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Esophageal squamous cell carcinoma （ESCC） is a malignant tumor caused by both environmental and genetic factors. Epidemiology studies have identified smoking as a major environmental risk factor. In recent years， the advancement of genomics research has led to the recognition of the influence of genetic variation in ESCC. We reviewed the research progress in smoking， genetic polymorphism and their interaction on susceptibility to ESCC. Reducing exposure time to tobacco was found to be the most effective way to reduce the risk. At the genetic level， mutations in DNA repair genes， regulation genes of carcinogen-metabolizing enzymes， cell cycle regulation genes， folate metabolism related genes， and alcohol metabolism related genes were found to significantly increase the risk of ESCC. However， studies on the interaction between smoking and genetic polymorphisms in ESCC risk are still limited， more studies are needed for better screening of the high-risk populations and the prevention.
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Esophageal squamous cell carcinoma （ESCC） is a malignant tumor caused by both environmental and genetic factors. Epidemiology studies have identified smoking as a major environmental risk factor. In recent years， the advancement of genomics research has led to the recognition of the influence of genetic variation in ESCC. We reviewed the research progress in smoking， genetic polymorphism and their interaction on susceptibility to ESCC. Reducing exposure time to tobacco was found to be the most effective way to reduce the risk. At the genetic level， mutations in DNA repair genes， regulation genes of carcinogen-metabolizing enzymes， cell cycle regulation genes， folate metabolism related genes， and alcohol metabolism related genes were found to significantly increase the risk of ESCC. However， studies on the interaction between smoking and genetic polymorphisms in ESCC risk are still limited， more studies are needed for better screening of the high-risk populations and the prevention.
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Multi-factor research design is widely applied in scientific research. It can simultaneously explore the effects of multiple factors on outcome indicators. The consideration of the interactive effects of different factors is a critical issue when analyzing this type of data. The analytic strategy for main effects or simple effects depends on the significance of the interactive effect. However, many researchers tend to skip the analysis on interactive effects, or wrongly select statistical analysis method because of ignoring the test result. In this study, SPSS 20.0 and R 3.6.1 statistical software were used to simulate and illustrate how to analyze data from two most popular multi-factor design data——factorial design and repeated measurement design. The significance of evaluating interactive effect and corresponding key point analysis was explained. The possible consequences of ignoring the statistical significance of interactive effects were indicated, that include leading to low inspection efficiency, prone to draw wrong conclusions, loss of valuable information in the original data, or loss of practical significance of the analytic results. It is suggested that in the analysis of research data, we should first judge whether there are interactive effects, and then correctly choose main effect analysis or single effect analysis to avoid one-sided and wrong conclusions.
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Objective@#To investigate the role of human papillomavirus (HPV) 16 early genes E2 and E6 and heterogeneous nuclear ribonucleoprotein (hnRNP) E2 and their interaction effects in the progression of the cervical cancer.@*Methods@#Women with normal cervix (NC), low cervical intraepithelial neoplasia (CIN Ⅰ) and high cervical intraepithelial neoplasia (CIN Ⅱ/Ⅲ) from the cervical lesions cohort in Jiexiu County of Shanxi Province from June 2014 to September 2014, and patients with cervical squamous cell carcinoma (SCC) treated at the Second Hospital of Shanxi Medical University in the same period were enrolled in this study. There were 257 participants, about 67 NC cases (26.07%), 69 CIN Ⅰ cases (26.85%), 68 CIN Ⅱ/Ⅲ cases (26.46%), and 53 SCC cases (20.62%), respectively. The information of demographic characteristics, life health habits and cervical lesions were collected by using the structured questionnaire. Cervical exfoliated cells and cervical biopsy tissues were collected to detect the infection of HPV16 and the protein expression levels of hnRNP E2, HPV16 E2 and E6. According to the median-value of the protein expression levels of hnRNP E2, HPV16 E2 and E6 and E2/E6 ratio in the NC group, the study participants were divided into the high and low expression groups/ratio groups. The multivariate logistic regression model was used to analyze the correlation between HPV16 early gene E2 and E6, hnRNP E2 and cervical cancer. The interaction effect was analyzed by using the generalized multifactor dimensionality reduction (GMDR) model.