Analysis of aromatic DNA adducts in laryngeal biopsies

Banaszewski, Jacek; Szmeja, Z; Szyfter, Witold; Szyfter, Krzysztof; Baranczewski, Paweł; Möller, Lennart

doi:10.1007/s004050050212

Cited by 10 publications

(5 citation statements)

References 20 publications

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“…Consistent with what we have previously reported (7,8), adduct levels were higher in nontumor cells compared with tumor cells. Several studies of other tissues that measured PAH-DNA adducts in both tumor and adjacent nontumor cells, including lung (38), laryngeal (39), pancreas (40), and liver (41), have also reported higher Research.…”

Section: Discussionmentioning

confidence: 98%

Polycyclic Aromatic Hydrocarbon–DNA Adducts in Prostate and Biochemical Recurrence after Prostatectomy

Rybicki

Neslund‐Dudas²,

Bock

et al. 2008

Clinical Cancer Research

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Purpose: DNA adduct levels may be influenced by metabolic activity, DNA repair capabilities, and genomic integrity, all of which play a role in cancer progression. Experimental Design: To determine if elevated DNA adducts are a marker for prostate cancer progression, we measured polycyclic aromatic hydrocarbon^DNA adducts by immunohistochemistry in prostate cells of 368 surgical prostate cancer patients treated at the Henry Ford Hospital in Detroit, Michigan, between September 1999 and July 2004. Patients were followed up to 5 years after surgery with relative risk for biochemical recurrence (BCR) estimated with a Cox proportional hazards model that adjusted for standard clinical risk factors. Results: At 1 year of follow-up, patients with adduct levels above the median in tumor cells [hazard ratio (HR), 2.40; 95% confidence interval (95% CI), 1.10-5.27] and nontumor cells (HR, 3.22; 95% CI, 1.40-7.39) had significant increased risk of BCR, but these HRs decreased to 1.12 (95% CI, 0.68-1.83) and 1.46 (95% CI, 0.89-2.41) in tumor and nontumor cells at 5 years postsurgery. When we restricted our analysis to patients with advanced-stage (III+) disease, those with high adduct levels in either tumor (53.5% versus 30.2%; P = 0.07) or nontumor (55.2% versus 28.6%; P = 0.02) cells had BCR rates almost 2-fold higher. In race-stratified analyses, the greatest risk of BCR associated with high adduct levels (in nontumor cells) was for African American patients younger than 60 years old (HR, 3.79; 95% CI, 1.01-14.30). Conclusions: High polycyclic aromatic hydrocarbon^DNA adduct levels in nontumor prostate cells are most strongly associated with BCR between 1 and 2 years after surgery and in patient subsets defined by younger age, advanced tumor stage, and African American race.

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Section: Discussionmentioning

confidence: 98%

Polycyclic Aromatic Hydrocarbon–DNA Adducts in Prostate and Biochemical Recurrence after Prostatectomy

Rybicki

Neslund‐Dudas²,

Bock

et al. 2008

Clinical Cancer Research

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“…It is significant, therefore, that it is still somewhat unclear which measures of tobacco smoke exposure are most highly correlated with smoking related DNA adduct levels. Several studies now support the idea that current smokers have higher adduct levels compared with former smokers, and that daily cigarette consumption (cigarettes per day) is the most predictive measure of variations in adduct levels in target (Wiencke et al, 1999;Szyfter et al, 1999a;Banaszewski et al, 2000;Romano et al, 1999) and surrogate tissues of current smokers Hou et al, 2001). In one study the daily cigarette tar consumed, but not the number of cigarettes, was found to be predictive of adduct levels in blood MNCs (Godschalk et al, 1998).…”

Section: Dna-adducts and Exposure To Lung Carcinogensmentioning

confidence: 98%

“…A series of studies have shown that smoking is associated with smoking related adducts in the oral cavity and larynx (Banaszewski et al, 2000;Szyfter et al, 1999a,b;Nath et al, 1998). In a casecontrol study, induced DNA adduct levels were found to be associated with risk of head and neck cancer (Li et al, 2001a).…”

