{"doi":"10.1002/mc.22955","title":"SNP‐SNP and SNP‐environment interactions of potentially functional <i>HOTAIR</i> SNPs modify the risk of hepatocellular carcinoma","abstract":"<jats:sec><jats:label/><jats:p>HOX transcript antisense intergenic RNA (<jats:italic>HOTAIR</jats:italic>) has been widely regarded as a functional lncRNA contributing to multiple cancers. However, few studies have examined the effect of single nucleotide polymorphisms (SNPs) in <jats:italic>HOTAIR</jats:italic> on the occurrence and development of hepatocellular carcinoma (HCC). In this study, three potentially functional <jats:italic>HOTAIR</jats:italic> SNPs (rs17105613, rs12427129, and rs3816153) were selected using bioinformatic tools. A case‐control study including 1262 cases and 1559 controls was conducted to explore the association of <jats:italic>HOTAIR</jats:italic> SNPs with the risk of HCC in a Southern Chinese population. We found that SNPs rs12427129 and rs3816153 were associated with the risk of HCC in dominant genetic models (CC: CT + TT, adjusted odds ratio (OR) = 0.72, 95% confidence interval (CI) = 0.57–0.90 and GG: GT + TT, adjusted OR = 1.30, 95%CI = 1.08–1.57). Additionally, SNP–environment interactions for rs12427129, rs3816153, and HBsAg status were found to enhance the risk of HCC, with FDR‐<jats:italic>P</jats:italic> as an additive interaction equal to 0.0006 and 0.0144, respectively. In multifactor dimensionality reduction (MDR) analysis, the three‐factor model (HBsAg status, rs12427129 and rs3816153) yielded the highest test accuracy of 77.74% (permutation <jats:italic>P </jats:italic>&lt; 0.001). Interestingly, the effect of rs12427129 and rs3816153 on the risk of HCC could be modified by HBsAg status, while the rs12427129 CT/TT genotype could antagonize the detrimental effect of rs3816153 GT/TT genotype on HCC. Our findings suggest that rs12427129 and rs3816153, including their SNP‐SNP and SNP‐environment interaction with HBsAg status, potentially play important roles on the susceptibility to HCC.</jats:p></jats:sec>","journal":"Molecular Carcinogenesis","year":2019,"id":634598,"datarank":0.6064576901751826,"base_score":4.04305126783455,"endowment":4.04305126783455,"self_citation_contribution":0.6064576901751826,"citation_network_contribution":0.0,"self_endowment_contribution":0.6064576901751826,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":56,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":25,"is_dataset":false,"is_dataset_confidence":null,"is_data_producer":false,"deposit_databanks":null,"is_oa":false,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":null,"fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1064426,"name":"Li Liu","orcid":"0000-0001-6126-2635","position":1,"is_corresponding":false},{"id":1645943,"name":"Zhifeng Lin","orcid":null,"position":2,"is_corresponding":false},{"id":487695,"name":"Xiaohui Ji","orcid":null,"position":3,"is_corresponding":false},{"id":1645949,"name":"Lucheng Pi","orcid":null,"position":4,"is_corresponding":false},{"id":1645952,"name":"Xinqi Lin","orcid":null,"position":5,"is_corresponding":false},{"id":1645954,"name":"Nana Tian","orcid":null,"position":6,"is_corresponding":false},{"id":1645956,"name":"Guiyan Liu","orcid":null,"position":7,"is_corresponding":false},{"id":1267789,"name":"Qing Liu","orcid":"0000-0002-7046-0307","position":8,"is_corresponding":false},{"id":706400,"name":"Ziqiang Lin","orcid":"0000-0003-1990-6788","position":9,"is_corresponding":false},{"id":1645957,"name":"Sidong Chen","orcid":null,"position":10,"is_corresponding":false},{"id":1645958,"name":"Xinfa Yu","orcid":null,"position":11,"is_corresponding":false},{"id":1645959,"name":"Yanhui Gao","orcid":null,"position":12,"is_corresponding":false},{"id":1645940,"name":"Junguo