@*Results@#The ages of NC, CIN Ⅰ, CIN Ⅱ/Ⅲ and SCC groups were (47.00±9.07), (47.64±7.35), (46.37±8.67) and (51.26±8.03) years old, respectively. The multivariate logistic regression model analysis showed that the HPV16 E2 low expression, E6 high expression and E2/E6 low ratio could increase the risk of CIN Ⅱ/Ⅲ, about OR (95%CI) values 11.11 (1.63-75.56), 8.00 (1.28-50.04), and 9.75 (1.22-77.72), respectively and SCC, about OR (95%CI) values 14.22 (2.11-95.88), 10.33 (1.67-64.00), and 12.38 (1.56-97.91), respectively. The hnRNP E2 low expression could increase the risk of CIN Ⅱ/Ⅲ and SCC, about OR (95%CI) values 3.35 (1.39-8.10) and 5.53 (1.54-19.88). The result of GMDR showed that there were interaction effects of the hnRNP E2 low expression, HPV16 E2 low expression and HPV16 E6 high expression in both CIN Ⅱ/Ⅲ and SCC groups.@*Conclusion@#The HPV16 E2 low expression, HPV16 E6 high expression and hnRNP E2 low expression could increase the risk of high-grade cervical intraepithelial neoplasia and cervical cancer, and they might have an important interaction effect in the progression of the cervical cancer.
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Objective: To investigate the modifying effect of maternal education level on the association between the number of prenatal care visits and neonatal low birth weight (LBW). Methods: The information about women of childbearing age and their children was obtained through a survey on the status of birth defects and their risk factors in Shaanxi Province. Logistic regression model was used to explore the multiplied interaction between maternal education level or the number of prenatal care visits and neonatal low birth weight and the Excel table prepared by Andresson et al. was used to calculate the adding interaction. Results: With the increase of the number of prenatal care visits, the incidence of LBW and SGA in all the newborns and full-term infants gradually decreased. When the mother's education level was high school and above, the risk of incidence of LBW (OR=0.81, 95% CI 0.65-1.00) and SGA (OR=0.86, 95% CI 0.77-0.95) in all the newborns and full-term infants (OR=0.76, 95% CI 0.60-0.97) were reduced. Also there was a reduced risk of LBW and SGA in all the newborns and full-term infants with increased times of prenatal care visits. Interaction analysis showed that the level of maternal education and the number of prenatal care visits only had multiplied interaction on LBW (OR=0.78, 95% CI: 0.63-0.97) and SGA (OR=0.84, 95% CI: 0.76-0.94) in all the newborns and full-term infants (OR=0.72, 95% CI: 1.11-1.25). Conclusion: The lower education level of the mother and fewer antenatal care visits were the risk factors for the occurrence of neonatal LBW, and the level of maternal education had a modifying effect on the influence of prenatal examination on neonatal LBW. Higher maternal education can improve the effect of fewer prenatal care visits on neonates' LBW.
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Objective To investigate the influencing factors for liver cancer by gender in Shunde region, and to explore the potential interactions among influencing factors for liver cancer in males. Methods The relative excess risk of interaction (RERI) and other indices were used to evaluate the pair-wise interaction, and the classification and regression tree (CART) model was applied to explore the potential multi-factors interaction. Results This study included 1 037 male cases and 1 069 controls, together with 166 female cases and 185 controls. Chronic hepatitis B virus infection (CHB) and family history of liver cancer were significantly associated with increased risk of liver cancer both in males and females (both P<0.001). In males, positive additive interactions were observed between CHB and smoking or alcohol drinking, as well as between smoking and drinking. The RERI for CHB and smoking was 121.90(95% CI：52.85%-190.95%). Negative additive interactions were observed between exercise and CHB or smoking. Further, the CART analysis suggested that the CHB males who smoked and drank alcohol had the highest risk of liver cancer. Conclusions CHB and family history of liver cancer are important risk factors for liver cancer in both males and females. CHB, smoking, and alcohol drinking synergistically promote the incidence of liver cancer for males. Exercise can antagonize the hepatocarcinogenic effect of CHB and smoking.
