Rolf Korsgaard

Carcinoma of the oral cavity in relation to aryl hydrocarbon hydroxylase inducibility, smoking and dental status

The authors investigated the smoking patterns in a consecutive series of 20 patients with oral cancer and at the same time assessed the aryl hydrocarbon hydroxylase (AHH) inducibility distribution and dental status. The AHH level proved high in 8 patients, intermediate in 7 and low in 5. High AHH inducibility was more common (p = less than 0.001) and low AHH inducibility less common (p = less than 0.001) than in the controls. Dental status was poor in only 2 patients. It is concluded that smoking is a prominent exogenous factor associated with the occurrence of cancer in the oral cavity. Poor dental status seems to be of minor importance.

Distribution and reproducibility of aryl hydrocarbon hydroxylase inducibility in a prospective population study of middle‐aged male smokers and nonsmokers

Aryl hydrocarbon hydroxylase (AHH) inducibility was determined in a lymphoblast test system in 2,000 consecutive middle‐ ged male smokers, 304 ex‐smokers, and 218 never‐smokers in the same birth‐year cohorts. Intraindividual, intraobserver, and interobserver, as well as temporal, reproducibility was checked in a special double‐blind quadruplet sample series from 20 other consecutive middle‐aged men. The results showed a three‐modal phenotype distribution of AHH inducibility with high (fold induction ⩾ 3.6), intermediate (2.6–3.6) and low (⩽2.5) levels ranging between 7.6% to 10.5%, 38.5% to 43.0%, and 46.5% to 53.9%, respectively, in all the smoking categories. The reproducibility of the measurements was excellent, with one‐way variance in the order of 0.007 to 0.033, and the applied assay method can therefore be used in large‐scale prospective population investigations. Such are required in order to establish a cause–effect association between high AHH inducibility and smoking‐related malignancies of the respiratory tract and oral cavity, as has been suggested from earlier retrospective studies in more limited clinical materials of cancers and precanceroses of these varieties. Cancer 56: 1988‐1994, 1985.

Mutagen sensitivity, smoking habits and enzyme induction in healthy middle-aged men

Unscheduled DNA synthesis (UDS) (excision-repair) of N-acetoxy-2-acetylaminofluorene (NA-AAF) damage to the DNA of human lymphocytes and levels of 3H-labeled NA-AAF bound to the DNA (carcinogen binding) of lymphocytes after 18 hr of culturing were measured in a consecutive subsample of healthy middle-aged males attending a multiphasic health screening program at the Department of Preventive Medicine in Malmö during 3 weeks in November-December 1981, and compared relative to their smoking habits, body weight, serum cholesterol, and gamma-glutamyltransferase levels as well as aryl hydrocarbon hydroxylase inducibility. This study group numbered 66 males and was uniform in sex, age, and investigation time. No case of significant arterial hypertension was present. The UDS and carcinogen binding results showed no correlation with the other factors measured, with the exception of smoking which was strongly (P less than 0.01) associated with increasing levels of both the UDS and carcinogen binding values. It is concluded that under ordinary circumstances smoking may represent the most important exogenous factor which may modulate risk to cardiovascular disease and cancer by influencing individual mutagen sensitivity.

Aryl hydrocarbon hydroxylase induction levels in patients with malignant tumors associated with smoking.

SummaryThe levels of aryl hydrocarbon hydroxylase (AHH) inducibility were assessed in 173 patients with cancers statistically associated with smoking, i.e., squamous cell and transitional cell carcinomas, at various sites. In 34 patients with carcinomas of the oral cavity, 41 patients with laryngeal carcinomas, and 22 patients with pulmonary carcinomas there was a highly significant overrepresentation of high inducers, whereas 30 patients with carcinomas of the renal pelvis and ureter and 46 patients with urinary bladder carcinomas did not differ significantly in this respect from a control population comprising 92 subject with no history of neoplastic disease.The results add further support to the concept of AHH as a major activator of carcinogens belonging to the group of polycyclic aromatic hydrocarbons (PAH) when these affect·the oral cavity and/or the respiratory tract.The role of AHH in urothelial carcinogenesis seems to be less explicit.

