Health: Second Opinion

REGULAR cigarette smokers who are honest with themselves must sometimes wonder whether they might get lung cancer. Many take comfort from relatives who have smoked all their lives and escaped the disease. Statistics show that four out of five smokers who reach old age die from something other than lung cancer (although their deaths may still be due to tobacco-related diseases such as coronary heart disease or cancer of the larynx). Why is it a minority of smokers who die from lung cancer? And how can a smoker estimate his or her own risk?

The most likely explanation has always seemed a genetic one. Cancers of the breast and colon, especially those occurring in people under the age of 50, are known to have strong genetic components, some of which have been identified precisely enough to allow division of other family members into high and low-risk categories. For lung cancer, too, there is some evidence that the blood relatives of people with the disease are at increased risk of developing it, but closer examination of the genetic evidence has cast doubt on this belief.

The classic way to discover how much susceptibility to a disease is inherited is to look at twins. Identical (monozygotic, MZ) twins have exactly the same genes, which is why they look alike and often have similar

aptitudes and interests. Non-identical

(dizygotic, DZ) twins are no more alike than any other brother and sister; they have around 50 per cent of their genes in common. So if a disease or susceptibility to it is passed on with the genes it will be found in both twins (concordance) more frequently when they are an identical, MZ pair than when they are non-identical. Both identical twins or neither inherit the family's red hair; and both or neither inherit the family's

tendency to certain diseases.

Not everyone who inherits a tendency to a particular disease goes on to develop it. If sufficient numbers of pairs of twins with and without a disease are studied, however, then a measure can be made of the importance of genetic factors in that disease.

This method was used in a recent Lancet report on lung cancer using data on 15,924 pairs of twins born in the United States between 1917 and 1927. The numbers of pairs of twins who had both died from lung cancer were small - 10 of the MZ pairs and 21 of the DZ pairs. Calculations clearly showed, however, that the concordance rate was lower in the identical twins. 'In our study,' the American researchers concluded, 'there is little if any effect of inherited predisposition on development of lung cancer.'

Why, then, do only some lifelong smokers get the disease - still the leading cause of cancer death in western countries? The best answer that medical research can offer is that the process is random. We know that several different switches need to be turned on before the cancer starts growing: the chance of all the switches being turned on and of the smoker getting lung cancer is higher the younger he or she began to smoke, is higher the more cigarettes smoked, and increases rapidly with age after 50. If people lived long enough, nearly all smokers would probably develop cancer eventually. As it is, most of them escape.