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OBJECTIVE: To evaluate the genetic damage induced by occupational chromate exposure, and to analyze the association between human 8-oxoguanine-DNA N-glycosylase 1(hOGG1) polymorphisms and genetic damage in population with chromate exposure. METHODS: A total of 136 chromate exposed workers were recruited as exposure group by judgmental sampling method, and 156 workers without chromate and other occupational hazard factors exposure were recruited as control group. The whole blood chromium(WB-Cr) level was measured by inductively coupled plasma mass spectrometry. Urinary 8-hydroxy-2′-deoxyguanosine(8-OHdG) was determined by enzyme-linked immunosorbent assay. Four single nucleotide polymorphisms of hOGG1 gene were genotyped by the matrix assisted laser desorption ionization/time of flight mass spectrometry. RESULTS: The WB-Cr level was higher in the exposure group than that in the control group(meclian: 3.41 vs 0.90 μg/L, P<0.01). The urinary 8-OHdG level was higher in the exposure group compared with that in the control group(meclian: 6.02 vs 4.72 μg/g·creatinine, P<0.01). In study subjects(exposure group and control group), after adjusting the potential influencing factors such as age, body mass index(BMI), gender, smoking and drinking, chromate exposure might be a risk factor for increasing urinary 8-OHdG level(P<0.05), and the recessive models of rs293796 and rs13096551 were observed as risk factors of increasing urinary 8-OHdG level(P<0.05). In chromate exposure group, the additive and recessive models of rs293796 and the recessive model of rs13096551 were observed as risk factors of increasing urinary 8-OHdG level(P<0.05), while the dominant model of rs3219008 was protective factor of increasing urinary 8-OHdG level(P<0.05), after adjusting the potential influencing factors such as age, BMI, gender, smoking, drinking. However, after multiple Bonferroni correction tests, only the recessive model of rs293796 was the risk factor of increasing urinary 8-OHdG level in the exposed group(P<0.01). There was significant interaction between chromate exposure and rs293796 on urinary 8-OHdG(P<0.01). CONCLUSION: The rs13096551 and rs293796 of hOGG1 were associated with the alteration of urinary 8-OHdG level induced by chromate. There was interaction between rs294796 of hOGG1 and chromate exposure on urinary 8-OHdG level.
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Objective To explore the SNP effects ofpatatin-like phospholipase domain which containing 3 (PNPLA3),transmembrane 6 superfamily member 2 (TM6SF2) gene,environmental effects of smoking,alcohol drinking and interaction between gene-gene,gene-environment and drinking-smoking on hepatitis B virus-associated hepatocellular carcinoma (HBV-HCC).Methods We collected anticoagulant peripheral blood from patients of HBV-HCC,chronic hepatitis B (CHB),liver cirrhosis (LC) and from healthy controls to detect the single nucleotide polymorphism (SNP) of patatin-like phospholipase domain containing 3 (PNPLA3) gene loci rs738409 and transmembrane 6 superfamily member 2 (TM6SF2) gene loci rs58542926,using the flight mass spectrometry method.The optimal assignment value of gene polymorphisms was defined by using the online SNP stats.Hardy-Weinberg (H-W) balance was tested for SNP.Effects of the genetic and environmental factors to HBV-HCC were analyzed by using the multiple classification logistic regression method.The gene-gene,gene-smoking and alcohol drinking interaction effects were investigated by Fork-Life analysis and binary logistic regression methods.Results The frequency distribution of CHB group rs738409 loci seemed not in conformity with the H-W balance (x2=11.980,P＜0.005).Two loci frequency distributions in the other groups were all in accordandce with the H-W balance.After adjusting for influences on age and sex and comparing to the healthy group,the rs58542926 mutation appeared as OR=1.659,95％CI:1.026-2.684,P=0.039,in the HBV-HCC group.When comparing to CHB group,the HBV-HCC group presented that drinking as OR=1.680,95％CI:1.121-2.519,P=0.012.When comparing to the LC group,the ORs of drinking and smoking were 1.539 (1.071-2.213) and 1.453 (1.005-2.099) respectively,in the HBV-HCC group.When comparing to the CHB + LC group,interactions between the HBV-HCC group were found rs738409 and rs58542926 on additive model OR=1.548 (U=1.885,P=0.029) and OR=1.658 (P=0.024) on logistic regression model while drinking was rs738409 on interaction additive model with OR=1.811(U=1.965,P=0.024).As for drinking and mutation of rs738409,the multiplication model of logistic regression showed no statistically significant differences.Interaction between smoking and drinking appeared as OR=1.756 (P＜0.001) in the logistics regression multiplication model.Conclusions Factors as mutation of TM6SF2,smoking and drinking all appeared as risk factors for HBV-HCC.Mutations of both PNPLA3 and TM6SF2,together with smoking and drinking all served as risk factors for HBV-HCC.However,the mutation of single PNPLA3 appeared as a protective factor on HBV-HCC.