Zhang","orcid":"0000-0001-9421-2423","position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"resolved":true,"title":"SNP‐SNP and SNP‐environment interactions of potentially functional <i>HOTAIR</i> SNPs modify the risk of hepatocellular carcinoma","abstract":"<jats:sec><jats:label/><jats:p>HOX transcript antisense intergenic RNA (<jats:italic>HOTAIR</jats:italic>) has been widely regarded as a functional lncRNA contributing to multiple cancers. However, few studies have examined the effect of single nucleotide polymorphisms (SNPs) in <jats:italic>HOTAIR</jats:italic> on the occurrence and development of hepatocellular carcinoma (HCC). In this study, three potentially functional <jats:italic>HOTAIR</jats:italic> SNPs (rs17105613, rs12427129, and rs3816153) were selected using bioinformatic tools. A case‐control study including 1262 cases and 1559 controls was conducted to explore the association of <jats:italic>HOTAIR</jats:italic> SNPs with the risk of HCC in a Southern Chinese population. We found that SNPs rs12427129 and rs3816153 were associated with the risk of HCC in dominant genetic models (CC: CT + TT, adjusted odds ratio (OR) = 0.72, 95% confidence interval (CI) = 0.57–0.90 and GG: GT + TT, adjusted OR = 1.30, 95%CI = 1.08–1.57). Additionally, SNP–environment interactions for rs12427129, rs3816153, and HBsAg status were found to enhance the risk of HCC, with FDR‐<jats:italic>P</jats:italic> as an additive interaction equal to 0.0006 and 0.0144, respectively. In multifactor dimensionality reduction (MDR) analysis, the three‐factor model (HBsAg status, rs12427129 and rs3816153) yielded the highest test accuracy of 77.74% (permutation <jats:italic>P </jats:italic>&lt; 0.001). Interestingly, the effect of rs12427129 and rs3816153 on the risk of HCC could be modified by HBsAg status, while the rs12427129 CT/TT genotype could antagonize the detrimental effect of rs3816153 GT/TT genotype on HCC. Our findings suggest that rs12427129 and rs3816153, including their SNP‐SNP and SNP‐environment interaction with HBsAg status, potentially play important roles on the susceptibility to HCC.</jats:p></jats:sec>","is_dataset_classified":null,"base_score":4.04305126783455,"endowment":4.04305126783455,"datacite_reuse_total":25,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"30556621","pmcid":null,"openalex_id":"https://openalex.org/W2904996491","authors":[],"funders":[{"funder_name":"Natural Science Foundation of Guangdong Province","grant_id":"Grant No. 2016A030313809","title":null},{"funder_name":"National Natural Science Foundation of China","grant_id":"Grant No. 71573059","title":null},{"funder_name":"The Science and Technology Plan Project of Guangdong Province","grant_id":"Grant No. 2014A020212307","title":null},{"funder_name":"The Training Programme for Outstanding Young Teachers in Higher Education Institutions of Guangdong Province","grant_id":"Grant No. YQ2015098","title":null}],"total_grants":4,"fwci":3.5538,"citation_percentile":0.94206339,"influential_citations":1,"citation_trend":[{"year":2019,"count":3},{"year":2020,"count":4},{"year":2021,"count":38},{"year":2022,"count":1},{"year":2023,"count":3},{"year":2024,"count":2},{"year":2025,"count":5}],"oa_status":"closed","license":"http://onlinelibrary.wiley.com/termsAndConditions#vor","oa_locations":[{"url":"https://api.wiley.com/onlinelibrary/tdm/v1/articles/10.1002%2Fmc.22955","host_type":"publisher"},{"url":"https://onlinelibrary.wiley.com/doi/pdf/10.1002/mc.22955","host_type":"publisher"},{"url":"https://onlinelibrary.wiley.com/doi/full-xml/10.1002/mc.22955","host_type":"publisher"},{"url":"https://doi.org/10.1002/mc.22955","host_type":"journal"},{"url":"https://pubmed.ncbi.nlm.nih.gov/30556621","host_type":"repository"}],"fields_of_study":["Cancer-related molecular mechanisms research","RNA