Risk Of Squamous Cell Carcinoma Research Articles

The analysis of Survivin promoter (−31G/C) gene variation in oral squamous cell carcinoma risk and prognosis

Background/aimOral squamous cell carcinoma (OSCC) is a malign tumor that associated with smoking and alcohol consumption, eating habits, environmental factors, and genetic susceptibility of the individuals. The Survivin gene, also known as BIRC5, plays important roles in the regulation of the cell cycle and apoptosis. The aim of the present study is to investigate Survivin -31G/C polymorphism in OSCC development and prognosis. Materials and methodsA total of 61 patients with oral squamous cell carcinoma and 133 healthy individuals were genotyped by using the Polymerase Chain Reaction-Restriction Fragment Length Polymorphism method (PCR-RFLP) to evaluate the role of the Survivin gene promoter region (-31) variation. ResultsThere were no statistically significant differences in the distribution of Survivin promoter -31 polymorphism genotype and allele frequencies between the cases and controls but we analyzed the clinicopathological characteristics of patients and noticed a significant correlation between the C allele and advanced tumor stage in the patients (p = 0.022). ConclusionThe Survivin (-31) gene polymorphism might be associated with advanced tumor stage in oral squamous cell carcinoma but further studies in a larger population are needed most effective evaluation of the Survivin (-31) gene variation in the OSCC risk and prognosis.

Common variants of pro-inflammatory gene IL1B and interactions with PPP1R13L and POLR1G in relation to lung cancer among Northeast Chinese

Lung cancer is a complex disease influenced by a variety of genetic and environmental factors. The cytokine interleukin 1 encoded by IL1B is an important mediator of the inflammatory response, and is involved in a variety of cellular activities. The effect of single nucleotide polymorphisms (SNP) at IL1B has been investigated in relation to cancer with inconsistent results. This Northeastern-Chinese case–control study involving 627 cases and 633 controls evaluated the role of three haplotype-tagging single nucleotide polymorphisms (htSNP) (rs1143633, rs3136558 and rs1143630) representing 95% of the common haplotype diversity across the IL1B gene and assessed interactions with IL1B, PPP1R13L, POLR1G and smoking duration in relation to lung cancer risk. The analyses of five genetic models showed associations with lung cancer risk for rs1143633 in the dominant model [adjusted-OR (95% CI) = 0.67 (0.52–0.85), P = 0.0012] and rs3136558 in the recessive model [adjusted-OR (95% CI) = 1.44 (1.05–1.98), P = 0.025]. Haplotype4 was associated with increased lung cancer risk [adjusted-OR (95% CI) = 1.55 (1.07–2.24), P = 0.021]. The variant G-allele of rs1143633 was protective in smoking sub-group of > 20 years. Using multifactor dimensionality reduction (MDR) analyses, we identified the three best candidate models of interactions and smoking-duration or IL1B rs1143633 as main effect. In conclusion, our findings suggest that IL1B SNP rs1143633 may associate with lower risk of lung cancer, confirming previously identified marker; IL1B SNP rs3136558 and haplotype4 consisting of IL1B htSNPs may associate with increasing risk of lung cancer; interactions of IL1B with POLR1G or PPP1R13L or smoking-duration, which is independent or combined, may involve in risk of lung cancer and lung squamous cell carcinoma.

Oral Cavity Squamous Cell Carcinoma Risk Factors: State of the Art.

Head and neck (HN) squamous cell carcinomas (SCCs) originate from the epithelial cells of the mucosal linings of the upper aerodigestive tract, which includes the oral cavity, the pharynx, the larynx, and the sinonasal cavities. There are many associated risk factors, including alcohol drinking coupled with tobacco use, which accounts for 70% to 80% of HNSCCs. Human papilloma virus (HPV) is another independent risk factor for oropharyngeal SCC, but it is only a minor contributor to oral cavity SCC (OSCC). Betel quid chewing is also an established risk factor in southeast Asian countries. However, OSCC, and especially oral tongue cancer, incidence has been reported to be increasing in several countries, suggesting risk factors that have not been identified yet. This review summarizes the established risk factors for oral cavity squamous cell carcinomas and examines other undemonstrated risk factors for HNSCC.