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Objective To explore the SNP effects ofpatatin-like phospholipase domain which containing 3 (PNPLA3),transmembrane 6 superfamily member 2 (TM6SF2) gene,environmental effects of smoking,alcohol drinking and interaction between gene-gene,gene-environment and drinking-smoking on hepatitis B virus-associated hepatocellular carcinoma (HBV-HCC).Methods We collected anticoagulant peripheral blood from patients of HBV-HCC,chronic hepatitis B (CHB),liver cirrhosis (LC) and from healthy controls to detect the single nucleotide polymorphism (SNP) of patatin-like phospholipase domain containing 3 (PNPLA3) gene loci rs738409 and transmembrane 6 superfamily member 2 (TM6SF2) gene loci rs58542926,using the flight mass spectrometry method.The optimal assignment value of gene polymorphisms was defined by using the online SNP stats.Hardy-Weinberg (H-W) balance was tested for SNP.Effects of the genetic and environmental factors to HBV-HCC were analyzed by using the multiple classification logistic regression method.The gene-gene,gene-smoking and alcohol drinking interaction effects were investigated by Fork-Life analysis and binary logistic regression methods.Results The frequency distribution of CHB group rs738409 loci seemed not in conformity with the H-W balance (x2=11.980,P＜0.005).Two loci frequency distributions in the other groups were all in accordandce with the H-W balance.After adjusting for influences on age and sex and comparing to the healthy group,the rs58542926 mutation appeared as OR=1.659,95％CI:1.026-2.684,P=0.039,in the HBV-HCC group.When comparing to CHB group,the HBV-HCC group presented that drinking as OR=1.680,95％CI:1.121-2.519,P=0.012.When comparing to the LC group,the ORs of drinking and smoking were 1.539 (1.071-2.213) and 1.453 (1.005-2.099) respectively,in the HBV-HCC group.When comparing to the CHB + LC group,interactions between the HBV-HCC group were found rs738409 and rs58542926 on additive model OR=1.548 (U=1.885,P=0.029) and OR=1.658 (P=0.024) on logistic regression model while drinking was rs738409 on interaction additive model with OR=1.811(U=1.965,P=0.024).As for drinking and mutation of rs738409,the multiplication model of logistic regression showed no statistically significant differences.Interaction between smoking and drinking appeared as OR=1.756 (P＜0.001) in the logistics regression multiplication model.Conclusions Factors as mutation of TM6SF2,smoking and drinking all appeared as risk factors for HBV-HCC.Mutations of both PNPLA3 and TM6SF2,together with smoking and drinking all served as risk factors for HBV-HCC.However,the mutation of single PNPLA3 appeared as a protective factor on HBV-HCC.
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BACKGROUND/AIMS: Methylation status plays a causal role in carcinogenesis in targeted tissues. However, the relationship between the DNA methylation status of multiple genes in blood leukocytes and colorectal cancer (CRC) susceptibility as well as interactions between dietary factors and CRC risks are unclear. METHODS: We performed a case-control study with 466 CRC patients and 507 cancer-free controls to investigate the association among the methylation status of individual genes, multiple CpG site methylation (MCSM), multiple CpG site heterogeneous methylation and CRC susceptibility. Peripheral blood DNA methylation levels were detected by performing methylation-sensitive high-resolution melting. RESULTS: Total heterogeneous methylation of CA10 and WT1 conferred a significantly higher risk of CRC (adjusted odds ratio [OR(adjusted)], 5.445; 95% confidence interval [CI], 3.075 to 9.643; OR(adjusted), 1.831; 95% CI, 1.100 to 3.047; respectively). Subjects with high-level MCSM (MCSM-H) status demonstrated a higher risk of CRC (OR(adjusted), 4.318; 95% CI, 1.529 to 12.197). Additionally, interactions between the high-level intake of fruit and CRH, WT1, and MCSM on CRC were statistically significant. CONCLUSIONS: The gene methylation status of blood leukocytes may be associated with CRC risk. MCSM-H of blood leukocytes was associated with CRC, especially in younger people. Some dietary factors may affect hypermethylation status and influence susceptibility to CRC.
