In the largest medical study ever of twins, Scandinavian researchers have confirmed that environment far outweighs heredity as a risk factor for most cancers. But the study, published in the 13 July issue of The New England Journal of Medicine, also reveals that genes play a greater role than previously thought in three common forms of cancer.
To tease apart a disorder's environmental and genetic roots, researchers can study how often it shows up in both members of pairs of twins (a phenomenon called concordance). Monozygotic or identical twins share all their genes, while dizygotic or fraternal twins share only about half. Thus, a disease caused solely or partly by faulty genes will exhibit higher concordance among monozygotic than dizygotic twins; for diseases caused by environmental factors (such as smoking, workplace exposure, or viral infections), concordance will be lower, and almost equal in both kinds of twins. Most diseases fall between these extremes, and concordance will vary depending on whether environment or heredity has the upper hand.
A scarcity of twins usually limits such studies to all but the most common disorders. So when researchers in Denmark, Sweden, and Finland wanted to study cancer, they combined data from their countries' comprehensive twin and disease registries (some dating back to 1870), forming a massive pool of almost 45,000 twin pairs. Among these, the scientists found a single twin with cancer in about 18% of all pairs, while both twins had cancer in about 3% of pairs--a total of nearly 11,000 people.
Using these figures, the team calculated that genes had the largest influence in breast, colorectal, and prostate cancer, where they accounted for 27%, 35%, and 42% of the total risk, respectively. Nine of the other cancers found, including lymphomas, lip, and thyroid cancer, showed no concordance, a sign that they're primarily induced by unshared environmental factors.
Among the study's discoveries is a piece of good news for twins, says genetic epidemiologist Niels V. Holm of the University of Southern Denmark in Odense, who led the Danish team: Even the highest rate of concordance--found for prostate cancer in monozygotic twins--was only 18%. That means that when one twin gets cancer, the risk to the other sibling is relatively low, says Holm.
The magnitude of the study is "remarkable," says Stephen Gruber, a cancer geneticist at the University of Michigan, Ann Arbor, who says he's surprised by the large genetic influence over some of the most common types of cancer. The results "make it pretty clear that we don't know as much as we thought we did," says Gruber.