The prenatal origins of lung cancer. I. The fetus.

People differ in their susceptibility to developing cancer on exposure to carcinogens such as tobacco. What causes this is largely unknown. One possibility is that it is determined by nutritional influences during development that permanently change the structure and function of the baby's body. We studied an older and a younger cohort, totaling 20,431 men and women, born in Helsinki during 1924-1933 and 1934-1944. Their body size at birth had been recorded. Of them, 385 had developed lung cancer. Smoking history was known for 6,822 people. At birth, babies who later developed lung cancer had a high ponderal index (birthweight/length(3)). This association was confined to people whose mother's height was below the median. Among these people in the older cohort, the hazard ratio associated with a ponderal index >30 kg/m(3) was 3.1 (95% CI 1.6-5.9), in comparison to those with a ponderal index of 26 kg/m(3) or less (P for trend < 0.001). The equivalent figures for the younger cohort were 2.9 (1.2-7.0, P for trend = 0.001) and this association was independent of smoking. We suggest that a high ponderal index in babies born to short mothers is the result of low amino acid delivery to the fetus in relation to glucose delivery. We hypothesize that this impairs the development of the babies' antioxidant systems and makes them vulnerable to oxidative stress in later life. This is the first evidence that fetal programming may determine vulnerability to carcinogens in humans.