Carcinogenesis最新文献

The Oncogenic Role of AURKA in Gastric Cancer: Mechanisms, Pathways, and Clinical Relevance. AURKA在胃癌中的致癌作用：机制、途径和临床相关性。

IF 2.9 3区医学

Carcinogenesis Pub Date : 2025-09-09 DOI: 10.1093/carcin/bgaf054

Caixia Lv, Yan Liu, Huanhu Zhang

{"title":"The Oncogenic Role of AURKA in Gastric Cancer: Mechanisms, Pathways, and Clinical Relevance.","authors":"Caixia Lv, Yan Liu, Huanhu Zhang","doi":"10.1093/carcin/bgaf054","DOIUrl":"https://doi.org/10.1093/carcin/bgaf054","url":null,"abstract":"Aurora kinase A (AURKA) is a serine/threonine kinase that plays a critical role in cell cycle regulation, particularly during mitosis. Recent studies have identified AURKA as an oncogene overexpressed in various cancers, including gastric cancer (GC). This review summarizes the molecular mechanisms by which AURKA contributes to GC pathogenesis, including its roles in cell proliferation, apoptosis inhibition, epithelial-mesenchymal transition (EMT), and cancer stemness. AURKA regulates key signaling pathways such as PI3K/Akt, Wnt/β-catenin, NF-κB, and JAK2/STAT3, promoting tumor growth, metastasis, and therapy resistance. Additionally, AURKA interacts with critical tumor suppressors like p53 and PTEN, further enhancing its oncogenic potential. Clinical studies have demonstrated that AURKA overexpression correlates with poor prognosis in GC patients, highlighting its potential as a diagnostic and therapeutic target. This review also discusses the efficacy of AURKA inhibitors in preclinical settings, offering insights into their therapeutic potential. By elucidating the multifaceted roles of AURKA in GC, this review aims to provide a comprehensive understanding of its mechanisms and implications for future research and treatment strategies.","PeriodicalId":9446,"journal":{"name":"Carcinogenesis","volume":" ","pages":""},"PeriodicalIF":2.9,"publicationDate":"2025-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145022907","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Epithelial Ikkβ deletion modulates immune responses and the IFNγ/CXCL9 axis during early esophageal carcinogenesis. 在早期食管癌发生过程中，上皮Ikkβ缺失调节免疫反应和IFNγ/CXCL9轴。

IF 2.9 3区医学

Carcinogenesis Pub Date : 2025-09-08 DOI: 10.1093/carcin/bgaf055

Nathan Hodge, Marie-Pier Tétreault

{"title":"Epithelial Ikkβ deletion modulates immune responses and the IFNγ/CXCL9 axis during early esophageal carcinogenesis.","authors":"Nathan Hodge, Marie-Pier Tétreault","doi":"10.1093/carcin/bgaf055","DOIUrl":"10.1093/carcin/bgaf055","url":null,"abstract":"Esophageal cancer is a major cause of cancer-related death, often preceded with chronic inflammation and injuries. The NFκB/IKKβ pathway plays a central role in inflammation, yet its role in early esophageal carcinogenesis remains unclear. This study investigated the role of epithelial IKKβ in early esophageal carcinogenesis. Mice were treated with the carcinogen 4-nitroquinoline-1-oxide (4-NQO) or a vehicle for one month to induce precancerous lesions. Esophagi were harvested and examined through histological, protein, flow cytometry, and RNA analyses. Histological analysis revealed that 4-NQO treatment led to increased inflammation, intraepithelial CD45+ immune cells, and elevated IKKβ phosphorylation levels. Mice with esophageal epithelial-specific Ikkβ deletion (4-NQO/IkkβEEC-KO) showed delayed progression to a precancerous state, with reduced immune cell recruitment compared to 4-NQO/controls. Immunophenotyping showed decreased recruitment of T cells, including CD4+, CD8+ and regulatory (Tregs) T cells, and increased recruitment of macrophages in 4-NQO/IkkβEEC-KO mice compared to 4-NQO/controls. RNA sequencing data identified 262 differentially expressed genes in 4-NQO/IkkβEEC-KO mice, implicating pathways related to inflammation and wound healing. Notably, the chemokine CXCL9, a T cell chemoattractant, was significantly upregulated in 4-NQO control mice, but not in 4-NQO/IkkβEEC-KO mice. Further analysis identified IFNγ as an upstream regulator of Cxcl9 expression, and neutralization of IFNγ reduced Cxcl9 expression levels in 4-NQO treated mice. Additionally, in vitro studies demonstrated that IFNγ upregulates Cxcl9 in an NF-ĸB dependent manner in esophageal keratinocytes. These findings suggest that epithelial IKKβ regulates the immune microenvironment in early esophageal carcinogenesis through the IFNγ/CXCL9 axis and influencing T cell recruitment and inflammatory responses.","PeriodicalId":9446,"journal":{"name":"Carcinogenesis","volume":" ","pages":""},"PeriodicalIF":2.9,"publicationDate":"2025-09-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145013749","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

