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Results for “global DNA methylation”

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At least 19 recordsLinked to original sources

PubMed2000

Immunohistochemical evaluation of global DNA methylation: comparison with in vitro radiolabeled methyl incorporation assay.

The in vitro radiolabeled methyl incorporation assay, a commonly used technique to evaluate global methylation of DNA, has some disadvantages and limitations. The purpose of the present study was to compare the results of global DNA methylation evaluated by radiolabeled methyl incorporation (CPM/microg of DNA) with immunohistochemical staining of the same tissue sections with a monoclonal antibody developed against 5-methylcytosine used (5-mc). We archival specimens of squamous cell cancer (SCC) of the human lung with a matched uninvolved specimen (n = 18 pairs) and 18 lung specimens from subjects without lung cancer (noncancer specimens) to make this comparison. The immunostaining for 5-mc was reported as a percentage of cells positive for staining as well as a weighted average of the intensity score. The results suggested that both radiolabeled methyl incorporation assay and immunostaining for 5-mc can be used to demonstrate hypomethylation of DNA in SCC tissues compared to matched uninvolved tissues. An advantage of immunostaining, however, is its ability to demonstrate hypomethylation of SCC compared to adjacent bronchial mucosa on the same archival specimen, obviating the need to use sections from both SCC and matched uninvolved tissues. Only by using the immunostaining technique were we able to document a statistically significant difference in DNA methylation between SCC and noncancer tissues. We conclude that the immunostaining technique has advantages over the radiolabeled methyl incorporation assay and may be best suited for evaluation of global DNA methylation when the methylation status of cancer cannot be normalized by methyl incorporation of normal tissues or when the number of samples available for evaluation is small.

5-Methylcytosine↗

PubMed2007

Global DNA methylation level in whole blood as a biomarker in head and neck squamous cell carcinoma.

BACKGROUND: Head and neck squamous cell carcinoma (HNSCC) is commonly associated with tobacco and alcohol exposures, although dietary factors, particularly folate, and human papillomavirus, are also risk factors. Epigenetic alterations are increasingly implicated in the initiation and progression of cancer. Genome-wide (global) hypomethylation seems to occur in early neoplasia and is a feature of genomic DNA derived from solid tumor tissues, including HNSCC. This study aimed to determine whether global methylation in DNA derived from whole blood, a proxy tissue, is associated with HNSCC and to assess potential modification of this property by environmental or behavioral risk factors. METHODS: Global DNA methylation levels were assessed using a modified version of the combined bisulfite restriction analysis of the LRE1 sequence in a population-based case-control study of HNSCC from the Boston area. RESULTS: Hypomethylation lead to a significant 1.6-fold increased risk for disease (95% confidence interval, 1.1-2.4), in models controlled for other HNSCC risk factors. Smoking showed a significant differential effect (P < 0.03) on blood relative methylation between cases and controls. Furthermore, in cases, variant genotype in the MTHFR gene and low folate intake showed relationships with decreased global methylation, whereas in controls, antibody response to human papillomavirus 16 was associated with an increased global methylation level. DISCUSSION: DNA hypomethylation in nontarget tissue was independently associated with HNSCC and had a complex relationship with the known risk factors associated with the genesis of HNSCC.

Alcohol Drinking↗

PubMed1995

Cytological evaluation of global DNA methylation in mouse testicular genome.

Global methylation of DNA from different testicular cell types has been studied by DNA end-labeling and nick translation of fixed chromatin (in situ), following digestion with cytosine methylation-sensitive restriction enzymes. Both at the level of chromatic (chromosome) and naked DNA, there is extensive methylation of the genome. Although the extent of methylation was nearly the same among different cell types in the MspI, HpaII, and HhaI digested end-labelled DNA, in the chromosome preparations the digestion patterns varied in cell type-specific manner, pachytene being the most sensitive and spermatids and sperm the most resistant. The differential sensitivity is attributable to the difference in the chromatin organisation in different testicular cell types though no specific region could be identified as particularly more sensitive or resistant to the enzymes. Pachytene bivalents do not reveal a consistent segmental pattern of digestion, but the perichiasmate regions of diplotene/diakinesis and metaphase I chromosomes show hypersensitivity to the enzymes.

Animals↗

PubMedDate not supplied

Effect of cell cycle growth arrest on global DNA methylation status in human lung epithelial-like (A549) cells.

