MTHFR C677T genetic polymorphism in combination with serum vitamin B2, B12 and aberrant DNA methylation of P16 and P53 genes in esophageal squamous cell carcinoma and esophageal precancerous lesions: a case–control study

Pan, Da; Su, Ming; Huang, Guiling; Luo, Pengfei; Zhang, Ting; Fu, Lingmeng; Wei, Jie; Wang, Shaokang; Sun, Guiju

doi:10.1186/s12935-019-1012-x

Cited by 16 publications

(28 citation statements)

References 55 publications

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“…The study was approved by the Institutional Review Board of Southeast University Zhongda Hospital (no. 2012ZDllKY19.0) [46][47][48] , in accordance with the Declaration of Helsinki. All subjects signed written informed consent in the study, and the informed consent was obtained from legal guardian for the illiterate population.…”

Section: Methodsmentioning

confidence: 99%

Roles of drinking and diet in the U-shaped relationship between smoking and BMI in middle-aged and elderly Chinese rural adults

Pan

Wang

et al. 2020

Sci Rep

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The study aimed to investigate the relationship between smoking and BMI, from the perspective of the roles of alcohol drinking and dietary factors in a rural population. We analysed cross-sectional data from 10,837 middle-aged and elderly Chinese rural adults who completed a questionnaire that included questions on demographic characteristics, dietary intake, and detailed smoking and drinking status. Results showed that current smokers had lower BMI and consumed foods less frequently (except coriander, onion, garlic, hawthorn and fermented bean curd) than non-smokers. The relationship between smoking amount and the risk of overweight or obesity was U-shaped, and the trends were also similar by stratum of baseline age groups (all p for interaction < 0.001). Heavy smokers tended to have drinking habits, which was associated with increased BMI (all p for trend < 0.001). Additionally, despite the lower risk of overweight or obesity for current smokers, normal weight individuals were found to have the minimum smoking amount. In conclusion, smoking may cause suppression of appetite but smokers tend to have other unhealthy habits relating to increased BMI. Dietary factors and alcohol use play important roles in the U-shaped relationship between smoking behaviours and BMI in the middle-aged and elderly Chinese rural population.

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Section: Methodsmentioning

confidence: 99%

Roles of drinking and diet in the U-shaped relationship between smoking and BMI in middle-aged and elderly Chinese rural adults

Pan

Wang

et al. 2020

Sci Rep

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“…This suggests that nutrition and genetics/epigenetics may have an even greater role to play in carcinogenesis than the single effect seen to date. Furthermore, 5,10-methylenetetrahydrofolate reductase (MTHFR) is the central enzyme in folate metabolism and is responsible for the circulation form of folate, as well as its activity in the DNA methylation process [9]. It has been reported that MTHFR C677T polymorphism and folate status can interact in ways which impact DNA methylation status as well, which in turn affects cancer risk [29,55].…”

Section: Discussionmentioning

confidence: 99%

“…Previous studies reported a distinct epidemiological pattern of EPL in Huai'an District and the consumption of alcohol and tobacco products, which has been the key risk factors in many regions. However, these factors only played a minor role in the EPL risk, with other factors such as genetic polymorphism, environmental exposures, and dietary factors reported to take the main responsibility for esophageal carcinogenesis in this endemic region [7][8][9][10]36].…”

Section: Study Subjects and Epl Diagnosismentioning

confidence: 93%

“…The best results of reducing the proportion of cancer patients who are diagnosed at late stages are associated with an early diagnosis, which is commonly known as the "early stages" [3]. Therefore, esophageal squamous dysplasia, which is the recognized esophageal precancerous lesion (EPL) for ESCC, has been of greater interest over the last decade [4][5][6][7][8][9][10]. A previous study indicated that 24% of mild dysplasia, 50% of moderate dysplasia, and 74% of severe dysplasia could develop ESCC during a 3.5-year period [6].…”

Section: Introductionmentioning

confidence: 99%

“…In the last decade, gene-nutrition interactions have been studied. For example, our recent study indicated that the serum levels of vitamin B 2 and B 12 and genetic polymorphism may interact in ways which has a different effect on the risks of EPL and ESCC [9]. Previous molecular epidemiological studies also investigated the gene-nutrition interactions between dietary folate intake and aberrant DNA methylation in ESCC based on a food frequency questionnaire (FFQ) [29,30], but the exact serum level of folate was never assessed in these interactions.…”

Section: Introductionmentioning

confidence: 99%

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Moderately high folate level may offset the effects of aberrant DNA methylation of P16 and P53 genes in esophageal squamous cell carcinoma and precancerous lesions

