Chronic cigarette smoking is associated with diminished folate status, altered folate form distribution, and increased genetic damage in the buccal mucosa of healthy adults

Gabriel, Helen E.; Crott, Jimmy W.; Ghandour, Haifa; Dallal, Gerard E.; Choi, Sang‐Woon; Keyes, Mary K.; Jang, Hyeran; Liu, Zhenhua; Nadeau, Marie; Johnston, Abbey; Mager, Donna L.; Mason, Joel B.

doi:10.1093/ajcn/83.4.835

Cited by 140 publications

(91 citation statements)

References 48 publications

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“…In the controls, the highest levels of in vitro BPDE-induced DNA adducts in current smokers followed by former smokers and never smokers we observed are consistent with the previous observation that smokers are significantly more sensitive to genotoxic challenges and thus have more DNA or chromosome damage than never smokers (17). Although smoking itself may have caused the formation of adducts in lymphocytic DNA, the in vivo smokinginduced DNA adduct levels were usually 100 to 1,000 times lower than the in vitro induced adduct levels observed in our previous (5) and current studies.…”

Section: Discussionsupporting

confidence: 92%

In vitro Benzo[a]pyrene Diol Epoxide–Induced DNA Adducts and Risk of Squamous Cell Carcinoma of Head and Neck

Wang

Chang

et al. 2007

Cancer Research

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In this large confirmatory study of 803 patients with squamous cell carcinoma of head and neck (SCCHN) and 839 controls frequency matched by age, sex, and ethnicity, we further examined potential predictors of benzo[a]pyrene diol epoxide (BPDE)-induced adduct levels and their associations with SCCHN risk. BPDE-DNA adduct levels were determined by the 32 P-postlabeling method in peripheral lymphocytes after in vitro challenged by BPDE. We also genotyped for GSTM1 null, GSTT1 null, GSTP1 Ile 105 Val, and GSTP1 Ala 114 Val. Potential predictors of BPDE-DNA adducts were evaluated by stratification and multivariate linear regression analyses and the association between adduct levels and SCCHN risk by multivariate logistic regression analyses. We found that mean BPDE-DNA adduct levels (the relative adduct labeling Â 10 7 F SD) were significantly higher in cases (77.6 F 111.8) than in controls (57.3 F 98.3; P < 0.001). Using the median control value (29.22) as a cutoff, 63% of the cases were distributed above this level (adjusted odds ratio, 1.71; 95% confidence interval, 1.39-2.10). A significant dose-response relationship was observed between adduct quartiles and SCCHN risk (P trend < 0.001). Multivariate linear regression analysis revealed that ethnicity and smoking were significant predictors of BPDE-DNA adduct levels in controls. In conclusion, we confirmed the previously reported association between in vitro BPDE-induced DNA adduct levels and SCCHN risk, and the assay may help identify individuals at high risk of developing smoking-related cancers. [Cancer Res 2007;67(12):5628-34]

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Section: Discussionsupporting

confidence: 92%

In vitro Benzo[a]pyrene Diol Epoxide–Induced DNA Adducts and Risk of Squamous Cell Carcinoma of Head and Neck

Wang

Chang

et al. 2007

Cancer Research

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“…It has been reported that smoking is associated with reduced levels of vitamins including B12, which is required for synthesis of S-adenyl-methionine. 20 This might be one factor causing the association of hypomethylation and smoking, but will require further study. Subset analysis within the tumor group also showed an association of alcohol use with hypomethylation, although it is difficult to separate tobacco and alcohol effects as they tend to be confounding characteristics in this patient population.…”

Section: Discussionmentioning

confidence: 99%

DNA global hypomethylation in squamous cell head and neck cancer associated with smoking, alcohol consumption and stage