BACKGROUND: Decreased global DNA methylation have been previously shown in A549 cells exposed to prolonged hyperoxia. Because hyperoxia induces growth arrest in these cells, whether the status of global DNA methylation changed in response to cellular growth arrest was of interest. MATERIALS AND METHODS: A549 cells were growth arrested at either the S- or G2/M-phase of the cell cycle by exposure to resveratrol (25 microM), or colcemid (0.1 microg/ml) for 24 h. In addition, to determine the kinetics of hyperoxia-induced growth arrest, cells were exposed to either 1 day of normoxia or 1-5 days of hyperoxia. RESULTS: The data indicate hyperoxia-induced G2/M growth arrest after day 2 of exposure onwards. Moreover, 66.5% of cells were synchronized at the S-phase after exposure to resveratrol and 97% of them at the G2/M-phase after exposure to colcemid. No changes in global DNA methylation status were observed in cells synchronized at either phase of the cell cycle. CONCLUSION: These findings indicate that global DNA methylation in A549 cells is not determined primarily by hyperoxia-induced cell cycle growth arrest.

Antineoplastic Agents, Phytogenic↗

PubMed2026

Prognostic Role of Global DNA Methylation in Renal Cancer Reveals Decitabine Treatment Benefit.

BACKGROUND: Renal cancer presents a significant global health challenge due to its rising incidence and mortality rates. Often undetected in early stages, it complicates diagnosis and treatment. Current therapies face resistance and limited effectiveness, especially in advanced stages. The diverse subtypes of renal cancer highlight the need for new biomarkers and risk assessment tools for targeted treatments. OBJECTIVE: This study aims to assess the prognostic significance of global DNA methylation (GM) levels in renal cancer, identify new biomarkers, and evaluate the therapeutic potential of the DNA methyltransferase inhibitor decitabine. METHODS: Data on RNA sequencing, gene mutations, DNA methylation, and clinical outcomes were collected from TCGA and GEO databases. We calculated global DNA methylation scores (GMS) and categorized patients into high, intermediate, and low GMS groups. Survival analysis and genomic analyses were conducted to explore the relationships between GMS, clinical outcomes, and tumor characteristics. RESULTS: Higher GMS was identified as an independent prognostic factor associated with worse outcomes in renal cancer. Patients with elevated GMS showed increased mutations, copy number variations, and a more aggressive tumor phenotype. Treatment with decitabine was observed to reduce tumor hypermethylation and downregulate cell cycle pathway activity, indicating potential therapeutic benefits. CONCLUSION: Global DNA methylation plays a significant role in renal cancer prognosis. GMS may serve as valuable biomarkers for prognosis and personalized treatment strategies. Decitabine shows potential efficacy for high GMS patients, particularly through its impact on cell cycle regulation, underscoring the importance of personalized approaches in cancer treatment.

Humans↗

PubMed2005

Global DNA methylation evaluation: potential complementary marker in differential diagnosis of thyroid neoplasia.

The implications of global DNA hypomethylation were recently reported in several models of tumorigenesis. Little is known about this epigenetic event in thyroid neoplasia. The study aimed to evaluate the status of global DNA methylation in several types of thyroid tumors using a monoclonal antibody specific for 5-methylcytidine (5-mc) and to define the diagnosis potential of this marker. 5-mc immunostaining scores were calculated in 17 papillary thyroid carcinomas (PTC), 6 follicular thyroid carcinomas (FTC), 16 follicular adenomas (FA), 19 nodular goiters (NG) and ten Hürthle cells adenomas (HCA). The expression of galectin-3 was also evaluated. Computerized image analysis showed a significant lower level of 5-mc immunostaining in thyroid carcinoma when compared with benign tumors or adjacent normal thyroid parenchyma (P<0.0001). Overall, 5-mc accuracy to distinguish malign from benign thyroid tumors was similar to that of galectin-3 (89% versus 87%, P>0.05). The combination of 5-mc with galectin-3 led to an excellent accuracy level of 96%. Among follicular neoplasia 5-mc accuracy to differentiate malign tumors trends to be higher than galectin-3 one (90% versus 66%, P=0.06). These data stress the necessity of epigenetic events evaluation among thyroid nodules and propose global DNA methylation assessment as a potential diagnostic tool to combine with other valuable markers.

Adenocarcinoma↗

PubMed2005

Pattern of nonspecific (or global) DNA methylation in oral carcinogenesis.

