Wolf-Dieter Heller

Tobacco and alcohol and the risk of head and neck cancer

SummaryWe carried out two case-control studies on the relative risk of head and neck cancer in association with tobacco and alcohol consumption. The first study carried out at the ENT Department of the University hospitals of Heidelberg and Giessen (FRG) comprised 200 male patients with squamous cell cancer of the head and neck and 800 control subjects matched for sex, age, and residential area (1:4 matching design). Of the tumour patients, 4.5% had never smoked, in contrast to 29.5% of the control group. The average tobacco and alcohol consumption of the patients was approximately twice as high as in the control subjects. The highest alcohol and tobacco consumption was observed in patients suffering from oropharyngeal cancer. Tobacco and alcohol increased the risk of head and neck cancer in a dose-dependent fashion and acted as independent risk factors. In heavy smokers (> 60 pack-years) a relative risk of 23.4 (alcohol adjusted) was calculated. Combined alcohol and tobacco consumption showed a synergistic effect. The risk ratio increased more in a multiplicative than in an additive manner. Oral and laryngeal cancer were associated with the highest tobacco-associated risk values. The highest ethanol-associated risk values were associated with oropharyngeal and laryngeal cancer. The second study was carried out at the ENT Department of the University of Heidelberg on 164 males with squamous cell carcinoma of the larynx and 656 control subjects matched for sex, age and residential area (1:4 matching design). Of the cases, 4.2% had never smoked, compared with 28.5% of the control subjects. The risk of laryngeal cancer by tobacco consumption was dose dependent, reaching a maximum value of 9.1 (adjusted for alcohol) for a consumption of more than 50 tobacco-years (TY). The relative risk of laryngeal cancer associated with alcohol intake was also dose dependent, reaching a value of 9.0 (adjusted for tobacco) for a mean daily consumption of more than 75 g alcohol. An analysis of subsite specific risks showed that heavy smokers (> 50 TY) carried a nearly ten times higher risk of supraglottic cancer than of glottic cancer. The risk of supraglottic cancer from alcohol consumption was also higher than that of glottic cancer.

Double-blind study on the effect of cigarette smoking on the chromosomes of human peripheral blood lymphocytes in vivo

A double-blind study with 170 smokers and 124 non-smokers revealed a doubling of the frequencies of exchange-type aberrations in the peripheral blood lymphocytes of smokers as compared with non-smokers. Smokers (N = 24) had 1 SCE more per metaphase than non-smokers (N = 20), an effect that is significant but low when compared with the effect on structural chromosomal aberrations. These results show that structural chromosomal aberrations are better indicators of the genetical effects of low chronic exposures to mutagens in man than SCEs. The frequencies of micronuclei in 3-day lymphocyte cultures showed no differences in smokers (N = 95) and non-smokers (N = 39). Non-smokers (N = 99) had significantly higher frequencies of 2nd metaphases in 48-h cultures in vitro than smokers (N = 141), indicating an effect of smoking on the stimulation of lymphocytes by PHA in vitro.

Dental Status and Oral Hygiene in Patients with Head and Neck Cancer

Poor oral hygiene is believed to play a role as a risk factor for head and neck cancer, especially for oral cancer. Only few epidemiologic data exist about dental status and oral hygiene in these patients. We performed a case-control study involving 100 patients with squamous cell carcinoma of the upper aerodigestlve tract and 214 age- and sex-matched control subjects with no known tumorous disease. In the tumor patients, oral hygiene and dental status proved to be significantly worse: The majority of the tumor patients seldom or never brushed their teeth and the frequency of dental visits was significantly lower. Tartar of 3 mm or more was found in 40.9% of the tumor patients and in 22% of the control subjects. In the tumor group, the incidence of decayed teeth was significantly higher compared with the control subjects. Chronic Inflammation of the gingiva was observed in 28% of the tumor patients vs. 13.5% in the control gorup. Oral hygiene was negatively correlated with alcohol as well as with tobacco consumption. The social status of subjects also correlated with oral hygiene, which was found to be worst in subjects from the lower social strata. The present study revealed a poor dental status and oral hygiene in patients with head and neck cancer. The pathogenetic mechanism being associated with this suspected risk factor remains to be investigated.

Determination of nicotine and cotinine in human serum and urine: an interlaboratory study.