A subregion-based prediction model for local–regional recurrence risk in head and neck squamous cell carcinoma

Background and purposeGiven that the intratumoral heterogeneity of head and neck squamous cell carcinoma may be related to the local control rate of radiotherapy, the aim of this study was to construct a subregion-based model that can predict the risk of local–regional recurrence, and to quantitatively assess the relative contribution of subregions. Materials and methodsThe CT images, PET images, dose images and GTVs of 228 patients with head and neck squamous cell carcinoma from four different institutions of the The Cancer Imaging Archive(TCIA) were included in the study. Using a supervoxel segmentation algorithm called maskSLIC to generate individual-level subregions. After extracting 1781 radiomics and 1767 dosiomics features from subregions, an attention-based multiple instance risk prediction model (MIR) was established. The GTV model was developed based on the whole tumour area and was used to compare the prediction performance with the MIR model. Furthermore, the MIR-Clinical model was constructed by integrating the MIR model with clinical factors. Subregional analysis was carried out through the Wilcoxon test to find the differential radiomic features between the highest and lowest weighted subregions. ResultsCompared with the GTV model, the C-index of MIR model was significantly increased from 0.624 to 0.721(Wilcoxon test, p value < 0.0001). When MIR model was combined with clinical factors, the C-index was further increased to 0.766. Subregional analysis showed that for LR patients, the top three differential radiomic features between the highest and lowest weighted subregions were GLRLM_ShortRunHighGrayLevelEmphasis, GRLM_HghGrayLevelRunEmphasis and GLRLM_LongRunHighGrayLevelEmphasis. ConclusionThis study developed a subregion-based model that can predict the risk of local–regional recurrence and quantitatively assess relevant subregions, which may provide technical support for the precision radiotherapy in head and neck squamous cell carcinoma.

Risk of Squamous Cell Carcinoma of the Breast Following Postmastectomy Implant Reconstruction in Women With Breast Cancer and Carcinoma in Situ

This cohort study uses national surveillance data to describe the incidence and risk of squamous cell carcinoma after postmastectomy implant reconstruction in women with breast cancer.

Association of interleukin-10 rs1800896, rs1800872, and interleukin-6 rs1800795 polymorphisms with squamous cell carcinoma risk: A meta-analysis.

The relationship between interleukin (IL)-10 and IL-6 gene polymorphisms and squamous cell carcinoma (SCC) has been demonstrated but with inconsistent conclusions. The aim of this study was to evaluate the potential associations of IL gene polymorphisms and the SCC risk. PubMed, Cochrane Library, Web of Science, China National Knowledge Infrastructure, China Biomedical Database, WanFang, and China Science and Technology Journal Database databases were searched for articles reporting the correlations of IL-10 and IL-6 gene polymorphisms with the SCC risk. Odds ratio and 95% confidence interval were calculated using Stata Version 11.2. Meta-regression, sensitivity, and publication bias were analyzed. False-positive reporting probability and Bayesian measure of the false-discovery probability were used to explore the credibility of the calculation. Twenty-three articles were included. The IL-10 rs1800872 polymorphism showed a significant correlation with the SCC risk in the overall analysis. Studies pooled by ethnicity revealed that the IL-10 rs1800872 polymorphism reduced the SCC risk in the Caucasian population. The results of this study suggest that the IL-10 rs1800872 polymorphism may confer a genetic susceptibility to SCC, particularly oral SCC, in Caucasians. However, the IL-10 rs1800896 or IL-6 rs1800795 polymorphism was not significantly associated with the SCC risk.

A variant in CYP26B1 associated with esophageal squamous cell carcinoma risk by affecting retinoic acid metabolism.