FZD6 promotes 5-fluorouracil resistance through inhibiting pyroptosis in colorectal cancer. FZD6通过抑制结直肠癌焦亡促进5-氟尿嘧啶耐药。

IF 2.9 3区医学

Carcinogenesis Pub Date : 2025-09-04 DOI: 10.1093/carcin/bgaf041

Zilong He, Jing Yang, Yu Zhang, TongXin Zhang, Tao Guo, Linfang Jin, Yong Mao, Teng Wang

{"title":"FZD6 promotes 5-fluorouracil resistance through inhibiting pyroptosis in colorectal cancer.","authors":"Zilong He, Jing Yang, Yu Zhang, TongXin Zhang, Tao Guo, Linfang Jin, Yong Mao, Teng Wang","doi":"10.1093/carcin/bgaf041","DOIUrl":"10.1093/carcin/bgaf041","url":null,"abstract":"Resistance to 5-fluorouracil (5-FU) causes treatment failure in most colorectal cancer (CRC) cases. Pyroptosis is associated with chemotherapy resistance, although its role in 5-FU resistance in CRC is not well understood. To investigate this, we performed proteomic sequencing and bioinformatics analysis on wild-type and 5-FU-resistant CRC cell lines. Subsequently, Frizzled receptor 6 (FZD6) knockdown and overexpression cell lines were established using a lentiviral system. CCK-8, colony formation, and EdU assays were performed to assess the viability and proliferative potential of 5-FU-treated cells. The morphological changes associated with pyroptosis were examined by microscopic imaging and electron microscopy. The nuclear expression of β-catenin was examined by immunofluorescence and western blotting. These findings indicated that FZD6 protein was upregulated in the 5-FU-resistant CRC cells compared with the corresponding wild-type cell lines, an observation further validated through immunohistochemical analysis of clinical samples. Additionally, 5-FU treatment induced NLRP3/caspase-1/GSDMD-mediated classical pyroptosis in the wild-type CRC cells and decreased their viability, while the pyroptosis inhibitor Ac-FITD-CMK enhanced drug resistance. Furthermore, overexpression of FZD6 promoted nuclear translocation of β-catenin, reduced pyroptosis, and increased 5-FU resistance. In contrast, 5-FU treatment did not induce significant pyroptosis in drug-resistant cells, while pyroptosis inducers (nigericin or LPS + ATP) significantly reduced cell viability regardless of 5-FU. Moreover, knockdown of FZD6 decreased nuclear translocation of β-catenin, enhanced pyroptosis, and reduced 5-FU resistance. Finally, β-catenin knockdown enhanced pyroptosis and decreased 5-FU resistance. Thus, FZD6 promotes 5-FU resistance in CRC cells by inhibiting pyroptosis through increased nuclear translocation of β-catenin.","PeriodicalId":9446,"journal":{"name":"Carcinogenesis","volume":" ","pages":""},"PeriodicalIF":2.9,"publicationDate":"2025-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144854613","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Longitudinal single-cell RNA model aids prediction of EGFR-TKI resistance. 纵向单细胞RNA模型有助于预测EGFR-TKI耐药性。