BACKGROUND: Although alterations in nonspecific (or global) DNA methylation (GDM) in specific cells are known to be involved in the process of lung carcinogenesis, similar associations have not been evaluated in other smoking-related cancers of the head and neck. METHODS: We evaluated the status of GDM by using monoclonal antibodies specific for 5-methylcytosine (5-mc) in oral squamous cell carcinoma (SCC) specimens of 48 cigarette smokers who had SCC develop and in 93 age-, race-, and sex-matched smokers who did not. RESULTS: Percentages of cells positive for 5-mc immunostaining of DNA of SCC and dysplastic lesions were significantly higher than those of normal oral epithelial cells from cancer subjects and from noncancer subjects. The degree of DNA methylation was unrelated to DNA content. CONCLUSIONS: The pattern of GDM in oral SCCs is different from that of lung SCCs. The differences in nutrient risk factor profiles that are related to GDM and differential activity of DNA methyltranferases between oral and lung SCCs may explain these observations.

5-Methylcytosine↗

PubMed2004

A simple method for estimating global DNA methylation using bisulfite PCR of repetitive DNA elements.

We report a method for studying global DNA methylation based on using bisulfite treatment of DNA and simultaneous PCR of multiple DNA repetitive elements, such as Alu elements and long interspersed nucleotide elements (LINE). The PCR product, which represents a pool of approximately 15 000 genomic loci, could be used for direct sequencing, selective restriction digestion or pyrosequencing, in order to quantitate DNA methylation. By restriction digestion or pyrosequencing, the assay was reproducible with a standard deviation of only 2% between assays. Using this method we found that almost two-thirds of the CpG methylation sites in Alu elements are mutated, but of the remaining methylation target sites, 87% were methylated. Due to the heavy methylation of repetitive elements, this assay was especially useful in detecting decreases in DNA methylation, and this assay was validated by examining cell lines treated with the methylation inhibitor 5-aza-2'deoxycytidine (DAC), where we found a 1-16% decrease in Alu element and 18-60% LINE methylation within 3 days of treatment. This method can be used as a surrogate marker of genome-wide methylation changes. In addition, it is less labor intensive and requires less DNA than previous methods of assessing global DNA methylation.

Alu Elements↗

PubMed2001

Altered global methylation of DNA: an epigenetic difference in susceptibility for lung cancer is associated with its progression.

Alterations in global DNA methylation have been observed in many cancers, but whether such alterations represent an epigenetic difference in susceptibility for the disease is unknown. The status of global DNA methylation also has not been reported in intact or specific types of cells involved in the carcinogenic process. To address these issues in lung carcinogenesis, we evaluated the status of global DNA methylation by using a monoclonal antibody specific for 5-methylcytosine (5-mc) in randomly selected lung specimens of 60 cigarette smokers who developed squamous cell carcinoma (SCC) and 30 cigarette smokers who did not. 5-mc immunostaining scores of DNA of SCC (0.61 +/- 0.42) and associated hyperplastic lesions (0.82 +/- 0.27) was significantly lower than those of DNA of histologically normal bronchial epithelial cells (0.99 +/- 0.52) and hyperplastic lesions (1.2 +/- 0.22) of noncancer specimens. The ratio of 5-mc scores between SCC and matched uninvolved bronchial epithelial cells was significantly associated with advanced stage and size of the tumor. The results suggest that alteration in global DNA methylation is an important epigenetic difference in susceptibility for the development of lung cancer. The reduced global DNA methylation in SCC compared with epithelial hyperplasia and its association with tumor size and disease stage is suggestive of its involvement in the progression of SCC. The results also indicate that normal methylation of DNA in epithelial hyperplastic lesions may prevent the transformation of these lesions to invasive cancer. If these results are confirmed, the status of DNA methylation in early lesions such as epithelial hyperplasia could be used to identify smokers who are at risk for the development of SCC.

5-Methylcytosine↗

PubMed2005

Stable loss of global DNA methylation in the radiation-target tissue--a possible mechanism contributing to radiation carcinogenesis?

