key":"38712_CR22","doi-asserted-by":"publisher","first-page":"2417","DOI":"10.1007\/s11033-019-04702-0","volume":"46","author":"AC Laus","year":"2019","unstructured":"Laus, A. C. et al. EGF+61 A>G polymorphism is not associated with lung cancer risk in the Brazilian population. Mol. Biol. Rep. 46, 2417\u20132425. https:\/\/doi.org\/10.1007\/s11033-019-04702-0 (2019).","journal-title":"Mol. Biol. Rep."},{"key":"38712_CR23","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0059254","volume":"8","author":"J Zhang","year":"2013","unstructured":"Zhang, J. et al. Association among polymorphisms in EGFR gene exons, lifestyle and risk of gastric cancer with gender differences in Chinese Han subjects. PLoS ONE 8, e59254. https:\/\/doi.org\/10.1371\/journal.pone.0059254 (2013).","journal-title":"PLoS ONE"},{"key":"38712_CR24","first-page":"150","volume":"65","author":"JH Torres-Jasso","year":"2013","unstructured":"Torres-Jasso, J. H. et al. Analysis of the polymorphisms EGFR-r521K and ERBB2-I655V in Mexican patients with gastric cancer and premalignant gastric lesions. Rev. Invest. Clin. 65, 150\u2013155 (2013).","journal-title":"Rev. Invest. Clin."},{"key":"38712_CR25","doi-asserted-by":"publisher","first-page":"631","DOI":"10.3892\/ol.2012.1041","volume":"5","author":"Z Zhan","year":"2013","unstructured":"Zhan, Z. et al. Functional epidermal growth factor gene polymorphisms and risk of gastric cancer. Oncol. Lett. 5, 631\u2013636. https:\/\/doi.org\/10.3892\/ol.2012.1041 (2013).","journal-title":"Oncol. Lett."},{"key":"38712_CR26","doi-asserted-by":"publisher","first-page":"202","DOI":"10.4103\/1947-2714.109189","volume":"5","author":"OH Mustafa","year":"2013","unstructured":"Mustafa, O. H. et al. Allele frequencies of the epidermal growth factor receptors polymorphism R521K in colorectal cancer patients and healthy subjects indicate a risk-reducing effect of K521 in Syrian population. N. Am. J. Med. Sci. 5, 202\u2013206. https:\/\/doi.org\/10.4103\/1947-2714.109189 (2013).","journal-title":"N. Am. J. Med. Sci."},{"key":"38712_CR27","first-page":"300","volume":"2","author":"EM Poole","year":"2011","unstructured":"Poole, E. M. et al. Genetic variability in EGFR, Src and HER2 and risk of colorectal adenoma and cancer. Int. J. Mol. Epidemiol. Genet. 2, 300\u2013315 (2011).","journal-title":"Int. J. Mol. Epidemiol. Genet."},{"key":"38712_CR28","doi-asserted-by":"publisher","first-page":"138","DOI":"10.5114\/ceh.2023.128131","volume":"9","author":"EA Gawish","year":"2023","unstructured":"Gawish, E. A., Abdelsameea, E., Osheba, I. S., Mohsen, Y. & El-Abd, M. G. Epidermal growth factor rs4444903 polymorphism and risk of cholangiocarcinoma. A case control study. Clin. Exp. Hepatol. 9, 138\u2013145. https:\/\/doi.org\/10.5114\/ceh.2023.128131 (2023).","journal-title":"Clin. Exp. Hepatol."},{"key":"38712_CR29","first-page":"2009","volume":"35","author":"PCM Vieira","year":"2015","unstructured":"Vieira, P. C. M. et al. Population stratification effect on cancer susceptibility in an admixed population from Brazilian Amazon. Anticancer Res. 35, 2009\u20132014 (2015).","journal-title":"Anticancer Res."},{"key":"38712_CR30","unstructured":"Chang, C.-P. Z. Glycemic Index, Glycemic Load, Genetic Susceptibility and Their Interactions with Lung and Upper Aerodigestive Tract Cancers. (University of California, 2018)."