An interlaboratory study aimed at determining nicotine and cotinine in human serum and urine was carried out. 11 laboratories from 6 countries, all experienced in performing nicotine and cotinine determinations in biological fluids by radioimmunoassay (RIA) and/or gas chromatography (GC) were involved. Each of them received 18 serum and 18 urine samples. The specimens were obtained from 8 smokers and 10 non-smokers; 2 samples from non-smokers were spiked with defined amounts of nicotine and cotinine. All the laboratories distinguished perfectly between the smokers and the non-smokers and according to cotinine levels in serum the laboratories ranked the samples with good agreement. There were systematic differences in the absolute values between the laboratories. The ratios of urinary cotinine concentrations between active and passive smokers differed widely from laboratory to laboratory. The reasons for this are not yet known and necessitate further investigation.

Mutagenic Activity of Cigarette Smoke

Smoking is made responsible for a variety of cancers in man and it is estimated that some 30% of all cancer deaths in the USA are caused by smoking (Doll and Peto 1981; The Health Consequences of Smoking 1982; Smoking and Health 1979). The finding that cigarette smoke is mutagenic in a variety of test systems including somatic cells of man may be helpful to a better understanding of the mechanisms by which smoking leads to cancer. These data also support the mutation theory of the origin of cancer which was already formulated by Boveri in 1914 and elaborated by Bauer in 1928 (see also Bauer 1963).

Misclassification of Smoking in a Follow-up Population Study in Southern Germany

Smoking prevalence in southern Germany was studied in 1984-1985 using a representative cohort of 4022 subjects aged 25 to 64 years, with 3753 reinterviewed in 1987-1988. Data were available for analysis from interviews on self-reported smoking behavior and from serum cotinine measurements in both investigations. More men than women reported current smoking, and particularly heavy smoking. Serum cotinine levels increased steadily with the daily number and nicotine yield of cigarettes smoked. Mean cotinine levels in ex-smokers were higher than those in never smokers, suggesting that a higher percentage of current smokers are misclassified as ex-smokers than never smokers. Using cotinine rather than self-reported smoking data increased the proportion of true smokers in the subgroup of self-reported smokers by about 3% in males and by about 1% in females. Data from the reinterviews revealed that reported smoking status confirmed by cotinine measurement in 1987-1988 conflicted in a number of cases with the data obtained in 1984-1985 using the same procedure. For example, 0.1% of those who stated they were current regular smokers, 4.3% of those who stated they were current occasional smokers, and 17.6% of those who stated they were ex-smokers in 1984-1985 claimed in 1987-1988 to have never smoked. This misclassification of ex-smokers was higher in women. Altogether the true proportion of ex-smokers among self-reported never smokers was about 9.7% (17.8% in men and 6.7% in women). The widely variable uptake of tobacco smoke by smokers, as well as the misclassification of true smokers and ex-smokers as never smokers, needs to be considered in epidemiological studies evaluating the health risks from both active and passive smoking.

Risk Factors of Cancer of the Larynx: Results of the Heidelberg Case—Control Study

Squamous cell carcinoma of the larynx is a multifactorial disease. It is firmly linked to several environmental risk factors. In the meanwhile, a considerable amount of epidemiologic evidence has been built up to implicate chronic consumption of alcohol and tobacco, occupation, diet, and social status in the etiology of the laryngeal cancer. Herein is a report from the first case-control study on the role of these risk factors conducted in a German population of patients with laryngeal cancer.

Haemoglobin adducts from aromatic amines and tobacco specific nitrosamines in pregnant smoking and non smoking women