Radiation-induced lymphomagenesis and leukemogenesis are complex processes involving both genetic and epigenetic changes. Although genetic alterations during radiation-induced lymphoma- and leukemogenesis are fairly well studied, the role of epigenetic changes has been largely overlooked. Rodent models are valuable tools for identifying molecular mechanisms of lymphoma and leukemogenesis. A widely used mouse model of radiation-induced thymic lymphoma is characterized by a lengthy "pre-lymphoma" period. Delineating molecular changes occurring during the pre-lymphoma period is crucial for understanding the mechanisms of radiation-induced leukemia/lymphoma development. In the present study, we investigated the role of radiation-induced DNA methylation changes in the radiation carcinogenesis target organ--thymus, and non-target organ--muscle. This study is the first report on the radiation-induced epigenetic changes in radiation-target murine thymus during the pre-lymphoma period. We have demonstrated that acute and fractionated whole-body irradiation significantly altered DNA methylation pattern in murine thymus leading to a massive loss of global DNA methylation. We have also observed that irradiation led to increased levels of DNA strand breaks 6 h following the initial exposure. The majority of radiation-induced DNA strand breaks were repaired 1 month after exposure. DNA methylation changes, though, were persistent and significant radiation-induced DNA hypomethylation was observed in thymus 1 month after exposure. In sharp contrast to thymus, no significant persistent changes were noted in the non-target muscle tissue. The presence of stable DNA hypomethylation in the radiation-target tissue, even though DNA damage resulting from initial genotoxic radiation insult was repaired, suggests of the importance of epigenetic mechanisms in the development of radiation-related pathologies. The possible role of radiation-induced DNA hypomethylation in radiation-induced genome instability and aberrant gene expression in molecular etiology of thymic lymphomas is discussed.

Animals↗

PubMed2000

Folate deficiency diminishes the occurrence of aberrant crypt foci in the rat colon but does not alter global DNA methylation status.

BACKGROUND AND AIMS: It has been suggested that a diminished folate status may enhance colorectal carcinogenesis by causing DNA hypomethylation. The aims of the present study were to assess the impact of different levels of folate depletion on azoxymethane (AOM)-induced aberrant crypt foci (ACF) formation and DNA hypomethylation in the colon of male Sprague-Dawley rats. METHODS: Rats, aged 4 weeks, were divided into four groups and were fed semipurified diets either containing adequate folate (control), devoid of folate (FD) or FD + 1% succinylsulfathiazole before AOM treatment (FD1) or during the last 4 weeks of the study (FD2). At 8 weeks of age, all animals received subcutaneous injections of AOM once weekly for 3 weeks at a dose rate of 15 mg/kg bodyweight. Animals were necropsied 6 weeks after the last AOM injection and the ACF were visualized under light microscopy in formalin-fixed, methylene blue-stained colons. RESULTS: Blood folate concentrations were significantly depleted (P < 0.001) in the treatment groups consuming folate deplete diets, with the FD2 treatment group having significantly lower folate levels compared with all other groups. Higher plasma homocysteine concentrations (P < 0.001) were observed in the groups that exhibited diminished blood folate levels. There were no significant differences in global DNA methylation in the liver or colonic mucosa between the four groups, despite some groups exhibiting marked folate depletion. Animals with the most severe folate deficiency (FD2) had a lower final bodyweight and had significantly fewer ACF in their colon (P < 0.05) compared with control animals. Total (mean +/- SEM) ACF counts were as follows: control 286+/-24; FD 290+/-25; FD1 218+/-32; and FD2 205+/-27. CONCLUSIONS: In this model, folate deficiency diminished the occurrence of ACF but did not alter global DNA methylation status in the colon.

Animals↗

PubMed2003

Global DNA methylation in relation to hMLH1 and hMSH2 protein immunoreactivity in sporadic human endometrial carcinomas.

Overall DNA methylation status was studied in a group of 28 sporadic human endometrial carcinomas (ECs) using the [32P]-postlabeling technique. Moreover, expression of the DNA mismatch repair proteins (hMLH1 and hMSH2) was investigated in ECs using immunohistochemistry. Mean 5-methyldeoxycytosine (m5dC) content in the studied group was 3.48+/-0.37% (range, 2.89-4.12%). The mean m5dC scores were significantly different between early (3.35+/-0.33%) and advanced (3.66+/-0.36%) endometrial neoplasms (chi2-test; p=0.03). There was a markedly increased overall DNA methylation with the degree of histological differentiation and with the infiltration of the myometrium (p<0.05). Loss of hMLH1 and hMSH2 expression was reported in 7 (25%) and 5 (18%) tumors, respectively, but the immunoreactivity did not correlate with the known clinicopathological variables of cancer. In addition, no obvious correlation was found between global m5dC content and the lack of hMLH1 and hMSH2 protein expression in human uterine tumors (p=0.97 and p=0.19 for hMLH1 and hMSH2, respectively; Spearman's rank correlation test). Our results clearly show that alterations in global DNA methylation may influence tumor progression, but they are not directly associated with the inactivation of the mismatch-repair machinery in sporadic human ECs.

