DNA methylation status is inversely correlated with green tea intake and physical activity in gastric cancer patients

Department of Molecular Oncology, Tokyo Medical and Dental University, Tokyo, Japan.
International Journal of Cancer (Impact Factor: 5.09). 06/2009; 124(11):2677-82. DOI: 10.1002/ijc.24231
Source: PubMed


Epigenetic silencing of genes by aberrant DNA methylation is recognized as a crucial component of the mechanism underlying tumorigenesis. However, the relationship between DNA methylation and the past lifestyle in cancer patients remains largely unknown. We examined the methylation statuses of 6 tumor-related genes, CDX2 (homeobox transcription factor), BMP-2 (bone morphogenetic protein 2), p16 (INK4A), CACNA2D3 (calcium channel-related), GATA-5 (transcription factor) and ER (estrogen receptor), in 106 primary gastric carcinomas by methylation-specific PCR and compared them with the past lifestyles of the patients. The methylation frequencies of the genes were 23.6, 21.7, 9.4, 32.4, 40.8 and 59.1%, respectively. Significant association was found between a decreased intake of green tea and methylation of CDX2 and BMP-2. More physical activity was correlated with a lower methylation frequency of CACNA2D3. Of these 6 genes, the methylation statuses of CDX2, BMP-2 and p16 revealed a significant interrelationship and those of CACNA2D3, GATA-5 and ER did likewise. Thus, some epidemiological factors, such as green tea intake, could be important as to determination of the methylation statuses of selected genes and may influence the development of cancer, including that of the stomach.

13 Reads
  • Source
    • "Regardless of the health status of the studied population , observational studies consistently show a weak correlation between physical activity and global or gene-specific DNA methylation. However, in most of these studies, physical activity was assessed via questionnaires at the time the study was conducted (Slattery et al. 2007, Pirola et al. 2012, Luttropp et al. 2013), before cancer onset (Yuasa et al. 2009), for the past week (Lott et al. 2012), for the past year (Coyle et al. 2007, Morabia et al. 2012, Zhang et al. 2012, White et al. 2013), the past 5 years (Coyle et al. 2007), the past 10 or 20 years (Slattery et al. 2007) and over a lifetime (Coyle et al. 2007). Therefore, the possibility of recall errors from the participants may have generated an important bias (Matthews 2002, Lissner et al. 2004). "
    [Show abstract] [Hide abstract]
    ABSTRACT: The response to exercise training (trainability) has been shown to have a strong heritable component. There is growing evidence suggesting that traits such as trainability do not only depend on the genetic code, but also on epigenetic signals. Epigenetic signals play an important role in the modulation of gene expression, through mechanisms such as DNA methylation and histone modifications. There is emerging evidence to show that physical activity influences DNA methylation in humans. The present review aims to summarize current knowledge on the link between DNA methylation and physical activity in humans. We have critically reviewed the literature and only papers focused on physical activity and its influence on DNA methylation status were included; a total of 25 papers were selected. We concluded that both acute and chronic exercise significantly impact DNA methylation, in a highly tissue- and gene-specific manner. This review also provides insights into the molecular mechanisms of exercise-induced DNA methylation changes, and recommendations for future research.This article is protected by copyright. All rights reserved.
    Acta Physiologica 10/2014; 213(1). DOI:10.1111/apha.12414 · 4.38 Impact Factor
  • Source
    • "Assessment of a large group of unrelated gastric cancer and normal tissue found that the CACNA2D3 CpG island was methylated in 30% of primary tumours, and 5.3% of normal tissue (Wanajo et al, 2008). A similar rate of methylation was reported in an independent cohort of gastric cancers (Yuasa et al, 2009). A significantly reduced survival time was found in tumours with methylation as compared with those with unmethylated CACNA2D3. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Calcium is an important intracellular messenger that mediates many biological processes that are relevant to the malignant process. Calcium ion channels are key in controlling the intracellular calcium, and little is known about their role in human cancer. We used qPCR and pyrosequencing to investigate expression and epigenetic regulation of the calcium channel regulatory subunit α(2)δ-3 (CACNA2D3) in breast cancer cell lines, primary cancers and metastatic lesions. Expression of CACNA2D3 mRNA is regulated in breast cancer cell lines by methylation in the CpG island located in the 5' regulatory region of the gene. Expression is upregulated by azacytidine (AZA) in cells with CpG island methylation but unaffected in cells lacking methylation. In primary breast carcinomas, methylation is more common in cancers, which subsequently relapse with loco-regional and, particularly, visceral metastatic disease in both oestrogen receptor-α (ER)-positive and -negative cases. Furthermore, CACNA2D3 CpG island is frequently methylated in breast cancer that has metastasised to the central nervous system. Methylation-dependent transcriptional silencing of CACNA2D3 may contribute to the metastatic phenotype of breast cancer. Analysis of methylation in the CACNA2D3 CpG island may have potential as a biomarker for risk of development of metastatic disease.
    British Journal of Cancer 05/2012; 107(2):375-81. DOI:10.1038/bjc.2012.231 · 4.84 Impact Factor
  • Source
    • "5.1. Clinical data As summarized in Table 3 and 24 studies to date have investigated the effects of structured exercise training on changes in circulating concentrations of host-related factors in persons with cancer (Allgayer et al., 2004, 2008a; Evans et al., 2009; Fairey et al., 2003, 2005a,b; Galvao et al., 2010; George et al., 2010; Irwin et al., 2006, 2007, 2005, 2009; Janelsins et al., 2011; Jones et al., 2012b; Ligibel et al., 2008; Na et al., 2000; Payne et al., 2008; Pierce et al., 2009; Schmitz et al., 2005; Segal et al., 2003, 2009; Tosti et al., 2011; Yuasa et al., 2009; Zeng et al., 2011). "
    [Show abstract] [Hide abstract]
    ABSTRACT: Over the past decade there has been increasing research and clinical interest in the role of exercise therapy/rehabilitation as an adjunct therapy to improve symptom control and management following a cancer diagnosis. More recently, the field of 'exercise - oncology' has broadened in scope to investigate whether the benefits extend beyond symptom control to modulate cancer-specific outcomes (i.e., cancer progression and metastasis). Here we review the extant epidemiological evidence examining the association between exercise behavior, functional capacity/exercise capacity, and cancer-specific recurrence and mortality as well as all-cause mortality individuals following a cancer diagnosis. We also evaluate evidence from clinical studies investigating the effects of structured exercise on blood-based biomarkers associated with cancer progression/metastasis as well findings from preclinical investigations examining the effects and molecular mechanisms of exercise in mouse models of cancer. Current gaps in knowledge are also discussed.
    Brain Behavior and Immunity 05/2012; 30. DOI:10.1016/j.bbi.2012.05.001 · 5.89 Impact Factor
Show more