The prenatal origins of lung cancer. II. The placenta.

We have shown that people who were short at birth in relation to their weight are at increased risk of lung cancer. We suggested that this reflected low amino acid-high glucose delivery to the fetus and that this impaired the development of its antioxidant systems and made it vulnerable to tobacco smoke and other carcinogens in later life. Transfer of amino acids and glucose from mother to fetus depends on the placenta. We here examine how maternal and placental size are related to lung cancer. We studied two cohorts, totaling 20,431 people, born in Helsinki during 1924-1944. Their body size at birth and maternal body size had been recorded together with the weight of the placenta and two diameters of its surface. Of them, 385 had developed lung cancer. Three different maternal-placental-fetal phenotypes were associated with lung cancer. Common to each was a short mother and a newborn baby that was short in relation to its weight. Lung cancer was associated with either a small or a large placental surface area. In the three phenotypes, the hazard ratios associated with a 100 cm(2) increase in placental surface were 0.36 (95% CI 0.14 to 0.87, P = 0.02), 2.31 (1.45 to 3.69, P < 0.001) and 2.04 (1.08 to 3.86, P = 0.03). We conclude that three different maternal-placental phenotypes were associated with later lung cancer. We suggest that each led to low amino acid-normal glucose transfer to the fetus, reflected in a newborn baby that was short in relation to its weight.