Adaptor Proteins, Signal Transducing↗

PubMed2005

Dietary arsenic affects dimethylhydrazine-induced aberrant crypt formation and hepatic global DNA methylation and DNA methyltransferase activity in rats.

Cell culture studies have suggested that arsenic exposure results in decreased S-adenosylmethionine (SAM), causing DNA hypomethylation. Previously, we have shown that hepatic SAM is decreased and/or S-adenosylhomocysteine increased in arsenic-deprived rats; these rats tended to have hypomethylated DNA. To determine the effect of dietary arsenic on dimethylhydrazine (DMH)-induced aberrant crypt formation in the colon, Fisher 344 weanling male rats were fed diets containing 0, 0.5, or 50 microg As (as NaAsO2)/g. After 12 wk, dietary arsenic affected the number of aberrant crypts (p<0.02) and aberrant crypt foci (p<0.007) in the colon and the amount of global DNA methylation (p<0.04) and activity of DNA methyltransferase (DNMT) (p<0.003) in the liver. In each case, there were more aberrant crypts and aberrant crypt foci, a relative DNA hypomethylation, and increased activity of DNMT in the rats fed 50 microg As/g compared to those fed 0.5 microg As/g. The same phenomenon, an increased number of aberrant crypts and aberrant crypt foci, DNA hypomethylation, and increased DNMT tended to hold when comparing rats fed the diet containing no supplemental arsenic compared to rats fed 0.5 microg As/g. The data suggest that there is a threshold for As toxicity and that possibly too little dietary As could also be detrimental.

Animals↗

PubMed1999

Hypomethylation of an expanded FMR1 allele is not associated with a global DNA methylation defect.

The vast majority of fragile-X full mutations are heavily methylated throughout the expanded CGG repeat and the surrounding CpG island. Hypermethylation initiates and/or stabilizes transcriptional inactivation of the FMR1 gene, which causes the fragile X-syndrome phenotype characterized, primarily, by mental retardation. The relation between repeat expansion and hypermethylation is not well understood nor is it absolute, as demonstrated by the identification of nonretarded males who carry hypomethylated full mutations. To better characterize the methylation pattern in a patient who carries a hypomethylated full mutation of approximately 60-700 repeats, we have evaluated methylation with the McrBC endonuclease, which allows analysis of numerous sites in the FMR1 CpG island, including those located within the CGG repeat. We report that the expanded-repeat region is completely free of methylation in this full-mutation male. Significantly, this lack of methylation appears to be specific to the expanded FMR1 CGG-repeat region, because various linked and unlinked repetitive-element loci are methylated normally. This finding demonstrates that the lack of methylation in the expanded CGG-repeat region is not associated with a global defect in methylation of highly repeated DNA sequences. We also report that de novo methylation of the expanded CGG-repeat region does not occur when it is moved via microcell-mediated chromosome transfer into a de novo methylation-competent mouse embryonal carcinoma cell line.

Adult↗

PubMed2003

Dietary folate and selenium affect dimethylhydrazine-induced aberrant crypt formation, global DNA methylation and one-carbon metabolism in rats.

Several observations suggest a role for DNA methylation in cancer pathogenesis. Although both selenium and folate deficiency have been shown to cause global DNA hypomethylation and increased cancer susceptibility, the nutrients have different effects on one-carbon metabolism. Thus, the purpose of this study was to investigate the interactive effects of dietary selenium and folate. Weanling, Fischer-344 rats (n = 23/diet) were fed diets containing 0 or 2.0 mg selenium (as selenite)/kg and 0 or 2.0 mg folate/kg in a 2 x 2 factorial design. After 3 and 4 wk of a 12-wk experiment, 19 rats/diet were injected intraperitoneally with dimethylhydrazine (DMH, 25 mg/kg) and 4 rats/diet were administered saline. Selenium deficiency decreased (P < 0.05) colonic DNA methylation and the activities of liver DNA methyltransferase and betaine homocysteine methyltransferase and increased plasma glutathione concentrations. Folate deficiency increased (P < 0.05) the number of aberrant crypts per aberrant crypt foci, the concentration of colonic S-adenosylhomocysteine and the activity of liver cystathionine synthase. Selenium and folate interacted (P < 0.0001) to influence one-carbon metabolism and cancer susceptibility such that the number of aberrant crypts and the concentrations of plasma homocysteine and liver S-adenosylhomocysteine were the highest and the concentrations of plasma folate and liver S-adenosylmethionine and the activity of liver methionine synthase were the lowest in rats fed folate-deficient diets and supplemental selenium. These results suggest that selenium deprivation ameliorates some of the effects of folate deficiency, probably by shunting the buildup of homocysteine (as a result of folate deficiency) to glutathione.