IF 2.9 3区医学

Carcinogenesis Pub Date : 2025-09-04 DOI: 10.1093/carcin/bgaf038

Guoxin Hou, Zhimin Lu, Dongqiang Zeng, Qican Chen, Subing Cheng, Binbin Song

{"title":"Longitudinal single-cell RNA model aids prediction of EGFR-TKI resistance.","authors":"Guoxin Hou, Zhimin Lu, Dongqiang Zeng, Qican Chen, Subing Cheng, Binbin Song","doi":"10.1093/carcin/bgaf038","DOIUrl":"10.1093/carcin/bgaf038","url":null,"abstract":"Resistance is inevitable and a major challenge in treating lung adenocarcinoma (LUAD) patients with EGFR mutations. This study aimed to investigate the mechanism of EGFR-TKI resistance in LUAD using longitudinal single-cell RNA sequencing (scRNA-seq) data. We collected tumour samples of LUAD patients before and after EGFR inhibitor treatment and performed single-cell RNA sequencing. We used machine learning models for cell annotation and classified cells into subgroups. The inferCNV algorithm was used for CNV score calculation and tumour cell identification, and metabolic analysis was done using a gene-scoring approach. EGFR resistance score (ERscore), a gene signature derived from resistant tumour cells, was established to evaluate the predictiveness to EGFR-TKI inhibitors. The investigation classified subgroups of cells and identified three tumour cell types as critical cells mediating EGFR-TKI resistance. Our data also analysed the metabolic aspects of EGFR-TKI resistance using a single-cell approach. It showed that some tumour cell subtypes had a consistent metabolic profile, significantly up-regulating purine metabolism, oxidative phosphorylation, glycogen, and lipid metabolism. An assessment system called ERscore was established to evaluate the association between EGFR-TKI resistance and tumour ecosystem. The analysis showed a significant correlation between the ERscore and EGFR-TKI resistance, lung cancer phenotype, and prognosis. The findings suggest that the molecular mechanisms driving EGFR-TKI resistance in lung cancer may also contribute to poorer prognosis, particularly in lung adenocarcinomas with high EGFR mutation rates. Overall, the study provides important insights into the mechanisms of EGFR-TKI resistance in lung cancer at the single-cell level.","PeriodicalId":9446,"journal":{"name":"Carcinogenesis","volume":" ","pages":""},"PeriodicalIF":2.9,"publicationDate":"2025-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144752498","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Targeted sequencing and functional interrogation identified novel variant at 12q14.2 associated with risk of ovarian cancer in Han Chinese women. 靶向测序和功能询问鉴定了中国汉族女性卵巢癌风险相关的12q14.2新变异。

IF 2.9 3区医学

Carcinogenesis Pub Date : 2025-09-04 DOI: 10.1093/carcin/bgaf037

Yanrui Zhao, Wei Geng, Wei Liu, Lei Liu, Changcai Teng, Yuxin Chen, Dong Yang, Linqing Chai, Wei Wang, Xinlei Chu, Caiyun Huang, Ben Liu, Kexin Chen, Hong Zheng, Lian Li