Leucoplakia of the oral cavity, smoking and arylhydrocarbon-hydroxylase inducibility

In a consecutive series of 53 cases of oral leucoplakia, smoking history, oro-dental status and arylhydrocarbon-hydroxylase (AHH) inducibility were assessed. There was an increased association of leucoplakia with smoking, particularly in the male cases, but no remarkable findings as to dental status. Overall, there was a slightly higher frequency of cases with high AHH inducibility than expected from a normal control population. This difference was confined to the smokers, where there was a statistically highly significant over-representation of high AHH inducibility and under-representation of low AHH inducibility. The figures in the non-smoking patients were close to the expected.

Oral and Oropharyngeal Cancer, Aryl Hydrocarbon Hydroxylase Inducibility and Smoking

In a series of 50 consecutive cases with oral or oropharyngeal malignancies, aryl hydrocarbon hydroxylase (AHH) inducibility and smoking habits were studied. 82% of the patients were smokers. The AHH levels were divided into high, intermediate and low groups and were correlated to a healthy control material also divided into the groups mentioned. A significant overrepresentation of patients with a high AHH level (p less than 0.0005) as well as an underrepresentation of low AHH levels (p less than 0.01) was found. Smokers with a high AHH level run a sixfold risk of developing cancer in this area and develop it earlier in life than people with low or intermediate AHH levels. Recurrences or secondary malignancies in the upper digestive tract or airways were substantially higher in the high AHH level group as compared to the other. A high AHH inducibility level thus is of both pathogenetic as well as prognostic importance in oral and/or oropharyngeal cancer.

Arylhydrocarbonhydroxylase Inducibility and Smoking Habits in Patients with Laryngeal Carcinomas

There is considerable evidence that the inducible enzyme aryl hydrocarbon hydroxylase (AHH) plays an important role in the activation of polycyclic aromatic hydrocarbons (PAH) to ultimate carcinogens. In man, a genetic heterogeneity of AHH inducibility has been demonstrated, and correlated to susceptibility to bronchogenic carcinomas following exposure to PAH. We assessed AHH inducibility in a control group of 102 healthy Swedish citizens and in 41 patients with laryngeal carcinomas. Frequencies of the three phenotypes of high, intermediate and low AHH inducibility in our control group; 8.8%, 42.2% and 49%, respectively, did not differ significantly from frequencies found in a white US population. In the laryngeal carcinoma group, there was a statistically highly significant overrepresentation of patients with high AHH inducibility, 36.6%, whereas 43.9% had an intermediate and 19.5% a low level. Most of the patients were heavy smokers. These findings add further support to the concept that susceptibility to PAH-induced carcinomas is associated with high levels of inducible AHH activity.

Laryngeal Cancer, Aryl Hydrocarbon Hydroxylase Inducibility and Smoking

In 58 cases with laryngeal cancer (10 supraglottic and 48 glottic), aryl hydrocarbon hydroxylase (AHH) inducibility and smoking habits were studied. All but 2 were smokers and most of them heavy tobacco consumers. The AHH levels were divided into high, intermediate and low groups and were compared to a large healthy control material also divided into the aforementioned groups. A highly significant overrepresentation of patients with a high AHH level (p less than 0.0005) as well as a significant underrepresentation of low AHH levels (p less than 0.025) were found. Smokers with a high AHH level run a fourfold risk of developing laryngeal cancer as compared to non-smokers with low AHH levels. They also develop cancer earlier in life and get recurrences and secondary malignancies more frequently. As in oral and oropharyngeal cancer a high AHH inducibility seems to be of pathogenetic as well as of prognostic importance even in laryngeal cancer.

Investigations of Smoking and Related Health Complications and Genotoxic Hazards in a Preventive Medical Population Program in Malmö, Sweden

Malmo is a Swedish city of 230,000 inhabitants, served by one general hospital. Since 1975, there has been an institute of Preventive Medicine integrated within the regular hospital servies at the Medical Department of Malmo General Hospital. The design of the department, as outlined in Fig. 1, seeks to avoid a conveyor-belt type of isolated “health check-ups,” and instead create an ambulatory ward for individual risk factor assessment and intervention. The investigative units can be used in the afternoon as outpatient clinics for further investigation and treatment of the risk factors identified in the screening, e.g., hyperlipidemia and hypertension as outlined in Fig. 2.