},{"key":"38712_CR31","first-page":"697","volume":"3","author":"M Elbendary","year":"2015","unstructured":"Elbendary, M. et al. Epidermal growth factor genetic polymorphism and its circulating serum level predict the risk of hepatocellular carcinoma in egyptian patients with hcv (genotype-4)-related cirrhosis. Int. J. Adv. Res. 3, 697\u2013705 (2015).","journal-title":"Int. J. Adv. Res."},{"key":"38712_CR32","doi-asserted-by":"publisher","first-page":"595","DOI":"10.1089\/gtmb.2013.0031","volume":"17","author":"J Wu","year":"2013","unstructured":"Wu, J. et al. Association of epidermal growth factor and epidermal growth factor receptor polymorphisms with the risk of hepatitis B virus-related hepatocellular carcinoma in the population of North China. Genet. Test Mol. Biomark. 17, 595\u2013600. https:\/\/doi.org\/10.1089\/gtmb.2013.0031 (2013).","journal-title":"Genet. Test Mol. Biomark."},{"key":"38712_CR33","doi-asserted-by":"publisher","first-page":"202","DOI":"10.1007\/s00018-023-04850-4","volume":"80","author":"C Tito","year":"2023","unstructured":"Tito, C. et al. Sorcin promotes migration in cancer and regulates the EGF-dependent EGFR signaling pathways. Cell Mol. Life Sci. 80, 202. https:\/\/doi.org\/10.1007\/s00018-023-04850-4 (2023).","journal-title":"Cell Mol. Life Sci."},{"key":"38712_CR34","doi-asserted-by":"publisher","first-page":"134","DOI":"10.1186\/s12935-014-0134-4","volume":"14","author":"Q Peng","year":"2014","unstructured":"Peng, Q. et al. EGF +61A\/G polymorphism contributes to increased gastric cancer risk: Evidence from a meta-analysis. Cancer Cell Int. 14, 134. https:\/\/doi.org\/10.1186\/s12935-014-0134-4 (2014).","journal-title":"Cancer Cell Int."},{"key":"38712_CR35","doi-asserted-by":"publisher","first-page":"D877","DOI":"10.1093\/nar\/gkv1340","volume":"44","author":"LD Ward","year":"2016","unstructured":"Ward, L. D. & Kellis, M. HaploReg v4: Systematic mining of putative causal variants, cell types, regulators and target genes for human complex traits and disease. Nucleic Acids Res. 44, D877-881. https:\/\/doi.org\/10.1093\/nar\/gkv1340 (2016).","journal-title":"Nucleic Acids Res."},{"key":"38712_CR36","doi-asserted-by":"publisher","first-page":"397","DOI":"10.1016\/s0140-6736(02)07600-6","volume":"359","author":"M Shahbazi","year":"2002","unstructured":"Shahbazi, M. et al. Association between functional polymorphism in EGF gene and malignant melanoma. Lancet 359, 397\u2013401. https:\/\/doi.org\/10.1016\/s0140-6736(02)07600-6 (2002).","journal-title":"Lancet"},{"key":"38712_CR37","doi-asserted-by":"publisher","first-page":"BS20190495","DOI":"10.1042\/bsr20190495","volume":"39","author":"X Zhu","year":"2019","unstructured":"Zhu, X., Shen, Y. & Xie, Q. The association between EGF A61G polymorphism and risk of colorectal cancer in a Chinese population: A case-control study. Biosci Rep 39, BS20190495. https:\/\/doi.org\/10.1042\/bsr20190495 (2019).","journal-title":"Biosci Rep"},{"key":"38712_CR38","doi-asserted-by":"publisher","first-page":"236","DOI":"10.1038\/jhg.2010.12","volume":"55","author":"J Zhu","year":"2010","unstructured":"Zhu, J. et al. A functional epidermal growth factor (EGF) polymorphism, EGF serum levels and renal cell carcinoma risk in a Chinese population. J. Hum. Genet. 55, 236\u2013240. https:\/\/doi.org\/10.1038\/jhg.2010.12 (2010).","journal-title":"J. Hum. Genet."