Ernest L. Wynder

Environmental factors of cancer of the colon and rectum II. Japanese epidemiological data

This is an epidemiological study of 107 patients with large bowel cancer and 307 control patients interviewed in Japan. Colon cancer is significantly less common in Japan, but rectal cancer is as common in Japan as it is in the United States. Japanese patients with cancer of the colon have a higher socioeconomic status than rectal cancer patients. Associated with the higher status is a more Western style diet. It is suggested that perhaps dietary fat influences the make‐up of the bacterial flora and thus affects the pathogenesis of cancer of the colon. No significant relationship was found to medical and surgical diseases nor to the cholesterol and weight levels.

An epidemiological investigation of cancer of the endometrium

One hundred‐twelve endometrial cancer patients and 200 comparison patients were interviewed in New York hospitals. Additionally, the hospital records of more than 900 patients with endometrial cancer were reviewed. The most important factor found related to cancer of the endometrium is obesity. Tallness, in addition to obesity, enhances the risk of endometrial cancer distinctly. Other differences between the cancer patients and the comparison subjects, including late menopause, heavy menstrual bleeding and premenstrual breast swelling, suggest that the etiological basis for endometrial cancer may be increased retention of certain endogenous hormones. The most practical preventive measure for endometrial cancer appears to be an effective reduction in weight although the epidemiological proof of the consequences remains to be given.

The role of alcohol and tobacco in multiple primary cancers of the upper digestive system, larynx and lung: a prospective study.

Abstract A five year prospective study was conducted on 733 patients admitted to Memorial Sloan-Kettering Cancer Center with a single primary epidermoid carcinoma of the oral cavity, pharynx or larynx, diagnosed between 1965 and 1968. The survival in women at five years following diagnosis of the index cancer was significantly better than in men. The average annual incidence for second primary carcinomas of the respiratory and upper digestive systems was 18.2 per 1000 in men and 15.4 per 1000 in women. The women were distinguished from the men by their less intensive exposure to tobacco and alcohol previous to the index cancer. The risk of developing a second primary cancer was enhanced significantly by more intensive, combined exposures to tobacco and alcohol prior to the index cancer. Within the first five years after the clinical presentation of the index cancer, the development of any new neoplastic process previously initiated in the exposed tissues was unaffected by altered smoking and drinking habits after the index cancer. Of the 433 deaths occurring at five years in the study population, two-thirds were attributed to metastases or the complications of treatment of a single or multiple primary cancer of the oral cavity, pharynx or larynx, 1.5% to a new primary cancer of the lung or esophagus and 1.4% to a new primary cancer of an organ outside of the respiratory and upper digestive tracts. The significant excesses in cancer mortality in men and women were particularly evident between 45–64 years of age and were distributed throughout all levels of exposure to tobacco and alcohol. The underlying cause in 30.7% was due to diseases other than cancer. Future follow-up will enable us to determine the risk of new primary cancers and intercurrent nonneoplastic diseases in patients who continue to smoke and/or drink, and whether these risks, as suggested by our retrospective study, are enhanced as a result of previous radiation therapy.

Epidemiology of cancer of the ovary

One hundred‐fifty ovarian cancer patients plus eight with a diagnosis other than adenocarcinoma and endometrioid cancers and 300 age‐matched control patients were interviewed in New York hospitals. There were no essential differences in marital status, nor in other marital or pregnancy factors. The study suggested a trend for more ovarian cancer patients to have dysmenorrhea. These data may be artifactitious and further studies in this area are indicated. Among the gynecologic findings, the ovarian cancer patient gave a more frequent history of heavy menstrual bleeding and earlier menopause than the control group. A comparison of mortality rates in Americans and Japanese Americans suggests possible differences in the etiologic background of pre‐ and postmenopausal ovarian cancer patients. The increase of ovarian cancer among Japanese immigrants to the U.S. represents a primary lead to the etiology of this type of cancer. It is suggested that further work done on Japanese, Japanese‐Americans, and other native Americans in terms of the effect of diet on steroids with particular reference to their effect on various target organs.

A study of tobacco carcinogenesis. XI. Tumor initiators, tumor accelerators, and tumor promoting activity of condensate fractions.

The neutral portion of cigarette smoke condensate, its fraction B, and subtraction BI are the only portions of cigarette smoke condensate which are active as carcinogens and tumor initiators. BI amounts to about 0.6% of dry “tar” and contains polynuclear aromatic hydrocarbons (PAH), N‐ and O‐heteroaromatic compounds, chlorinated insecticides, and some of their pyrolysis products, esters, terpenes, and quinones. Heretofore, 12 known carcinogens and several tumor accelerators have been identified. BI was separated into 5 portions. The active portion (BIh, 0.09%) was chromatographed into 80 subtractions. BIh 56‐66 were highly active as tumor initiators, but did not contain known carcinogens; BIh 71‐78 contained known as well as unidentified carcinogens. Such alkylated PAH, as alkylated fluoranthenes, cyclopentaphenanthrenes, and chrysenes, are present in significant concentration in the active BIh sub‐fractions. Of all tobacco “tar” fractions, only the acidic portion showed significant tumor promoting activity.