All-trans retinoic acid (ATRA) is the natural and synthetic analogue of vitamin A, playing an essential tumor suppressive role in multiple cancers including the esophageal squamous cell carcinoma (ESCC). Cytochrome P450 family 26 subfamily B member 1 (CYP26B1) exerts a critical regulator of ATRA levels through specific inactivation of ATRA to hydroxylated forms. Our previous exome-wide analyses revealed a rare missense variant in CYP26B1 significantly associated with ESCC risk in the Chinese population. However, it is still unclear whether there are common variants in CYP26B1 affect the susceptibility of ESCC and the tumor promotion role of CYP26B1 in vivo. In this research, we conducted a two-stage case-control study comprised of 5057 ESCC cases and 5397 controls, followed by a series of biochemical experiments to explore the function of CYP26B1 and its common variants in the tumorigenesis of ESCC. Intriguingly, we identified a missense variant rs2241057[A>G] in the fourth exon of CYP26B1 significantly associated with the ESCC risk (combined odds ratio = 1.28; 95% confidence interval = 1.15-1.42; p = 2.96 × 10-6 ). Through further functional analysis, we demonstrated that ESCC cells with the overexpression of rs2241057[G] had a significant lower level of retinoic acid, compared with the overexpression of rs2241057[A] or the control vector. In addition, the CYP26B1 overexpression and knock-out ESCC cells affected cell proliferation rate both in vitro and in vivo. These results highlighted the carcinogenicity of CYP26B1 related to the ATRA metabolism in ESCC risk.

Association between idiopathic pulmonary fibrosis and risk of different pathological types of lung cancer: a Mendelian randomization study.

Many epidemiological studies have shown that idiopathic pulmonary fibrosis (IPF) is a risk factor for lung cancer (LC), but these studies do not provide direct evidence of a causal association between the two diseases. We investigated the causal association between IPF and different pathological types of LC based on the Mendelian randomization (MR) study. The genome-wide association study (GWAS) data of IPF and LC were obtained from the latest published articles, and instrumental variables (IVs) for analysis were obtained after screening and eliminating the confounders. MR Analysis was carried out with the help of random effects inverse variance weighting (re-IVW), MR-egger, and weighted median method, and a comprehensive sensitivity test was conducted. The results of re-IVW analysis showed that IPF may increase the risk of lung squamous cell carcinoma (LUSC) (OR = 1.045, 95% CI 1.011 to 1.080, P = 0.008). In addition, no causal relationship was found between IPF and overall LC (OR = 0.977, 95% CI 0.933 to 1.023, P = 0.32), lung adenocarcinoma (LUAD) (OR = 0.967, 95% CI 0.903 to 1.036, P = 0.345) and small cell lung carcinoma (SCLC) (OR = 1.081, 95% CI 0.992 to 1.177, P = 0.074). A comprehensive sensitivity analysis ensured the reliability of the study. In conclusion, from the perspective of genetic association, we found that IPF is an independent risk factor for LUSC and may increase the risk of LUSC, but no such causal relationship was found in LUAD and SCLC.

Effect of CDH1 and CDH2 genes polymorphisms in oral squamous cell carcinoma susceptibility in a sample of Iranian population: A case-control study.

Oral squamous cell carcinoma (OSCC) is a global malignant epithelial neoplasm affecting the oral cavity. Cadherins, as an adhesion molecule, are involved in cell-cell interaction. We aim to study the effect of two cadherin polymorphisms on OSCC risk in southeast of Iran. In this case-control study, 94 individuals (47 OSCC cases and 47 controls), that referred to the Department of Oral Pathology, Faculty of Dentistry, Zahedan University of Medical Sciences, Iran were included. Cadherin single nucleotide polymorphisms CDH1 (rs16260) and CDH2 (rs11564299) were genotyped by the tetra-Amplification Refractory Mutation System-PCR technique. N-cadherin genotyping showed that the AA, AG, and AG + GG were presented 78.7%, 17%, 21.3% versus 66%, 29.7%, 34% in the cases and the control group, respectively. AG genotype was more common in control than case (OR = 0.47, 95% CI: 0.17-1.29, p = 0.14). G allele was more prevalent in control (19.1%) than the case group (12.8%) (OR = 0.61, 95% CI: 0.27-1.36, p = 0.23). In E-cadherin, AC, AA, and AC + AA genotypes frequency were 17%, 12.8%, and 29.8% in case versus 8.5%, 8.5%, and 17% in the control group. Allele A was more common in the case than the control group (OR = 1.84, 95% CI: 0.84-4.03, p = 0.12). Also, AA and CC, the codominant genotypes were common in CDH2 and CDH1 respectively in all histopathological grades, and no statically significant association was observed between OSCC different histopathological grades and cadherin genotypes (p = 0.39 in N-cadherin, p = 0.74 in E-cadherin). Our results showed a lack of association between CDH1 and CDH2 gene polymorphisms with OSCC risk in a population of Southeastern of Iran.