},{"key":"38712_CR39","doi-asserted-by":"publisher","first-page":"321","DOI":"10.1007\/s10549-007-9784-4","volume":"111","author":"Y Wang","year":"2008","unstructured":"Wang, Y. et al. EGF promoter SNPs, plasma EGF levels and risk of breast cancer in Chinese women. Breast Cancer Res. Treat. 111, 321\u2013327. https:\/\/doi.org\/10.1007\/s10549-007-9784-4 (2008).","journal-title":"Breast Cancer Res. Treat."},{"key":"38712_CR40","doi-asserted-by":"publisher","first-page":"902","DOI":"10.1111\/j.1440-1843.2007.01152.x","volume":"12","author":"HG Kang","year":"2007","unstructured":"Kang, H. G. et al. +61A>G polymorphism in the EGF gene does not increase the risk of lung cancer. Respirology 12, 902\u2013905. https:\/\/doi.org\/10.1111\/j.1440-1843.2007.01152.x (2007).","journal-title":"Respirology"},{"key":"38712_CR41","first-page":"129","volume":"6","author":"V Chaleshi","year":"2013","unstructured":"Chaleshi, V. et al. The effect of 5\u2019untranslated region polymorphism in EGF gene, rs4444903, on colorectal cancer. Gastroenterol. Hepatol. Bed Bench 6, 129\u2013135 (2013).","journal-title":"Gastroenterol. Hepatol. Bed Bench"},{"key":"38712_CR42","doi-asserted-by":"publisher","unstructured":"The Genotype-Tissue Expression (GTEx) project. Nat. Genet. 45, 580\u2013585 (2013). https:\/\/doi.org\/10.1038\/ng.2653","DOI":"10.1038\/ng.2653"},{"key":"38712_CR43","doi-asserted-by":"publisher","first-page":"100","DOI":"10.1038\/nature10868","volume":"483","author":"A Prahallad","year":"2012","unstructured":"Prahallad, A. et al. Unresponsiveness of colon cancer to BRAF(V600E) inhibition through feedback activation of EGFR. Nature 483, 100\u2013103. https:\/\/doi.org\/10.1038\/nature10868 (2012).","journal-title":"Nature"},{"key":"38712_CR44","doi-asserted-by":"publisher","first-page":"82","DOI":"10.1038\/s41586-020-1969-6","volume":"578","author":"LA Aaltonen","year":"2020","unstructured":"Aaltonen, L. A. et al. Pan-cancer analysis of whole genomes. Nature 578, 82\u201393. https:\/\/doi.org\/10.1038\/s41586-020-1969-6 (2020).","journal-title":"Nature"},{"key":"38712_CR45","doi-asserted-by":"publisher","first-page":"321","DOI":"10.1016\/j.cell.2018.03.035","volume":"173","author":"F Sanchez-Vega","year":"2018","unstructured":"Sanchez-Vega, F. et al. Oncogenic signaling pathways in the cancer genome atlas. Cell 173, 321-337.e310. https:\/\/doi.org\/10.1016\/j.cell.2018.03.035 (2018).","journal-title":"Cell"},{"key":"38712_CR46","doi-asserted-by":"publisher","first-page":"4274","DOI":"10.1038\/s41467-019-12131-7","volume":"10","author":"G Fang","year":"2019","unstructured":"Fang, G. et al. Discovering genetic interactions bridging pathways in genome-wide association studies. Nat. Commun. 10, 4274. https:\/\/doi.org\/10.1038\/s41467-019-12131-7 (2019).","journal-title":"Nat. Commun."},{"key":"38712_CR47","doi-asserted-by":"publisher","first-page":"W444","DOI":"10.1093\/nar\/gkr321","volume":"39","author":"T Curk","year":"2011","unstructured":"Curk, T., Rot, G. & Zupan, B. SNPsyn: Detection and exploration of SNP\u2013SNP interactions. Nucleic Acids Res. 39, W444\u2013W449. https:\/\/doi.org\/10.1093\/nar\/gkr321 (2011).","journal-title":"Nucleic Acids Res."},{"key":"38712_CR48","doi-asserted-by":"publisher","unstructured":"The GTEx Consortium atlas of genetic regulatory effects across human tissues. Science 369, 1318\u20131330 (2020). https:\/\/doi.org\/10.1126\/science.aaz1776","DOI":"10.1126\/science.aaz1776"},{"key":"38712_CR49","doi-asserted-by":"publisher","first-page":"1258371","DOI":"10.3389\/fonc.2023.1258371","volume":"13","author":"DF Schultz","year":"2023","unstructured":"Schultz, D. F., Billadeau, D. D. & Jois, S. D. EGFR trafficking: Effect of dimerization, dynamics, and mutation. Front. Oncol. 