Section: Dna Adducts Associated With Lung Cancermentioning

confidence: 99%

DNA adduct burden and tobacco carcinogenesis

Wiencke

2002

Oncogene

149

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DNA adducts associated with tobacco smoking could provide a marker of biologically effective dose of tobacco carcinogens and improve individual cancer risk prediction. A significant number of clinical and epidemiologic studies have reported associations of increased DNA adduct levels with the occurrence of the prevalent tobacco related cancers including cancer of the lung, head and neck, and bladder. The inducibility of DNA adducts following in vitro treatments using blood lymphocytes also appears to be a risk factor in the development of lung and head and neck cancer. Corroborative evidence pointing to the importance of DNA adducts in tobacco carcinogenesis include numerous studies showing associations of tobacco smoke exposure with the induction of DNA adducts in humans in vivo. Further effort is necessary, however, to more fully characterize the dose -response relationship between smoking and DNA adducts in exposed target and surrogate tissues. The relationship between gene polymorphisms thought to modify tobacco-related cancer risk and DNA adduct levels is complex. Results of some DNA adduct studies (both in vitro and in vivo) appear inconsistent with the epidemiologic findings. This is evident for polymorphisms involving both carcinogen metabolism (e.g. GSTP1) and DNA repair (e.g. XRCC1). Molecular studies of human tumors suggest associations of p53 mutation with DNA adducts and have revealed correlations of DNA adduct levels with somatic alterations (e.g. 3p21 LOH) that are thought to occur at the very earliest stages of tobacco carcinogenesis. More research is needed to assess the relationship between endogenous sources of DNA adducts and tobacco smoke exposure and the relative oncogenic effects of chemically stable versus unstable DNA adducts. Many potentially fruitful new avenues of cancer research are emerging that integrate DNA adduct analyses with assessments of smoking, genetics, diet and ambient air quality. These investigations aim to understand the multifactorial nature of interindividual variability in response to tobacco carcinogens. As these trends continue a variety of innovative study designs and approaches will become important in human populations.

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“…Aromatic DNA adducts could be localised in laryngeal biopsies of patients suffering from primary laryngeal carcinomas, with remarkable individual differences. Nevertheless, adduct levels were found to correlate with age, cigarette smoking and TNM gradings of tumours (Banaszewski et al 2000). The causal connection of laryngeal DNA adducts with PAH from tobacco smoke was considered very likely (Degawa et al 1994;Badawi et al 1996).…”

Section: Discussionmentioning

confidence: 97%

Cytochrome P450 1B1, a new keystone in gene-environment interactions related to human head and neck cancer?

Thier

Brüning²,

Roos

et al. 2002

Archives of Toxicology

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Alcohol consumption and tobacco smoking are major causes of head and neck cancers, and regional differences point to the importance of research into gene-environment interactions. Much interest has been focused on polymorphisms of CYP1A1 and of GSTM1 and GSTT1, but a number of studies have not demonstrated significant effects. This has mostly been ascribed to small sample sizes. In general, the impact of polymorphisms of metabolic enzymes appears inconsistent, with some reports of weak-to-moderate associations, and with others of no elevation of risks. The classical cytochrome P450 isoenzyme considered for metabolic activation of polycyclic aromatic hydrocarbons (PAH) is CYP1A1. A new member of the CYP1 family, CYP1B1, was cloned in 1994, currently representing the only member of the CYP1B subfamily. A number of single nucleotide polymorphisms of the CYP1B1 gene have been reported. The amino acid substitutions Val432Leu ( CYP1B1*3) and Asn453Ser ( CYP1B1*4), located in the heme binding domain of CYP1B1, appear as likely candidates to be linked with biological effects. CYP1B1 activates a wide range of PAH, aromatic and heterocyclic amines. Very recently, the CYP1B1 codon 432 polymorphism ( CYP1B1*3) has been identified as a susceptibility factor in smoking-related head-and-neck squamous cell cancer. The impact of this polymorphic variant of CYP1B1 on cancer risk was also reflected by an association with the frequency of somatic mutations of the p53 gene. Combined genotype analysis of CYP1B1 and the glutathione transferases GSTM1 or GSTT1 has pointed to interactive effects. This provides new molecular evidence that tobacco smoke-specific compounds relevant to head and neck carcinogenesis are metabolically activated through CYP1B1 and is consistent with a major pathogenetic relevance of PAH as ingredients of tobacco smoke.

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Analysis of aromatic DNA adducts in laryngeal biopsies

Cited by 10 publications

References 20 publications

Polycyclic Aromatic Hydrocarbon–DNA Adducts in Prostate and Biochemical Recurrence after Prostatectomy

Polycyclic Aromatic Hydrocarbon–DNA Adducts in Prostate and Biochemical Recurrence after Prostatectomy

DNA adduct burden and tobacco carcinogenesis

Cytochrome P450 1B1, a new keystone in gene-environment interactions related to human head and neck cancer?

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