The effect of statin medication on the incidence of oral squamous cell carcinoma among betel-nut chewers.

This study examines the relationship between statin use and oral cancer squamous cell carcinoma (OCSCC) risk in a cohort of 47 942 betel nut chewers. The study used individual 1:1 matching and propensity score matching to compare statin users and nonusers. The incidence rate of OCSCC was significantly lower in statin users compared to nonusers (17.12 vs. 26.75 per 10 000 person-years), yielding an incidence rate ratio of 0.64. After adjusting for confounders, statin use was associated with a reduced risk of OCSCC (adjusted hazard ratio: 0.61; 95% confidence interval: 0.52-0.71). A dose-response relationship was observed, with a significant reduction in OCSCC incidence when the cumulative defined daily dose of statin use was equal to or greater than Q3. The risk of OCSCC was lower among users of both hydrophilic and lipophilic statins. This study provides evidence that statin use is associated with a reduced risk of OCSCC in betel nut chewers.

Early Diagnosis of Oral Cancer and Lesions in Fanconi Anemia Patients: A Prospective and Longitudinal Study Using Saliva and Plasma.

Fanconi anemia (FA) patients display an exacerbated risk of oral squamous cell carcinoma (OSCC) and oral potentially malignant lesions (OPMLs) at early ages. As patients have defects in their DNA repair mechanisms, standard-of-care treatments for OSCC such as radiotherapy and chemotherapy, give rise to severe toxicities. New methods for early diagnosis are urgently needed to allow for treatment in early disease stages and achieve better clinical outcomes. We conducted a prospective, longitudinal study wherein liquid biopsies from sixteen patients with no clinical diagnoses of OPML and/or OSCC were analyzed for the presence of mutations in cancer genes. The DNA from saliva and plasma were sequentially collected and deep-sequenced, and the clinical evaluation followed over a median time of approximately 2 years. In 9/16 FA patients, we detected mutations in cancer genes (mainly TP53) with minor allele frequencies (MAF) of down to 0.07%. Importantly, all patients that had mutations and clinical follow-up data after mutation detection (n = 6) developed oral precursor lesions or OSCC. The lead-time between mutation detection and tumor diagnosis ranged from 23 to 630 days. Strikingly, FA patients without mutations displayed a significantly lower risk of developing precursor lesions or OSCCs. Therefore, our diagnostic approach could help to stratify FA patients into risk groups, which would allow for closer surveillance for OSCCs or precursor lesions.

Tumour Necrosis Factor Alpha (TNF-α) and Oral Squamous Cell Carcinoma.

Uncovering the inflammatory mechanisms underpinning initiation, progression, and promotion of oral squamous cell carcinoma (OSCC) development is fundamental to the rational pursuit of targeted therapeutics. Here we present a review of the current knowledge of the role of TNF-α in the aetiology, pathogenesis, and potential therapies with regards to OSCC. TNF-α is worthy of particular attention in OSCC, with its presence demonstrated to enhance cell proliferation and its downregulation demonstrated to inhibit proliferation and migration in other carcinomas in both in vitro and in vivo models and oral cancer patients. Increased TNF-α in the OSCC tumour microenvironment has been demonstrated to favour invasion through promotion of firstly the pro-inflammatory, pro-invasive phenotypes of OSCC cells and secondly its paracrine mechanism mediating recruitment and activation of inflammatory cells. Polymorphisms affecting the gene expression of TNF-α have been strongly associated with an increased risk for oral squamous cell carcinoma. A number of studies have considered TNF-α within biofluids, including saliva and serum, as a potential biomarker for the early detection of OSCC, as well as its staging, differentiation, and prognosis. The broad and multifaceted role that TNF-α plays in many inflammatory states presents an obvious confounder, particularly with demonstrated increased TNF-α levels in common oral disease states. Lastly, biologic agents targeting TNF-α are currently in clinical use for immune-mediated inflammatory rheumatological and gastrointestinal diseases. There is the potential that these biological agents might have an adjunctive role in OSCC prevention and treatment.