13, 1258371. https:\/\/doi.org\/10.3389\/fonc.2023.1258371 (2023).","journal-title":"Front. Oncol."},{"key":"38712_CR50","doi-asserted-by":"publisher","first-page":"13353","DOI":"10.1074\/jbc.RA120.012852","volume":"295","author":"PO Byrne","year":"2020","unstructured":"Byrne, P. O., Hristova, K. & Leahy, D. J. EGFR forms ligand-independent oligomers that are distinct from the active state. J. Biol. Chem. 295, 13353\u201313362. https:\/\/doi.org\/10.1074\/jbc.RA120.012852 (2020).","journal-title":"J. Biol. Chem."},{"key":"38712_CR51","doi-asserted-by":"publisher","first-page":"271","DOI":"10.21873\/cgp.20501","volume":"22","author":"H Yun","year":"2025","unstructured":"Yun, H. et al. Loss of E-cadherin Activates EGFR-MEK\/ERK signaling, promoting cervical cancer progression. Cancer Genom. Proteom. 22, 271\u2013284. https:\/\/doi.org\/10.21873\/cgp.20501 (2025).","journal-title":"Cancer Genom. Proteom."},{"key":"38712_CR52","doi-asserted-by":"publisher","first-page":"1426","DOI":"10.15252\/emmm.201404976","volume":"7","author":"C He","year":"2015","unstructured":"He, C. et al. The Hippo\/YAP pathway interacts with EGFR signaling and HPV oncoproteins to regulate cervical cancer progression. EMBO Mol. Med. 7, 1426\u20131449. https:\/\/doi.org\/10.15252\/emmm.201404976 (2015).","journal-title":"EMBO Mol. Med."},{"key":"38712_CR53","doi-asserted-by":"publisher","first-page":"44","DOI":"10.1038\/s41392-024-02083-w","volume":"10","author":"Y Zhang","year":"2025","unstructured":"Zhang, Y., Qiu, K., Ren, J., Zhao, Y. & Cheng, P. Roles of human papillomavirus in cancers: Oncogenic mechanisms and clinical use. Signal Transduct. Target. Ther. 10, 44. https:\/\/doi.org\/10.1038\/s41392-024-02083-w (2025).","journal-title":"Signal Transduct. Target. Ther."},{"key":"38712_CR54","doi-asserted-by":"publisher","DOI":"10.1002\/cac2.70008","author":"X Cen","year":"2025","unstructured":"Cen, X. et al. Pan-cancer analysis shapes the understanding of cancer biology and medicine. Cancer Commun. (Lond.) https:\/\/doi.org\/10.1002\/cac2.70008 (2025).","journal-title":"Cancer Commun. (Lond.)"},{"key":"38712_CR55","doi-asserted-by":"publisher","first-page":"231","DOI":"10.1016\/j.ygeno.2012.06.011","volume":"100","author":"M-R Ho","year":"2012","unstructured":"Ho, M.-R., Tsai, K.-W. & Lin, W.-C. A unified framework of overlapping genes: Towards the origination and endogenic regulation. Genomics 100, 231\u2013239. https:\/\/doi.org\/10.1016\/j.ygeno.2012.06.011 (2012).","journal-title":"Genomics"},{"key":"38712_CR56","doi-asserted-by":"publisher","first-page":"437","DOI":"10.1186\/1471-2164-15-437","volume":"15","author":"A Choudhury","year":"2014","unstructured":"Choudhury, A. et al. Population-specific common SNPs reflect demographic histories and highlight regions of genomic plasticity with functional relevance. BMC Genom. 15, 437. https:\/\/doi.org\/10.1186\/1471-2164-15-437 (2014).","journal-title":"BMC Genom."