In non-smokers, haemoglobin adducts from 3- and 4-aminobiphenyl have been reported to arise mainly from exposure to environmental tobacco smoke (ETS). Therefore, the impact of self-reported smoking (n = 27) and exposure of non-smokers to ETS (n = 78) on haemoglobin adducts was studied in pregnant women from Homburg, Germany. In addition to 3- and 4-aminobiphenyl, adducts from seven monocyclic aromatic amines (aniline, o -, m -, and p -toluidine, 2,4-dimethylaniline, 2-ethylaniline and o -anisidine) and the adduct from tobacco-specific nitrosamines (4-hydroxy-1-(3-pyridyl)1-butanone) were determined. Five of 78 self-reported non-smoking women had plasma cotinine levels and urinary cotinine/creatinine ratios indicative of active smoking. In the remaining 73 non-smokers cotinine/creatinine ratios correlated significantly with self reported exposure to ETS. However, none of the haemoglobin adducts increased with increasing exposure to ETS or increasing cotinine/creatinine ratios. Although significantly elevat...In non-smokers, haemoglobin adducts from 3- and 4-aminobiphenyl have been reported to arise mainly from exposure to environmental tobacco smoke (ETS). Therefore, the impact of self-reported smoking (n = 27) and exposure of non-smokers to ETS (n = 78) on haemoglobin adducts was studied in pregnant women from Homburg, Germany. In addition to 3- and 4-aminobiphenyl, adducts from seven monocyclic aromatic amines (aniline, o -, m -, and p -toluidine, 2,4-dimethylaniline, 2-ethylaniline and o -anisidine) and the adduct from tobacco-specific nitrosamines (4-hydroxy-1-(3-pyridyl)1-butanone) were determined. Five of 78 self-reported non-smoking women had plasma cotinine levels and urinary cotinine/creatinine ratios indicative of active smoking. In the remaining 73 non-smokers cotinine/creatinine ratios correlated significantly with self reported exposure to ETS. However, none of the haemoglobin adducts increased with increasing exposure to ETS or increasing cotinine/creatinine ratios. Although significantly elevated in smoking compared with non-smoking women, the mean haemoglobin adduct levels formed by tobacco-specific nitrosamines (54 7 8 9 vs 26 7 4 1 fmol g-1, p < 0 001), 3-aminobiphenyl (3 0 0 5 vs 1 4 0 1 pg g-1, p < 0 001), 4-aminobiphenyl (27 9 3 4 vs 10 2 0 7 pg g-1, p < 0 001), o -toluidine (289 25 vs 237 65 pg g-1, p < 0 001), p -toluidine (315 32 vs 197 13 pg g-1; p < 0 001), 2,4-dimethylaniline (25 5 2 9 vs 18 6 1 6 pg g-1, p < 0 05), had considerable overlappings ranges indicating lack of specificity as biomarkers to tobacco smoke exposure. Exposure to other as yet unknown environmental sources appearsto be more significant than previously thought.

Determinants of children's exposure to environmental tobacco smoke (ETS): A study in Southern Germany

Maternal smoking has been repeatedly found to be the most important determinant of childrens exposure to environmental tobacco smoke (ETS). Here, we further investigated predictors for the urinary cotinine/creatinine ratio (CCR, ng/mg) in 1220 preschool children for the year 1996. Children from smoking homes (35.1%) had significantly higher CCR than children from nonsmoking homes (mean: 55.5 vs. 14.9 ng/mg). The level of education of the parents was a strong predictor for CCRs even after adjusting for number of cigarettes smoked, maternal smoking and dwelling space. Additionally, dwelling space was inversely related to childrens urinary cotinine level. The CCR- levels in children investigated in 1996 and 1998 were significantly correlated (Pearsons r=0.67). The parents of 806 children agreed for a visit to their homes. In 79 of the 536 (14.7%) of the self-reported, nonsmoking households, smoking was admitted during the visit. The mean urinary CCR of these children was 25.2 ng/mg. We conclude that in addition to parental smoking behaviour, other variables such as dwelling space and social and educational status predict the childrens exposure to ETS. Our data also revealed that a considerable percentage of parents denied the ETS exposure of their children at home.

Hydroxyproline excretion in urine of smokers and passive smokers

Urinary hydroxyproline excretion was investigated in 125 male cigarette smokers, 194 male pipe and/or cigar smokers, and 24 male nonsmokers. Hydroxyproline excretion was calculated either as hydroxyproline/creatinine ratio or as body surface-standardized amounts of hydroxyproline excreted in urine sampled during day, during night, or over 24 hr. The association of hydroxyproline excretion with smoke uptake variables such as daily cigarette consumption, carboxyhemoglobin, serum cotinine, and nicotine in urine and with self-reported passive smoking exposure in nonsmokers was analyzed. The hydroxyproline/creatinine ratio was found to be unsuitable as a measure of hydroxyproline excretion since creatinine urine concentrations correlate inversely with smoke uptake in cigarette and pipe/cigar smokers. The amount of hydroxyproline excreted in 24-hr urine and standardized for body surface was not significantly associated with smoke uptake in pipe/cigar smokers or exposure to passive smoking in nonsmokers. In cigarette smokers the situation appeared similar, although the results were less clear-cut. The data do not favor the premise that measuring urinary hydroxyproline excretion is an accurate method of investigating a lung-damaging effect of smoking, passive smoking, or air pollution.