Smith

Mydlarz

Mithani

et al. 2007

Intl Journal of Cancer

160

130

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Epigenetic changes have been implicated in the pathogenesis of solid tumors, including head and neck squamous cell carcinoma (HNSCC). Prior efforts have primarily examined regional promoter hypermethylation as a silencer of tumor suppressor gene expression. To analyze the global state of methylation in the HNSCC genome, we utilize pyrosequencing of repetitive elements (LINEs) to compare the state of global methylation in HNSCC to normal aerodigestive mucosa. 137 samples (119 HNSCC tumors and 18 normal mucosal tissues) were digested to extract DNA and subjected to bisulfite treatment. Treated DNA was amplified using PCR primers for the repetitive LINEs sequence and produced a heterogeneous sample of products, from many genomic loci. These products were pyrosequenced to quantitatively evaluate their global genomic methylation status. HNSCC specimens showed global hypomethylation, with a mean level of genomic methylation of 46.8% methylated with a standard deviation of 9.0. Conversely, the normal upper airway mucosa had a global methylation level of 54.0 and a standard deviation of 4.6 (Mann-Whitney p value < 0.001). The tumor specimens also showed an increasing degree of hypomethylation associated with advanced tumor stage (ANOVA p-value of 0.003). About 67% of HNSCC's are globally hypomethylated when evaluated against the minimum level of methylation in the normal mucosal specimens. Degree of global hypomethylation was associated with smoking history, alcohol use and stage in univariate analysis (p-value 0.02), however, only HNSCC diagnosis remained significant on multivariate analysis. Despite the presence of regional promoter hypermethylation, HNSCC demonstrates global genomic hypomethylation. The effects of stage, alcohol use and smoking on global hypomethylation were not independently significant. ' 2007 Wiley-Liss, Inc.Key words: DNA hypomethylation; head and neck squamous cell carcinoma; pyrosequencing; epigenetics; smoking exposure; tobacco Head and neck squamous cell carcinomas (HNSCCs) account for 3% of all cancers in the United States and 40,000 new cases each year.1 Although significant progress has been made in the areas of early detection, diagnosis and treatment, the 5-year survival rate for patients with HNSCC has shown only modest improvement in the past 40 years.2 Comprehensive analysis of clinical and treatment factors has shown tumor-site specific improvements in 5-year survival for cancers of the nasopharynx, oropharynx and hypopharynx, and late-stage laryngeal cancer. The molecular mechanisms of HNSCC carcinogenesis are undergoing intensive investigation. Despite significant genetic/ epigenetic alterations found in these cancers, few known alterations correlate with the clinical outcomes of the disease. Epigenetic changes have been characterized in the pathogenesis of HNSCC. By far, the most studied epigenetic mechanism has been promoter hypermethylation of tumor suppressor genes including: Cyclin A1, MGMT, DCC and p16. 4 Methylation of cytosineguanine dinucleotides by the enzyme class of DN...

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“…A separate publication, which describes the relationships between micronuclei and onecarbon nutrients, contains some of the data on BMC micronuclei and the dietary intake of macronutrients (36).…”

Section: Methodsmentioning

confidence: 99%

A Comparison of Carotenoids, Retinoids, and Tocopherols in the Serum and Buccal Mucosa of Chronic Cigarette Smokers versus Nonsmokers

Gabriel

Liu

Crott

et al. 2006

Cancer Epidemiology, Biomarkers &Amp; Prevention

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Background: Cigarette smoking, a major risk factor for oropharyngeal cancer, is reported to alter oral levels of carotenoids and tocopherols. Such effects may be important because these nutrients, as well as retinoids, are putative chemoprotective agents. Objectives: To determine whether chronic smoking is associated with altered concentrations of these nutrients in serum and buccal mucosa; to distinguish whether such effects are ascribable to diet; and to determine whether oral concentrations of these nutrients correlate with a putative biomarker of oral cancer risk. Methods: Serum and buccal mucosal cells (BMC) were analyzed for these nutrients and for BMC micronuclei in smokers (n = 35) and nonsmokers (n = 21). Results: General linear regression with adjustments for dietary intake showed that smokers possess lower serum concentrations of B-and A-carotene, cryptoxanthin, lutein,

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Chronic cigarette smoking is associated with diminished folate status, altered folate form distribution, and increased genetic damage in the buccal mucosa of healthy adults

Abstract: Chronic smoking is associated with a lower systemic status of several B vitamins, reduced oral folate, and changes in folate form distribution in the mouth. However, the cytologic damage that is evident in the mouths of smokers does not correlate with oral folate status.

Cited by 140 publications

References 48 publications

In vitro Benzo[a]pyrene Diol Epoxide–Induced DNA Adducts and Risk of Squamous Cell Carcinoma of Head and Neck

In vitro Benzo[a]pyrene Diol Epoxide–Induced DNA Adducts and Risk of Squamous Cell Carcinoma of Head and Neck

DNA global hypomethylation in squamous cell head and neck cancer associated with smoking, alcohol consumption and stage

A Comparison of Carotenoids, Retinoids, and Tocopherols in the Serum and Buccal Mucosa of Chronic Cigarette Smokers versus Nonsmokers

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