Risk of cutaneous squamous cell carcinoma due to occupational exposure to solar ultraviolet radiation: Protocol for a systematic review and meta-analysis.

Solar ultraviolet radiation (UVR) is the most significant occupational carcinogenic exposure in terms of the number of workers exposed (i.e., outdoor workers). Consequently, solar UVR-induced skin cancers are among the most common forms of occupational malignancies that are potentially expected globally. This systematic review is registered in PROSPERO (CRD42021295221) and aims to assess the risk of cutaneous squamous cell carcinoma (cSCC) associated to occupational solar UVR exposure. Systematic searches will be performed in three electronic literature databases (PubMed/Medline, EMBASE, and Scopus). Further references will be retrieved by a manual search (e.g., in grey literature databases, internet search engines, and organizational websites). We will include cohort studies and case-control studies. Risk of Bias assessment will be conducted separately for case-control and cohort studies. The Grading of Recommendations Assessment, Development, and Evaluation (GRADE) will be used for the certainty of assessment. In case quantitative pooling is not feasible, a narrative synthesis of results will be performed.

Compromised T Cell Immunity Links Increased Cutaneous Papillomavirus Activity to Squamous Cell Carcinoma Risk.

Cutaneous squamous cell carcinoma (cSCC) is the second most common cancer, with increased incidence in immunosuppressed patients. β-Human papillomavirus has been proposed as a contributor to cSCC risk partly on the basis of increased β-human papillomavirus viral load and seropositivity observed among patients with cSCC. Experimental data in mice colonized with mouse papillomavirus type 1 suggest that T cell immunity against β-human papillomavirus suppresses skin cancer in immunocompetent hosts, and the loss of this immunity leads to the increased risk of cSCC. In this study, we show that CD8+ T cell depletion in mouse papillomavirus type 1‒colonized mice that underwent skin carcinogenesis protocol led to increased viral load in the skin and seropositivity for anti‒mouse papillomavirus type 1 antibodies. These findings provide evidence that compromised T cell immunity can be the link that connects increased β-human papillomavirus detection to cSCC risk.

Utility of mono-exponential, bi-exponential, and stretched exponential signal models of intravoxel incoherent motion (IVIM) to predict prognosis and survival risk in laryngeal and hypopharyngeal squamous cell carcinoma (LHSCC) patients after chemoradiotherapy

PurposeTo investigate the predictive power of mono-exponential, bi-exponential, and stretched exponential signal models of intravoxel incoherent motion (IVIM) in prognosis and survival risk of laryngeal and hypopharyngeal squamous cell carcinoma (LHSCC) patients after chemoradiotherapy.Materials and methodsForty-five patients with laryngeal or hypopharyngeal squamous cell carcinoma were retrospectively enrolled. All patients had undergone pretreatment IVIM examination, subsequently, mean apparent diffusion coefficient (ADCmean), maximum ADC (ADCmax), minimum ADC (ADCmin) and ADCrange (ADCmax − ADCmean) by mono-exponential model, true diffusion coefficient (D), pseudo diffusion coefficient (D*), perfusion fraction (f) by bi-exponential model, distributed diffusion coefficient (DDC), and diffusion heterogeneity index (α) by stretched exponential model were measured. Survival data were collected for 5 years.ResultsThirty-one cases were in the treatment failure group and fourteen cases were in the local control group. Significantly lower ADCmean, ADCmax, ADCmin, D, f, and higher D* values were observed in the treatment failure group than in the local control group (p < 0.05). D* had the greatest AUC of 0.802, with sensitivity and specificity of 77.4 and 85.7% when D* was 38.85 × 10–3 mm2/s. Kaplan–Meier survival analysis showed that the curves of N stage, ADCmean, ADCmax, ADCmin, D, D*, f, DDC, and α values were significant. Multivariate Cox regression analysis showed ADCmean and D* were independently correlated with progression-free survival (PFS) (hazard ratio [HR] = 0.125, p = 0.001; HR = 1.008, p = 0.002, respectively).ConclusionThe pretreatment parameters of mono-exponential and bi-exponential models were significantly correlated with prognosis of LHSCC, ADCmean and D* values were independent factors for survival risk prediction.