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Humans , Carcinogenesis , Case-Control Studies , China , Colorectal Neoplasms , DNA Methylation , Freezing , Fruit , Leukocytes , Methylation , Odds RatioABSTRACT
Objective To evaluate Persicae Semen-Rhei Radix et Rhizoma (PS-RRR) of different compatibility of acute blood stasis rats blood rheology and blood coagulation function, and to reveale the effect of PS-RRR for promoting blood circulation to remove blood stasis effect scope, nature, and degree of interaction. Methods With ice water bath and injected adrenaline hydrochloride copy of acute blood stasis rats model, different ratio (0:1, 1:5, 2:5, 2:3, 1:1, 3:2, 5:2, 5:1, and 1:0) of different concentration of PS-RRR was given for later. Through the determination of whole blood viscosity (WBV), blood sedimentation (ESR), erythrocyte aggregation index (EAI), prothrombin time (PT), partial thrombin (APTT), fibrinogen (FIB) content of coagulation, thrombin time (TT), and the blood rheology of blood stasis rats was observed, the influence of the blood coagulation indexes. Then response surface analysis and multi-index comprehensive index method of PS-RRR different compatibility of promoting blood circulation was used to remove blood stasis effect comprehensive comparative analysis. Results The ratio of PS-RRR between 2:3 to 3:2 showed obvious synergy (strength of synergy: -0.8); In PS dose from 5.5-10 g and RRR dose from 2.1-5.8 g area showed the antagonism function (antagonism effect strength maximum: 0.6); While other percentage did not show obvious synergy or antagonism. Conclusion The results of reveal that scope, nature, and degree of PS-RRR for promoting blood circulation to remove blood stasis interaction effect, the and its prescriptions of traditional Chinese medicine (TCM) and clinical use of PS-RRR 1:1 is consistent with the highest frequency of conclusion. PS-RRR provides scientific basis for clinical applications.
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Column chromatography was used for enrichment and separation of flavonoids, alkaloids and polysaccharides from the extracts of Morus alba leaves; glucose oxidase method was used with sucrose as the substrate to evaluate the multi-components of M. alba leaves in α-glucosidase inhibitory models; isobole method, Chou-Talalay combination index analysis and isobolographic analysis were used to evaluate the interaction effects and dose-effect characteristics of two components, providing scientific basis for revealing the hpyerglycemic mechanism of M. alba leaves. The components analysis showed that flavonoid content was 5.3%; organic phenolic acids content was 10.8%; DNJ content was 39.4%; and polysaccharide content was 18.9%. Activity evaluation results demonstrated that flavonoids, alkaloids and polysaccharides of M. alba leaves had significant inhibitory effects on α-glucosidase, and the inhibitory rate was increased with the increasing concentration. Alkaloids showed most significant inhibitory effects among these three components. Both compatibility of alkaloids and flavonoids, and the compatibility of alkaloids and polysaccharides demonstrated synergistic effects, but the compatibility of flavonoids and polysaccharides showed no obvious synergistic effects. The results have confirmed the interaction of multi-components from M. alba leaves to regulate blood sugar, and provided scientific basis for revealing hpyerglycemic effectiveness and mechanism of the multi-components from M. alba leaves.
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This study assessed the relationship between maternal nutritional knowledge in childcare practices and growth of children living in impoverished rural communities. This was an analytical cross-sectional study which covered a random sample of 991 children aged 0-36 month(s). Multivariate analysis showed that, after adjusting for potential confounders, there was a significant positive association between the childcare knowledge index and mean HAZ (β=0.10, p=0.005) but was not associated with mean WHZ. The strength of association increased among women of high socioeconomic status (β=0.15, p=0.014) but there was no significant association among women of low socioeconomic status. Increase in maternal childcare knowledge may contribute significantly to child’s nutritional status in Ghana if there is concurrent improvement in socioeconomic circumstances of women living in deprived rural communities.