Smoking and cardiovascular disease: Effect of nicotine on the serum epinephrine and corticoids

Abstract After a 40 minute rest in a sitting posture, the catecholamines, corticoids, and FFA levels in the serum were determined prior to and after smoking cigarettes under standard conditions of inhalation. Increasing the nicotine content in the smoke progressively increased the epinephrine-but not the norepinephrine-content in the serum. Increasing the number of low-nicotine cigarettes smoked also led to an elevation of epinephrine. The serum corticoids were markedly elevated on smoking high-nicotine cigarettes. The FFA changes were not related to either the amount of nicotine inhalation or the elevation of serum E. The possible epidemiologic implications of these findings were briefly discussed.

A study of the epidemiology of cancer of the breast. II. The influence of hysterectomy.

A study was undertaken to investigate the relationship of artificial menopause to breast cancer and to determine the reliability of patient response to questions about the type and extent of pelvic surgery experienced. Hospital records of 1596 breast cancer patients between 1954-1959 were compared with 1573 controls. Interviews with an additional 280 breast cancer patients and 280 controls (matched for age and religion) during 1959-1960 were substantiated by hospital descriptions of the pelvic surgery. It was found that nearly half of the women did not know or failed to relate the correct extent of pelvic surgery which they had experienced. These data were analyzed to determine frequency of artificial menopause frequency of artificial menopause by marital status frequency of castration type of operation interval before the onset of breast cancer and age at operation. The relative risk of developing breast cancer among women with a history of artificial menopause was calculated as .71 in the record and .70 in the interview study. The risk was found to be .56 among castrated women and .86 among noncastrated women. Women who were castrated prior to age 37 had a risk of less than .17. It is concluded that these findings are in agreement with those which show that reduction of the estrogen level in women through castration or cessation of menstruation as through long-term lactation will reduce the incidence of breast cancer. The interesting aspects of breast cancer revealed by the present study should undergo further evaluation in a prospective study.

Epidemiologic investigation of multiple primary cancer of the upper alimentary and respiratory tracts. I. A retrospective study

In a retrospective investigation of 104 patients with multiple primary tumors of the upper alimentary and respiratory tracts, the data suggest that patients who smoke heavily before developing cancer are more likely to develop second, primary tumors. Continued smoking after initial diagnosis or radiation therapy for the first primary is associated with an increased frequency of second primary tumors. Discontinuance of smoking and drinking after the first primary provides no assurance against the development of a second primary cancer.

Aetiological Factors in Mouth Cancer

History has always been one of mans best teachers, a truism which applies also to mans quest to comprehend the nature of disease. We call to mind Snows classical study on cholera through the use of epidemiological techniques. Through his observations a disease was curtailed and the mechanistn of an illness more closely understood at a time when its exact pathogenesis was unestablished. To be learned from this historical study, too, is that one does not need to understand the mechanism of a disease completely in order to accomplish a reduction of its incidence. This point is stressed because it represents the basis of current epidemiological studies in the field of cancer. While many factors may induce cancer and the basic mechanism of cancer is still beyond our reach, we know factors which do play a part in the development of cancer whose removal or reduction will lead to a decrease in incidence of this disease. This is the primary goal of the epidemiologist in his fight against any disease. If a given factor is found to contribute to a disease it is of little importance to the patient whether this factor was of causative or of catalytic nature. What matters to the population is whether the removal of a given factor will reduce the incidence of a given disease. The present investigation on aetiological factors of cancer of the oral cavity was designed to serve towards this end. This report, to be presented in greater detail elsewhere, will outline some of the factors which influence the development of cancer of the mouth and whose control can lead to a drastic reduction in this type of cancer (Wynder, Bross, and Feldman, 1957).

EXPERIMENTAL TOBACCO CARCINOGENESIS.

Publisher Summary The primary purpose of laboratory investigations in the field of tobacco carcinogenesis is to determine if various tobacco and tobacco smoke products might prove to be carcinogenic to different animal species and tissues, and to determine the components responsible for this activity. Once such components are identified, their removal or reduction is investigated. Reviewing the biological and chemical studies involving tumorigenic and cilia-toxic activity of tobacco products, fractions and single components, the chapter presents a discussion of pertinent analytical techniques employed, of different biological procedures utilized, of precursors that give rise to certain components, and of some fundamental aspects. The characteristics of tobacco and tobacco smoke such as tobacco products, physical state of tobacco smoke, smoking machines and smoking techniques, preparation of tobacco smoke, tobacco extracts, and combustion and smoke temperatures have also been discussed in the chapter. Biological tests for tumorigenic activity are tobacco smoke condensate, tobacco extracts, tobacco smoke, tobacco smoke condensate fractions, and cilia-toxic components. Components of tobacco and tobacco smoke listed in this chapter are considered to possess tumorigenic and cilia-toxic activity. Reduction of tumorigenic activity can be achieved by reduction of total smoke condensate, reduction of tumorigenic agents, and reduction of cilia-toxic agents. The chapter also provides an interpretation of experimental findings that include inhalation studies, statistical considerations, future studies, and relation to human data.