},{"key":"38712_CR57","doi-asserted-by":"publisher","first-page":"71","DOI":"10.1001\/jama.2024.21972","volume":"333","author":"WM Association","year":"2025","unstructured":"Association, W. M. World medical association declaration of Helsinki: Ethical principles for medical research involving human participants. JAMA 333, 71\u201374. https:\/\/doi.org\/10.1001\/jama.2024.21972 (2025).","journal-title":"JAMA"},{"key":"38712_CR58","doi-asserted-by":"publisher","first-page":"W600","DOI":"10.1093\/nar\/gkp290","volume":"37","author":"Z Xu","year":"2009","unstructured":"Xu, Z. & Taylor, J. A. SNPinfo: Integrating GWAS and candidate gene information into functional SNP selection for genetic association studies. Nucleic Acids Res. 37, W600-605. https:\/\/doi.org\/10.1093\/nar\/gkp290 (2009).","journal-title":"Nucleic Acids Res."},{"key":"38712_CR59","doi-asserted-by":"publisher","first-page":"D1243","DOI":"10.1093\/nar\/gkae974","volume":"53","author":"G Perez","year":"2025","unstructured":"Perez, G. et al. The UCSC genome browser database: 2025 update. Nucleic Acids Res. 53, D1243-d1249. https:\/\/doi.org\/10.1093\/nar\/gkae974 (2025).","journal-title":"Nucleic Acids Res."},{"key":"38712_CR60","doi-asserted-by":"publisher","DOI":"10.1002\/0471142905.hg0210s56","author":"L Hui","year":"2008","unstructured":"Hui, L., DelMonte, T. & Ranade, K. Genotyping using the TaqMan assay. Curr. Protoc. Hum. Genet. https:\/\/doi.org\/10.1002\/0471142905.hg0210s56 (2008).","journal-title":"Curr. Protoc. Hum. Genet."},{"key":"38712_CR61","doi-asserted-by":"publisher","first-page":"887","DOI":"10.1086\/429864","volume":"76","author":"JE Wigginton","year":"2005","unstructured":"Wigginton, J. E., Cutler, D. J. & Abecasis, G. R. A note on exact tests of Hardy-Weinberg equilibrium. Am. Human Genet. 76, 887\u2013893. https:\/\/doi.org\/10.1086\/429864 (2005).","journal-title":"Am. Human Genet."},{"key":"38712_CR62","unstructured":"Wells, G., Shea, B. & O\u2019Connell, J. The Newcastle-Ottawa Scale (NOS) for assessing the quality of nonrandomised studies in Meta-analyses. Ottawa Health Res. Inst. Web site 7 (2014)."},{"key":"38712_CR63","unstructured":"IBM Corp. Released 2019. IB SPSS Statistics forWindows, Version 26.0. (IBM Corp., Armonk)."},{"key":"38712_CR64","doi-asserted-by":"publisher","first-page":"256","DOI":"10.12691\/ajme-1-7-21","volume":"1","author":"E Ostertagovc","year":"2013","unstructured":"Ostertagovc, E. & Ostertag, O. Methodology and application of oneway ANOVA. Am. J. Mech. Eng. 1, 256\u2013261. https:\/\/doi.org\/10.12691\/ajme-1-7-21 (2013).","journal-title":"Am. J. Mech. Eng."},{"key":"38712_CR65","doi-asserted-by":"publisher","first-page":"97","DOI":"10.1038\/sj.cr.7290272","volume":"15","author":"YY Shi","year":"2005","unstructured":"Shi, Y. Y. & He, L. SHEsis, a powerful software platform for analyses of linkage disequilibrium, haplotype construction, and genetic association at polymorphism loci. Cell Res. 15, 97\u201398. https:\/\/doi.org\/10.1038\/sj.cr.7290272 (2005).","journal-title":"Cell Res."},{"key":"38712_CR66","doi-asserted-by":"publisher","first-page":"170","DOI":"10.1136\/bmj.310.6973.170","volume":"310","author":"JM Bland","year":"1995","unstructured":"Bland, J. M. & Altman, D. G. Multiple significance tests: the Bonferroni method. BMJ 310, 170. https:\/\/doi.org\/10.1136\/bmj.310.6973.170 (1995).","journal-title":"BMJ"},{"key":"38712_CR67","doi-asserted-by":"publisher","first-page":"589","DOI":"10.1016\/s0197-2456(98)00037-3","volume":"19","author":"WD Dupont","year":"1998","unstructured":"Dupont, W. D. & Plummer, W. D. Jr. Power and sample size calculations for studies involving linear regression. Control Clin. Trials 19, 