{"title":"Targeted sequencing and functional interrogation identified novel variant at 12q14.2 associated with risk of ovarian cancer in Han Chinese women.","authors":"Yanrui Zhao, Wei Geng, Wei Liu, Lei Liu, Changcai Teng, Yuxin Chen, Dong Yang, Linqing Chai, Wei Wang, Xinlei Chu, Caiyun Huang, Ben Liu, Kexin Chen, Hong Zheng, Lian Li","doi":"10.1093/carcin/bgaf037","DOIUrl":"10.1093/carcin/bgaf037","url":null,"abstract":"Chromosome 12q14.2 has been reported as a potential risk locus for epithelial ovarian cancer (EOC) in genome-wide association study (GWAS). We performed targeted sequencing around the rs11175194 at chromosome 12q14.2 and identified five potential risk variants. The association between these five variants and EOC risk was evaluated in 893 EOC cases and 1292 controls. We identified that rs11175195 (P = 1.94 × 10-6, OR = 1.36, 95% CI = 1.20-1.54) was significantly associated with EOC risk in validation study and after meta-analysis with previous GWAS data, rs11175195 reached genome-wide significant level (P < 5 × 10-8). Functional annotation and expression quantitative trait loci analysis prioritized rs11175194 as a causal variant at this locus. The presence of G-rs11175194 risk allele increased binding affinity of the transcription factor NR1H4 and upregulate SRGAP1 gene expression. Overexpression of SRGAP1 promotes the proliferation and invasion in ovarian cancer cell lines. In conclusion, we identified a novel susceptibility locus of ovarian cancer and revealed a potential molecular mechanism for ovarian cancer carcinogenesis. These results may provide a potential biomarker and therapeutic target for ovarian cancer.","PeriodicalId":9446,"journal":{"name":"Carcinogenesis","volume":" ","pages":""},"PeriodicalIF":2.9,"publicationDate":"2025-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144728110","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Core transcriptional regulatory circuit-regulated IGF2BP3 stabilizes E2F2 mRNA via m6A modification in neuroblastoma. 核心转录调控回路调控的IGF2BP3通过m6A修饰稳定神经母细胞瘤中的E2F2 mRNA。

IF 2.9 3区医学

Carcinogenesis Pub Date : 2025-09-04 DOI: 10.1093/carcin/bgaf040

Pengcheng Yang, Jianwei Wang, Ziheng Wu, Ran Zhuo, Yanling Chen, Gen Li, Yanfang Tao, Xiaolu Li, Fang Fang, Di Wu, Yang Yang, Hongli Yin, Guanghui Qian, Hairong Wang, Xin Li, Juanjuan Yu, Randong Yang, Yunyun Xu, Zhiheng Li, Lei Shi, Zimu Zhang, Jian Pan, Jian Wang

{"title":"Core transcriptional regulatory circuit-regulated IGF2BP3 stabilizes E2F2 mRNA via m6A modification in neuroblastoma.","authors":"Pengcheng Yang, Jianwei Wang, Ziheng Wu, Ran Zhuo, Yanling Chen, Gen Li, Yanfang Tao, Xiaolu Li, Fang Fang, Di Wu, Yang Yang, Hongli Yin, Guanghui Qian, Hairong Wang, Xin Li, Juanjuan Yu, Randong Yang, Yunyun Xu, Zhiheng Li, Lei Shi, Zimu Zhang, Jian Pan, Jian Wang","doi":"10.1093/carcin/bgaf040","DOIUrl":"10.1093/carcin/bgaf040","url":null,"abstract":"Neuroblastoma (NB) is a pediatric tumor with diverse outcomes and unknown underlying mechanisms. The core transcriptional regulatory circuit (CRC) and N6-methyladenosine (m6A) are key factors that control cell identity and fate. IGF2BP3 is an m6A reader protein that is transcriptionally regulated by CRC transcription factors (TFs). In NB, this molecule is abundantly expressed, and there is a clear correlation between its expression and a bad prognosis. We mechanistically demonstrated that IGF2BP3 promotes E2F2 mRNA expression through m6A, which is correlated with high risk and poor prognosis in NB patients. We showed that the CRC TF-IGF2BP3-E2F2 regulatory axis forms an oncogenic network that drives NB development and progression. Overall, we investigated the molecular mechanism by which IGF2BP3, a m6A-reading protein that is regulated by CRC TFs, regulates E2F2 mRNA expression in an m6A-dependent manner. This study highlights the therapeutic potential of disrupting this axis with m6A-targeted interventions.","PeriodicalId":9446,"journal":{"name":"Carcinogenesis","volume":" ","pages":""},"PeriodicalIF":2.9,"publicationDate":"2025-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12477426/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144871621","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Correction to: p62/SQSTM1 interacts with vimentin to enhance breast cancer metastasis. 修正：p62/SQSTM1与vimentin相互作用促进乳腺癌转移