Wang

Pan

et al. 2020

Genes Nutr

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Background This study evaluated gene-nutrition interactions between folate and the aberrant DNA methylation of tumor suppressor genes in different stages of carcinogenesis of esophageal squamous cell carcinoma (ESCC). Methods Two hundred ESCC cases, 200 esophageal precancerous lesion (EPL) cases, and 200 controls matched by age (± 2 years) and gender were used for this study. Baseline data and dietary intake information was collected via questionnaire. The serum folate levels and methylation status of promoter regions of p16 and p53 were detected. Results The interactions of increased serum folate level with unmethylated p16 and p53 promoter regions were significantly associated with a reduced risk of both EPL and ESCC (p for interaction < 0.05). The interactions of the lowest quartile of serum folate level with p16 or p53 methylation was significantly associated with an increased risk of ESCC (OR = 2.96, 95% CI, 1.45–6.05; OR = 2.34, 95% CI, 1.15–4.75). An increased serum folate level was also related to a decreasing trend of EPL and ESCC risks when p16 or p53 methylation occurred. The interaction of spinach, Chinese cabbage, liver and bean intake with unmethylated p16 and p53 was significantly associated with a reduced risk of EPL or ESCC (p for interaction < 0.05). Conclusions The interactions between a high folate level and unmethylated p16 and p53 promoter regions may have a strong preventive effect on esophageal carcinogenesis. Additionally, a high folate level may offset the tumor-promoting effects of aberrant DNA methylation of the genes, but it is also noteworthy that a very high level of folate may not have a protective effect on EPL in some cases.

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Feasibility of using P16 methylation as a cytologic marker for esophageal squamous cell carcinoma screening: A pilot study

et al. 2022

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Background Early diagnosis and treatment of esophageal squamous cell dysplasia (ESCdys) and esophageal squamous cell carcinoma (ESCC) could significantly reduce the incidence and mortality of ESCC. This pilot study aimed to investigate whether P16/CDKN2A methylation could serve as a cytologic biomarker for early detection of ESCdys and ESCC. Methods Paired esophageal biopsy and cytology specimens (exfoliated cells) were obtained from subjects at different stages of ESCC development. The methylation status of P16 gene in these two specimen types was determined using a 115‐bp MethyLight assay. Categorical data were compared by the Chi‐square test. Logistic regression was performed to assess adjusted odds ratios of P16 methylation associated with ESCC and ESCdys. Prediction models for identifying individuals at risk of ESCC and high‐grade ESCdys (high‐grade intraepithelial neoplasia, HGIN) were developed by multivariable logistic regression. Diagnostic performance was evaluated using receiver operating characteristic (ROC) analysis. Internal validation of the prediction models was performed using the 1000‐bootstrap resample. Results A total of 105 subjects with diagnoses ranging from normal mucosa through ESCC were included in this study. An increase in P16 methylation frequency was observed with increasing severity of esophageal lesions (p for trend <0.001). In the adjusted logistic regression models, P16 methylation in cytology specimens was positively associated with ESCC and ESCdys risk, whereas P16 methylation in biopsy specimens was only associated with a higher risk of developing ESCC. The predictive capacity of base model I (AUC, 0.816) for ESCC and HGIN was significantly increased by adding P16 methylation in cytology specimens (model III; AUC, 0.882; p = 0.043), but not P16 methylation in biopsy specimens (model II; AUC, 0.850; p = 0.225). Bootstrap validation showed optimism‐corrected AUC of 0.789 for model I, 0.822 for model II, and 0.854 for model III. Conclusion P16 methylation as a cytologic marker was associated with the ESCC development and has the potential for application in minimally invasive ESCC screening.

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MTHFR C677T genetic polymorphism in combination with serum vitamin B2, B12 and aberrant DNA methylation of P16 and P53 genes in esophageal squamous cell carcinoma and esophageal precancerous lesions: a case–control study

Cited by 16 publications

References 55 publications

Roles of drinking and diet in the U-shaped relationship between smoking and BMI in middle-aged and elderly Chinese rural adults

Roles of drinking and diet in the U-shaped relationship between smoking and BMI in middle-aged and elderly Chinese rural adults

Moderately high folate level may offset the effects of aberrant DNA methylation of P16 and P53 genes in esophageal squamous cell carcinoma and precancerous lesions

Feasibility of using P16 methylation as a cytologic marker for esophageal squamous cell carcinoma screening: A pilot study

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