*Article: The search for the cause of cancer of the lung
- From: robbb <shek@xxxxxxxxxxxxxxxxxxxxxxxxx>
- Date: Mon, 01 May 2006 22:49:11 GMT
A 37-YEAR-OLD MALE slips on an icy sidewalk, falls, and fractures his wrist. It does not take a collegium of scientists to declare that the bone injury was caused by the fall. Certainly there may have been mitigating or contributory factors: Had he worn thicker clothing, it might have lessened the impact and thus prevented the fracture. Or he may have had three martinis, upsetting his balance. Or a pre-existing osteoporosis may have converted a bone bruise into a fracture. But the fundamental cause, whether enhanced or constrained, was the fall.
With most diseases, however, the relationship between cause and effect is not patently clear.
The ancient Greeks selected a word that became our etiology to define those precursor factors culminating in disease. But medicine first had to accept the difficult notion that diseases, like other physical phenomena, do not arise in a vacuum. Hippocratic writings some 24 centuries ago taught that changes in the weather, diet, occupation, and way of living might cause certain illnesses -- a notable advance over the belief that diseases were little more than expressions of divine judgment.
Then, in the 17th Century, the Italian physician Giovanni Morgagni wrote a seminal text, On the Seats and Causes of Human Disease, a phenomenal book that correlated underlying changes in the internal organs with subsequent human disease.
Yet with all of the great advances in fathoming the etiology of human disease, many illnesses (and certainly such major ones as cancer and cardiovascular disease) remained unexplained well into the 20th Century.
Consider, for example, lung cancer. It was an uncommon cancer in the 19th Century. By the 1940s, though, the lungs surpassed all other organs as sites of cancer. Many theories were proposed for this increased frequency, but without tangible proof of causality, the etiology of lung cancer remained a mystery.
There were, however, some intriguing hints. For example, lung cancer was comparatively common among coal miners, while it remained unknown in rural African village populations. Furthermore, it was quite rare in two American religious groups, the Seventh-Day Adventists and the Mormons; was it the moral rectitude of their adherents or merely that smoking was strongly discouraged within these sects?
Those concerned with the rising epidemic of lung cancer after World War II, particularly in males, were convinced that the cause would prove cumulative, taking years if not decades of exposure to evolve into a cancer. The relationship, therefore, between the cause (then unknown) and the effect (lung cancer) would certainly be hidden within a tapestry of false leads and irrelevant exposures.
Answers were sought to this question: What had the victims of lung cancer been doing for the last few decades that distinguished them from people who did not develop lung cancer?
Two British physicians, Richard Doll and A. Bradford Hill, searched for some compelling etiological relationship in the struggle to identify the cause of lung cancer -- rapidly becoming a major mortality factor in both men and women. And on Oct. 31, 1951, they submitted a questionnaire to the 59,600 physicians listed in Britain's Medical Register. They received 41,024 usable replies (a 68.8-percent response rate).
Beyond the demographic questions, three others were asked: Do you smoke? Have you smoked in the past but given it up? Have you never smoked?
Those who smoked, in the present or past, were then asked at what age their smoking had begun; when it had ended; and the form and quantity of tobacco smoked per day.
Doctors Doll and Hill then assembled the data according to gender, age, amount of tobacco smoked and type of smoking (cigarette, cigar or pipe). And over the next five years they recorded the deaths and causes of death in each category.
By 1954, there were clear hints arising from the accumulating death-registry information. But it was not until 1956 that the data (based on the causes of death in 1,854 survey respondents who had died during the five-year observation) proved statistically conclusive. And on Nov. 10, 1956, Doll and Hill published a famous paper in the British Medical Journal showing a clear etiological relationship between cigarette smoking and lung cancer.
Analysis of their data showed that the death rate from all causes among nonsmokers was 13.3 deaths per thousand per year; and among smokers, 18.8 per thousand per year. Deaths secondary to respiratory disease (such as emphysema) and from coronary thrombosis were substantially more common in the smoker category, but particularly among cigarette smokers, as contrasted with pipe smokers and nonsmokers.
Of the many causes analyzed, it was cigarette smoking that demonstrated the closest numerical relationship with lung cancer. Thus, among nonsmokers the death rate for lung cancer was quite small; among light cigarette smokers, it was about sixfold greater; and among those smoking the equivalent of one or more cigarette packs a day, there was a 23-fold increase.
The Doll and Hill scientific paper is a masterpiece of clarity and meticulous reasoning. The various forms of demographic bias that might distort statistical surveys were carefully addressed before cigarette smoking was finally indicted as a major cause of lung cancer.
Doll and Hill's discussion cites other observations of chronic exposure to toxic agents culminating in cancers: augmented rates of bladder cancer in chemical workers exposed to naphthylamine, and exposure to asbestos resulting in certain forms of lung cancer.
In general, the shorter the interval between a cause and its effect, the easier will be its etiological identification. On the other hand, the subtle relationship between a mother's diet and subsequent developmental anomalies in her offspring, or the relationship between smoking and lung cancer, required years of extensive epidemiological inquiry before they were clarified.
Source: The Providence Journal, Stanley M. Aronson, M.D.- dean of medicine emeritus at Brown University.
--
"Problems are only opportunities with thorns on them." ~Hugh Miller
~DOF + 3M www.ciggyfree.com/info.htm
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