IF 2.9 3区医学

Carcinogenesis Pub Date : 2025-09-04 DOI: 10.1093/carcin/bgaf042

引用次数: 0

Mammary Adipose Dysfunction in the Dual Epidemic of Obesity and Breast Cancer. 肥胖和乳腺癌双重流行中的乳腺脂肪功能障碍。

IF 2.9 3区医学

Carcinogenesis Pub Date : 2025-09-03 DOI: 10.1093/carcin/bgaf053

Elvina Jeyakumar, Sathyavathi Sundararaju, Stephanie Annett, Mohamed A Elrayess

{"title":"Mammary Adipose Dysfunction in the Dual Epidemic of Obesity and Breast Cancer.","authors":"Elvina Jeyakumar, Sathyavathi Sundararaju, Stephanie Annett, Mohamed A Elrayess","doi":"10.1093/carcin/bgaf053","DOIUrl":"https://doi.org/10.1093/carcin/bgaf053","url":null,"abstract":"Breast cancer is one of the leading causes of death among women, with obesity being a significant factor. Mammary adipose tissue (MAT) dysfunction in obesity creates a tumor-supportive environment, leading to increased risk. In obesity, MAT undergoes significant changes, including increased adiposity, chronic inflammation, aromatase overexpression, insulin resistance, and altered adipokine signaling, collectively fostering a pro-tumorigenic microenvironment. The interaction between adipocytes and cancer cells further exacerbates breast cancer progression through metabolic crosstalk and immune evasion. This review examines the role of MAT dysfunction in breast cancer incidence and progression, in obesity. Interestingly, obesity appears have a paradoxical effect on breast cancer risk, offering a potentially protective role in premenopausal women, but increased risk in post-menopausal women, primarily due to differences in estrogen levels. Addressing the metabolic, inflammatory, and hormonal abnormalities in obese MAT can aid in enabling the development of precision therapies that reduce breast cancer risk and improve treatment outcomes in obese patients.","PeriodicalId":9446,"journal":{"name":"Carcinogenesis","volume":" ","pages":""},"PeriodicalIF":2.9,"publicationDate":"2025-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144943888","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Δ133p53 isoform enhances TLR4 function to promote tumour growth. Δ133p53亚型增强TLR4功能，促进肿瘤生长。

IF 2.9 3区医学

Carcinogenesis Pub Date : 2025-08-29 DOI: 10.1093/carcin/bgaf051

Sasini Polwatta Lekamlage, Alexandra N Boix De Jesus, Adriana Machado Saraiva, Catherine Drummond, Harrison Dolan, Francesc March de Ribot, Janice A Royds, Sunali Mehta, Antony W Braithwaite, Noelyn A Hung, Tania L Slatter