Research and Splicing","Circular RNAs in diseases","Biology","Medicine","Asian People","Biomarkers, Tumor","Carcinoma, Hepatocellular","Case-Control Studies","Female","Follow-Up Studies","Gene-Environment Interaction","Genetic Predisposition to Disease","Genotype","Hepatitis B Surface Antigens","Humans","Liver Neoplasms","Male","Middle Aged","Polymorphism, Single Nucleotide","Prognosis","RNA, Long Noncoding","Risk Factors"],"mesh_terms":["Female","Follow-Up Studies","Genotype","Hepatitis B Surface Antigens","Carcinoma, Hepatocellular","Humans","Liver Neoplasms","Male","Middle Aged","Prognosis","Risk Factors","Biomarkers, Tumor","Case-Control Studies","Genetic Predisposition to Disease","Polymorphism, Single Nucleotide","Asian People","Gene-Environment Interaction","RNA, Long Noncoding"],"keywords":["HOTAIR","Single-nucleotide polymorphism","SNP","Biology","Hepatocellular carcinoma","Odds ratio","Genotype","Multifactor dimensionality reduction","Long non-coding RNA","Oncology","Case-control study","Internal medicine","Genetics","Medicine","Gene","RNA","Gene-environment Interaction","Functional Annotation","Genetic Variant"],"sdg_mappings":[],"linked_datasets":[{"doi":"10.6084/m9.figshare.14936580.v1","title":"Additional file 10 of Genetic expression and mutational profile analysis in different pathologic stages of hepatocellular carcinoma patients","publisher":"figshare","resource_type":"JournalArticle"},{"doi":"10.6084/m9.figshare.14936580","title":"Additional file 10 of Genetic expression and mutational profile analysis in different pathologic stages of hepatocellular carcinoma patients","publisher":"figshare","resource_type":"JournalArticle"},{"doi":"10.6084/m9.figshare.14936583.v1","title":"Additional file 11 of Genetic expression and mutational profile analysis in different pathologic stages of hepatocellular carcinoma patients","publisher":"figshare","resource_type":"JournalArticle"},{"doi":"10.6084/m9.figshare.14936583","title":"Additional file 11 of Genetic expression and mutational profile analysis in different pathologic stages of hepatocellular carcinoma patients","publisher":"figshare","resource_type":"JournalArticle"},{"doi":"10.6084/m9.figshare.14936586.v1","title":"Additional file 12 of Genetic expression and mutational profile analysis in different pathologic stages of hepatocellular carcinoma patients","publisher":"figshare","resource_type":"JournalArticle"},{"doi":"10.6084/m9.figshare.14936586","title":"Additional file 12 of Genetic expression and mutational profile analysis in different pathologic stages of hepatocellular carcinoma patients","publisher":"figshare","resource_type":"JournalArticle"},{"doi":"10.6084/m9.figshare.14936589.v1","title":"Additional file 13 of Genetic expression and mutational profile analysis in different pathologic stages of hepatocellular carcinoma patients","publisher":"figshare","resource_type":"JournalArticle"},{"doi":"10.6084/m9.figshare.14936589","title":"Additional file 13 of Genetic expression and mutational profile analysis in different pathologic stages of hepatocellular carcinoma patients","publisher":"figshare","resource_type":"JournalArticle"},{"doi":"10.6084/m9.figshare.14936592.v1","title":"Additional file 14 of Genetic expression and mutational profile analysis in different pathologic stages of hepatocellular carcinoma patients","publisher":"figshare","resource_type":"JournalArticle"},{"doi":"10.6084/m9.figshare.14936592","title":"Additional file 14 of Genetic expression and mutational profile analysis in different pathologic stages of hepatocellular carcinoma patients","publisher":"figshare","resource_type":"JournalArticle"},{"doi":"10.6084/m9.figshare.14936595.v1","title":"Additional file 15 of Genetic expression and mutational profile analysis in different pathologic