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

Abstract

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.

Trends in Incidence and Mortality of Esophageal Cancer in Huai’an District, a High-Risk Area in Northern Jiangsu Province, China

“… 36 , 37 Additionally, genetic factors such as genetic polymorphism, DNA methylation, and gene-nutrition interaction were also found to be significantly associated with the risk of EC. 2 , 5 , 18 …”

“…36,37 Additionally, genetic factors such as genetic polymorphism, DNA methylation, and gene-nutrition interaction were also found to be significantly associated with the risk of EC. 2,5,18 Similarly, with the city-town-village tertiary cancer prevention and treatment network established in Yangzhong County, 21 the local residents aged between 35-75 from 27 towns in Huai'an District were covered and eligible for a free routine endoscopy examination in EDETPEC, and the rate of compliance reached approximately 80% in total. Therefore, over the past several decades, with socio-economic development, lifestyle changes, the popularization of health education, and the intervention of EDETPEC, the living and nutritional conditions of the local residents have been greatly improved, and the esophageal precancerous lesions or EC can be detected at early stages.…”

“…15 , 16 However, although many EC studies have been conducted in Huai’an District, detailed EC statistics and the trend of incidence of the district have never been reported in previous studies. 3 , 6 , 17 - 19 Therefore, this study aimed to provide a detailed report of EC statistics and a clear comparable figure of the trends in incidence and mortality rates of EC in Huai’an District, Huai’an City, Jiangsu Province, China between 1998-2016. This was based on the cancer registry report provided by Huai’an District Center for Disease Control and Prevention (CDC).…”

The relationship between P16INK4A and TP53 promoter methylation and the risk and prognosis in patients with oesophageal cancer in Thailand

“…In this research, we exploited an approach to study complex environmental factors and epigenetics in EC. The aetiology and pathogenesis of EC involve complicated interactions between epigenetic, genetic and environmental factors, and it is a complex progressive disease with multiple stages 6 . The results indicated tobacco smoking and alcohol consumption as the major risk factors for EC and its probable role inducing promoter methylation in the upper gastrointestinal tract.…”

“…Numerous studies have revealed that the P16 gene is frequently found to be methylated in EC 28 – 30 . A previous study also suggested that aberrant DNA hypermethylation may be a consequence of various environmental, lifestyle-behaviour and dietary factors dependent on the specific region that result in an elevated susceptibility to EC 6 , 31 . Similarly, a recent study showed that EC related to smoking and drinking involves P16 silencing resulting from the promoter region hypermethylation 32 , 33 .…”