{"title":"Δ133p53 isoform enhances TLR4 function to promote tumour growth.","authors":"Sasini Polwatta Lekamlage, Alexandra N Boix De Jesus, Adriana Machado Saraiva, Catherine Drummond, Harrison Dolan, Francesc March de Ribot, Janice A Royds, Sunali Mehta, Antony W Braithwaite, Noelyn A Hung, Tania L Slatter","doi":"10.1093/carcin/bgaf051","DOIUrl":"https://doi.org/10.1093/carcin/bgaf051","url":null,"abstract":"Tumour protein 53 (TP53) acts as a tumour suppressor and is often mutated in cancer. Isoforms of TP53, such as the Δ133p53 family, can promote tumour growth and metastasis. Therefore, targeting Δ133p53 function may represent a new strategy for preventing tumour metastasis. To inform the identification of proteins to target in Δ133p53-expressing tumours, changes at the cell surface were characterised. Inhibition of cell surface trafficking in a mouse model syngrafted with tumours expressing proteins similar to Δ133p53 (Δ122p53) was associated with reduced tumour growth and metastasis. After confirming that changes at the cell surface were important for Δ133p53 tumour promotion, characterisation of protein changes at the Δ133p53/Δ122p53 cell surface revealed increased expression of the toll-like receptor 4 (TLR4) and the TLR4 agonist, apoptosis inhibitor 5. Furthermore, inhibition of TLR4 was sufficient to reduce Δ122p53 tumour growth. Altogether, these results suggest a role for Δ133p53 in contributing to tumour progression by stimulating TLR4 function. Furthermore, targeting changes at the cell surface can reduce Δ133p53 tumour promotion.","PeriodicalId":9446,"journal":{"name":"Carcinogenesis","volume":" ","pages":""},"PeriodicalIF":2.9,"publicationDate":"2025-08-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144943957","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Associations of Pre-diagnostic Serum Liver Enzyme Levels with Lung Cancer Risk in Predominantly Low-income African and European Americans. 诊断前血清肝酶水平与主要低收入非洲和欧洲裔美国人肺癌风险的关系

IF 2.9 3区医学

Carcinogenesis Pub Date : 2025-08-29 DOI: 10.1093/carcin/bgaf052

Shuai Xu, Hui Cai, Jie Wu, Jiajun Shi, Regina Courtney, Hyung-Suk Yoon, Xiao-Ou Shu, William J Blot, Wei Zheng, Qiuyin Cai

{"title":"Associations of Pre-diagnostic Serum Liver Enzyme Levels with Lung Cancer Risk in Predominantly Low-income African and European Americans.","authors":"Shuai Xu, Hui Cai, Jie Wu, Jiajun Shi, Regina Courtney, Hyung-Suk Yoon, Xiao-Ou Shu, William J Blot, Wei Zheng, Qiuyin Cai","doi":"10.1093/carcin/bgaf052","DOIUrl":"https://doi.org/10.1093/carcin/bgaf052","url":null,"abstract":"Previous studies have linked liver diseases to lung cancer (LC) risk; however, few studies evaluated the associations of circulating liver enzyme levels with LC risk. We conducted a study of 353 incident LC cases and 646 matched controls with baseline serum alanine aminotransferase (ALT) and of 552 cases and 1039 matched controls with baseline serum alkaline phosphatase (ALP) nested within the Southern Community Cohort Study. Conditional logistic regression and generalized linear models were used to estimate adjusted odds ratios (ORs) and 95% confidence intervals (CIs) among all study participants and by stratification of potential effect modifiers. Most participants had clinically normal liver enzyme levels. Higher serum ALT levels were associated with reduced LC risk. Compared with the lowest tertile, participants in the second and third tertiles had OR (95% CI) of 0.74 (0.48-1.14) and 0.47 (0.28-0.78) (Ptrend < 0.01), respectively. The inverse association was observed in African Americans (AAs) and European Americans, which was especially prominent among men, and was seen in both those diagnosed within [ORT3 vs T1 =0.41 (0.19-0.88)] and beyond [ORT3 vs T1 = 0.35 (0.17-0.73)] a median follow-up time of 39 months. Higher serum ALP levels were associated with increased LC risk among AA men only [ORT3 vs T1 = 2.01 (1.19-3.39)] (Ptrend <0.01). Our results indicate that in a predominantly low-income American population, higher serum ALT levels may be related to lower LC risk. Further studies are warranted to confirm our findings and elucidate the potential underlying biological mechanisms of the associations.","PeriodicalId":9446,"journal":{"name":"Carcinogenesis","volume":" ","pages":""},"PeriodicalIF":2.9,"publicationDate":"2025-08-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144943961","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0