stages of hepatocellular carcinoma patients","publisher":"figshare","resource_type":"JournalArticle"},{"doi":"10.6084/m9.figshare.14936595","title":"Additional file 15 of Genetic expression and mutational profile analysis in different pathologic stages of hepatocellular carcinoma patients","publisher":"figshare","resource_type":"JournalArticle"},{"doi":"10.6084/m9.figshare.14936598.v1","title":"Additional file 16 of Genetic expression and mutational profile analysis in different pathologic stages of hepatocellular carcinoma patients","publisher":"figshare","resource_type":"JournalArticle"},{"doi":"10.6084/m9.figshare.14936598","title":"Additional file 16 of Genetic expression and mutational profile analysis in different pathologic stages of hepatocellular carcinoma patients","publisher":"figshare","resource_type":"JournalArticle"},{"doi":"10.6084/m9.figshare.14936601.v1","title":"Additional file 1 of Genetic expression and mutational profile analysis in different pathologic stages of hepatocellular carcinoma patients","publisher":"figshare","resource_type":"JournalArticle"},{"doi":"10.6084/m9.figshare.14936601","title":"Additional file 1 of Genetic expression and mutational profile analysis in different pathologic stages of hepatocellular carcinoma patients","publisher":"figshare","resource_type":"JournalArticle"},{"doi":"10.6084/m9.figshare.14936604.v1","title":"Additional file 2 of Genetic expression and mutational profile analysis in different pathologic stages of hepatocellular carcinoma patients","publisher":"figshare","resource_type":"JournalArticle"},{"doi":"10.6084/m9.figshare.14936604","title":"Additional file 2 of Genetic expression and mutational profile analysis in different pathologic stages of hepatocellular carcinoma patients","publisher":"figshare","resource_type":"JournalArticle"},{"doi":"10.6084/m9.figshare.14936607.v1","title":"Additional file 3 of Genetic expression and mutational profile analysis in different pathologic stages of hepatocellular carcinoma patients","publisher":"figshare","resource_type":"JournalArticle"},{"doi":"10.6084/m9.figshare.14936607","title":"Additional file 3 of Genetic expression and mutational profile analysis in different pathologic stages of hepatocellular carcinoma patients","publisher":"figshare","resource_type":"JournalArticle"},{"doi":"10.6084/m9.figshare.14936610.v1","title":"Additional file 4 of Genetic expression and mutational profile analysis in different pathologic stages of hepatocellular carcinoma patients","publisher":"figshare","resource_type":"JournalArticle"},{"doi":"10.6084/m9.figshare.14936610","title":"Additional file 4 of Genetic expression and mutational profile analysis in different pathologic stages of hepatocellular carcinoma patients","publisher":"figshare","resource_type":"JournalArticle"},{"doi":"10.6084/m9.figshare.14936613.v1","title":"Additional file 5 of Genetic expression and mutational profile analysis in different pathologic stages of hepatocellular carcinoma patients","publisher":"figshare","resource_type":"JournalArticle"},{"doi":"10.6084/m9.figshare.14936613","title":"Additional file 5 of Genetic expression and mutational profile analysis in different pathologic stages of hepatocellular carcinoma patients","publisher":"figshare","resource_type":"JournalArticle"},{"doi":"10.6084/m9.figshare.14936616.v1","title":"Additional file 6 of Genetic expression and mutational profile analysis in different pathologic stages of hepatocellular carcinoma patients","publisher":"figshare","resource_type":"JournalArticle"}],"clinical_trials":[],"software_tools":[],"database_accessions":[{"name":"refsnp"}],"source":"live","citation_network_status":"fetched"},"created_at":"2026-08-06T13:53:21.950659Z","pmid":null,"pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}