5-Methyltetrahydrofolate-Homocysteine S-Methyltran↗

PubMed2004

Correlation between the DNA global methylation status and progesterone receptor expression in normal endometrium, endometrioid adenocarcinoma and precursors.

Endometrial carcinomas are the most common malignancy of the female genital tract and the third most common cancer in women. Progesterone and oestrogen receptors (PRs, ERs) are the most widely documented prognostic and predictive factors in endometrioid adenocarcinoma. Besides the hormonal pathway involved in the progression of preneoplastic and neoplastic lesions, alterations of the DNA methylation status have been shown to be an early signal of tumorigenesis. In this study, we show that in normal endometrium, during the proliferative phase, DNA methylation and PR expression are high, with a significant decline towards the end of the secretory phase and a gradual increase in non-atypical and atypical endometrial hyperplasia; they reach their highest level in grade I, then decrease significantly in grade-II and grade-III endometrioid adenocarcinomas. During each stage, a significant positive correlation is observed between DNA methylation and PR (P<0.0001). The strong parallelism between DNA methylation and PR expression precludes establishing a precise determination regarding the timing of these events, clearly involved in the genesis of endometrioid adenocarcinoma.

Carcinoma, Endometrioid↗

PubMed2003

Quantitation by image analysis of global DNA methylation in human spermatozoa and its prognostic value in in vitro fertilization: a preliminary study.

OBJECTIVE: To determine the relationship between sperm DNA methylation level and sperm characteristics and pregnancy rates. DESIGN: Prospective study. Quantitation by image analysis of DNA methylation in sperm nucleus. SETTING: Department of Reproduction Biology, Edouard Herriot Hospital, Lyon, France. PATIENT(S): Infertile couples undergoing IVF-ET. INTERVENTION(S): The immunostaining of 5 methyl-cytosine was performed on the spare sperm suspension that was used for an assisted reproduction technology procedure. MAIN OUTCOME MEASURE(S): Sperm characteristics according to World Health Organization criteria, sperm motility parameters with computer-assisted semen analysis, sperm DNA methylation level, and heterogeneity index (HI). RESULT(S): Sperm DNA methylation level and HI are correlated with sperm DNA characteristics. HI is negatively correlated with fertilization rate; sperm DNA methylation level is correlated with pregnancy rate. CONCLUSION(S): The DNA methylation level in human spermatozoa could be a new approach to evaluating the ability of spermatozoa to fertilize and lead to normal embryo development.

3,3'-Diaminobenzidine↗

PubMed2003

Race- and age-dependent alterations in global methylation of DNA in squamous cell carcinoma of the lung (United States).

OBJECTIVE: The current study investigated the race- and age-dependent alterations in global DNA methylation on the development and progression of squamous cell carcinomas (SCCs) of the lung. METHODS: Methylation status was evaluated in SCC and in the associated uninvolved bronchial mucosa (UBM) and epithelial hyperplasia (EH) of 53 Whites and 23 African Americans by using an antibody specific for 5-methylcytosine (5-mc). A low 5-mc score indicates global hypomethylation of DNA. RESULTS: 5-mc scores of SCC were significantly lower compared to 5-mc scores of UBM and EH in Whites (p < 0.05). In African Americans, 5-mc scores of SCCs were not significantly different from 5-mc scores of UBM and EH, suggesting an involvement of methylation in the development of SCCs in Whites, but not in African Americans. 5-mc scores were lower in younger subjects compared to older subjects in Whites. Since cancers in younger subjects tend to be more aggressive than cancers in older subjects, these observations may suggest that hypomethylation may have contributed to aggressiveness cancers of younger Whites. Hypomethylation of SCCs in White men was associated with shorter survival from the disease. CONCLUSIONS: These preliminary results suggest that the methylation status of DNA may affect the development, aggressiveness, and prognosis of SCCs in Whites.

Age Factors↗