Environment Blamed for Majority of Tumors

BY Rick Weiss
Washington Post, July 13, 2000

The vast majority of cancers are caused not by inherited defects in people's genes, as many believe in this age of genetics, but by environmental and behavioral factors such as chemical pollutants and unhealthy living, according to the largest cancer study ever to enter the "nature vs. nurture'' debate.

"Environmental factors are more important than gene factors, and that's important to remember, especially since everyone thinks that everything is solved now that we have the human genome in our computers,'' said Paul Lichtenstein of the Karolinska Institute in Stockholm, who led the study of 89,576 twins reported in today's issue of the New England Journal of Medicine.

Scientists have long recognized that environmental factors play a notable role in many cancers. People from rural Asia, where breast and colon cancers are rare, gradually grow more likely to get those diseases after moving to the United States -- apparently the result of mostly unidentified environmental factors. People from Japan, where stomach cancer is common, see the risk of that disease decline after living in the United States for several years.

Nevertheless, the environmental contribution to cancer overall has been presumed by many experts to be as low as 50 percent. With the current revolution in molecular biology, much of the search for the causes of cancer has focused recently on genes.

To assess genetic and environmental contributions with unprecedented precision, Lichtenstein and co-workers from Finland and Denmark used detailed government records from their countries to compare the incidence of 28 different kinds of cancer in identical and non-identical twins born between 1870 and 1958. Identical twins share the same genes while non-identical twins, on average, are just 50 percent genetically identical -- the same level of relationship between most siblings and between parents and their offspring.

For every individual who had a cancer, the team checked whether his or her twin ever had the same kind of cancer. The difference between the identical and non-identical twins gave a measure of the extent to which genes were to blame for each kind of cancer.

On average, environmental factors caused about twice as many cancers as inborn genetic factors. The study did not identify what exactly in the environment put people at risk for specific kinds of cancer, but researchers said cigarettes, poor diet, lack of exercise, radiation and pollution were among the prime culprits. Prostate cancer had the strongest genetic component, accounting for 42 percent of the risk, followed by colorectal (35 percent) and breast cancer (27 percent).

"In the current climate, there is this sense of fatalism on the part
of the public with respect to genes. If your brother or mother has
cancer, then you feel doomed,'' said Robert N. Hoover of the National Cancer Institute. But the new data shows that even an identical twin has about a 90 percent chance of not getting the same cancer as his or her affected twin, Hoover said. "I think that's a useful piece of information from this study, to get away from this fatalism.''

The study's authors noted, however, that even if just a third of the
cancer risk is attributable to genetic makeup, that is still a significant percentage, especially for evaluating the risk of prostate cancer.

Some scholars noted that the few genes that so far have been clearly linked to cancer account for just a small fraction of the 20 to 40 percent genetic contribution seen in the new study. That suggests many cancer-susceptibility genes are yet to be found -- and that each probably contributes a small amount of risk to an individual, and so may be difficult to discover.

"This raises the question of why aren't we doing more to identify
avoidable risk factors for cancer, including occupational exposures,'' said Devra Lee Davis, a cancer epidemiologist at Carnegie Mellon University in Pittsburgh. "You can't choose your parents. What you can do is control your exposures in your environment.''

But geneticists said they see a glass one-third full, not two-thirds
empty.

"It's certainly true that if you're in a deterministic camp, and many people have been migrating in that direction lately, it gives pause to see that . . . cancer is not hard-wired in the genes,'' said Francis Collins, chief of the National Human Genome Research Institute. "But that should not make people believe that the genetic approach is not going to be useful. It's going to be incredibly useful. There's a whole iceberg here of more modest individual (genetic) contributions, which account for many cases of cancer.''

Collins emphasized that all cancers are ultimately genetic in nature, since they all are caused by cells whose genes have become disrupted, either by inherited or acquired mutations. Thus, gene studies promise to shed important light on the basic mechanisms of cancer.