Significant Association of Poly-A and Fok1 Polymorphic Alleles of the Vitamin D Receptor with Vitamin D Serum Levels and Incidence of Squamous Cutaneous Neoplasia

Vitamin D3, a prohormone, is converted to circulating calcidiol and then to calcitriol, the hormone that binds to the vitamin D receptor (VDR) (a nuclear transcription factor). Polymorphic genetic sequence variants of the VDR are associated with an increased risk of breast cancer and melanoma. However, the relationship between VDR allelic variants and the risk of squamous cell carcinoma and actinic keratosis remains unclear. We examined the associations between two VDR polymorphic sites, Fok1 and Poly-A, and serum calcidiol levels, actinic keratosis lesion incidence, and the history of cutaneous squamous cell carcinoma in 137 serially enrolled patients. By evaluating the Fok1 (F) and (f) alleles and the Poly-A long (L) and short (S) alleles together, a strong association between genotypes FFSS or FfSS and high calcidiol serum levels (50.0 ng/ml) was found; conversely, ffLL patients showed very low calcidiol levels (29.1 ng/ml). Interestingly, the FFSS and FfSS genotypes were also associated with reduced actinic keratosis incidence. For Poly-A, additive modeling showed that Poly-A (L) is a risk allele for squamous cell carcinoma, with an OR of 1.55 per copy of the L allele. We conclude that actinic keratosis and squamous cell carcinoma should be added to the list of squamous neoplasias that are differentially regulated by the VDR Poly-A allele.

Association of Antihistamine Use with Increased Risk of Esophageal Squamous Cell Carcinoma: A Nationwide, Long-Term Follow-Up Study Using Propensity Score Matching.

To examine the association between H1-antihistamines (AHs) use and the incidence of esophageal squamous cell carcinoma (ESCC) in a head-to-head propensity score matching (PSM) comparative study. Retrospective cohort study. Nationwide population-based study in Taiwan. 1289,526 adults from the National Health Insurance Research Database from 2008 to 2018. AH use. Incidence rates (IRs), incidence rate ratios (IRRs), and adjusted hazard ratios (aHRs) of ESCC in AH users compared with nonusers. AH users had a significantly higher IR of ESCC than nonusers (1.47 vs. 1.36 per 100,000 person-years). The IRR (95% CI) for ESCC was 1.18 (1.08-1.28) in AH users compared with nonusers. After adjustment for age, sex, income levels, urbanization, cigarettes smoking, alcoholic related diseases, comorbidities, medication use, and Charlson Comorbidity Index scores, the aHR (95% CI) for ESCC was 1.22 (1.12-1.33) in AH users compared with nonusers. A dose-response relationship was also observed, with aHRs for AH use at 28-182, 183-488, 489-1043, and >1043 cumulative defined daily doses (cDDDs) of 1.12, 1.20, 1.25, and 1.37, respectively, compared with <28 cDDDs. Our study found a significant association between AH use and the increased risk of ESCC, with a dose-response relationship. This study suggests that AH use may increase the risk of ESCC, especially at high doses, and highlights the importance of caution when prescribing AHs.

Association between tonsillectomy and oropharyngeal cancer risk: a retrospective cohort study.

The purpose of this retrospective cohort study is to describe the association between the history of tonsillectomy and the risk of oropharyngeal squamous cell carcinoma (OPSSC), using a large cohort of patients. We performed a retrospective cohort study with 3620 patients diagnosed with OPٍSCC from 2010 to 2021. We utilized the University of Florida patients' registry i2b2 system. Three subsets of OPSSC were defined, base of tongue(BOT) cancer, tonsillar cancer, and other OPSSC. Tumor demographics and history of tonsillectomy were collected. Odds ratio for OPSSC were assessed utilizing a logistic regression model with adjusting for gender, race, and age.P < 0.05 was deemed significant. Of the 3620 OPSSC patients were BOT cancer (N = 964), tonsillar cancer (N = 995), and other OPSSC (N = 1661). There was a statistically significant reduction in tonsillar cancer and BOT cancer odds ratio in patients with a history of tonsillectomy vs. patients without tonsillectomy(0.086 and 0.117), respectively, with a P value < .0001. The odds ratio of OPSSC in patients with a history of tonsillectomy vs. patients without tonsillectomyis 1.031. This study showed that the OPSSC and previous history of tonsillectomy are associated. Our results showed a significant reduction in BOT and tonsillar cancer risk in patients with a history of tonsillectomy and an insignificant decrease in other OPSSC. This study could emphasize the importance of the development of future clinical trials to investigate the role of prophylactic tonsillectomy as a secondary preventive strategy to reduce OPSSC.