589\u2013601. https:\/\/doi.org\/10.1016\/s0197-2456(98)00037-3 (1998).","journal-title":"Control Clin. Trials"},{"key":"38712_CR68","doi-asserted-by":"publisher","first-page":"1928","DOI":"10.1093\/bioinformatics\/btl268","volume":"22","author":"X Sol\u00e9","year":"2006","unstructured":"Sol\u00e9, X., Guin\u00f3, E., Valls, J., Iniesta, R. & Moreno, V. SNPStats: A web tool for the analysis of association studies. Bioinformatics 22, 1928\u20131929. https:\/\/doi.org\/10.1093\/bioinformatics\/btl268 (2006).","journal-title":"Bioinformatics"},{"key":"38712_CR69","doi-asserted-by":"publisher","first-page":"396","DOI":"10.2174\/1389202917666160513102612","volume":"17","author":"HM Xu","year":"2016","unstructured":"Xu, H. M. et al. GMDR: Versatile software for detecting gene-gene and gene-environ- ment interactions underlying complex traits. Curr Genom. 17, 396\u2013402. https:\/\/doi.org\/10.2174\/1389202917666160513102612 (2016).","journal-title":"Curr Genom."},{"key":"38712_CR70","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0016981","volume":"6","author":"GB Chen","year":"2011","unstructured":"Chen, G. B. et al. Practical and theoretical considerations in study design for detecting gene-gene interactions using MDR and GMDR approaches. PLoS ONE 6, e16981. https:\/\/doi.org\/10.1371\/journal.pone.0016981 (2011).","journal-title":"PLoS ONE"},{"key":"38712_CR71","volume-title":"Stata Statistical Software: Release 17","author":"StataCorp","year":"2021","unstructured":"StataCorp. Stata Statistical Software: Release 17 (StataCorp LLC, College Station, 2021)."},{"key":"38712_CR72","doi-asserted-by":"publisher","first-page":"1088","DOI":"10.2307\/2533446","volume":"50","author":"CB Begg","year":"1994","unstructured":"Begg, C. B. & Mazumdar, M. Operating characteristics of a rank correlation test for publication bias. Biometrics 50, 1088\u20131101 (1994).","journal-title":"Biometrics"}],"container-title":["Scientific Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41598-026-38712-3","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-026-38712-3.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-026-38712-3.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,3,17]],"date-time":"2026-03-17T01:02:25Z","timestamp":1773709345000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41598-026-38712-3"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,2,14]]},"references-count":72,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2026,12]]}},"alternative-id":["38712"],"URL":"https:\/\/doi.org\/10.1038\/s41598-026-38712-3","relation":{},"ISSN":["2045-2322"],"issn-type":[{"value":"2045-2322","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,2,14]]},"assertion":[{"value":"22 August 2025","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"30 January 2026","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"14 February 2026","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"The authors declare no competing interests.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}},{"value":"The study has been approved by the Ethics Committee of the Third Affiliated Hospital of Kunming Medical University (No. KYCS2021193). All patients signed an informed consent form allowing the conservation and study of their biological samples.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"Not applicable.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}}],"article-number":"9051"}}