Association of LAMA1 Single-Nucleotide Polymorphisms with Risk of Esophageal Squamous Cell Carcinoma among the Eastern Chinese Population.

LAMA1, also known as laminin subunit α1, is a member of the laminin family, which is widely reported to be a key basement membrane molecule that affects various biological activities and is associated with many kinds of diseases. We aimed to investigate the association between LAMA1single-nucleotide polymorphisms and the occurrence and progression of esophageal squamous cell carcinoma in the Chinese population. 2,186 participants were collected retrospectively between October 2008 and January 2017, including 1,043 ESCC patients and 1,143 noncancer patients. A 2 mL blood sample was obtained intravenously for the LDR for SNP analysis. The 6 SNP loci of LAMA1 were selected and examined. We analyzed the association of several genetic models of 6 LAMA1 SNP loci, sex, age, smoking and drinking status, and the occurrence of esophageal squamous cell carcinoma. In the rs62081531 G > A locus, genotype GA was a protective factor for ESCC compared with GG (OR: 0.830, P=0.046), especially among the younger and nondrinkers. At rs607230 T > C, genotype TC was linked with a lower risk of ESCC compared with TT. (OR: 0.613, P=0.034). Haplotype Frequencies revealed that Ars62081531Grs621993Ars539713Trs566655Ars73938538Crs607230 (OR: 0.803, P=0.028) and Grs62081531Grs621993Ars539713Trs566655Crs73938538Crs607230 (OR: 0.679, P=0.010) were strongly associated with lower susceptibility of ESCC. The LAMA1 rs62081531, rs539713, rs566655, and rs607230 polymorphisms were demonstrated to be related to susceptibility to ESCC in the Chinese population. LAMA1 SNPs may have a significant impact on the occurrence of esophageal cancer and may serve as potential diagnostic biomarkers.

Common inherited variants of PDCD1, CD274 and HAVCR2 genes differentially modulate the risk and prognosis of adenocarcinoma and squamous cell carcinoma

BackgroundTo investigate the association between single nucleotide polymorphisms (SNPs) of PDCD1, CD274, and HAVCR2 genes with the risk and outcomes of non-small cell lung cancer (NSCLC) subtypes: squamous cell lung cancer (LUSC) and lung adenocarcinoma (LUAD).MethodsTaqMan SNP genotyping assays or polymerase chain reaction-restriction fragment length polymorphism methods were used to determine genotypes of: PDCD1: rs36084323, rs7421861, rs11568821, rs2227981, rs10204525; CD274: rs822335, rs10815225, rs17718883, rs2297136, rs4742098, rs4143815; HAVCR2: rs10057302, rs1036199. Among 383 NSCLC patients, 112 were diagnosed with LUAD and 116 with LUSC. The control group consisted of 433 unrelated, cancer-free subjects.ResultsA CC genotype of rs4143815 and GG genotype of rs4742098 were associated with two times higher risk of developing LUSC (CC vs. GG + GC, OR = 2.31; 95% CI = 1.32, 4.06; P = 0.003; GG vs. AA + AG, OR = 2.26; 95% CI = 1.17, 4.36; P = 0.016, respectively). Moreover, rs4143815 was an independent predictor of the age at diagnosis of LUAD. The carriers of C allele were diagnosed 4.81 years later (95% CI = 1.47, 8.15; P = 0.006) than patients with the GG genotype. The rs10057302 CA genotype was an independent predictor of overall survival in LUSC (adjusted HR = 0.13; 95% CI = 0.02, 0.93; P = 0.043). NSCLC carriers of rs11568821 T allele had almost double the risk of death (adjusted HR = 2.05; 95% CI = 1.28, 3.29; P = 0.003) compared to carriers of CC genotype.ConclusionsOur results provided additional evidence that SNPs of genes for PD-1, PD-L1 and TIM-3 differentially modulate the risk and prognosis of LUSC and LUAD.