Study Ties Most Cancer to Lifestyle, Not Genetics
Cancer, for all of the modern emphasis on genes, is largely determined by life, not inheritance, and thus may in most cases be preventable, according to a huge study--the largest of its type--of tens of thousands of twins.
The report, published today in the New England Journal of Medicine, doesn’t negate the influence of genes, finding that they too play significant roles, especially in the cases of prostate and colorectal cancer.
But it underscores the conclusion that comes from a host of other studies: many cancers can be avoided by healthy lifestyle choices such as eating a good diet, exercising and eschewing tobacco.
“I think there is this kind of fatalistic approach to genes that the general public seems to have now--that if your mom, dad, sister or brother had something that you’re doomed to have it too,” said Dr. Robert N. Hoover, director of the epidemiology and biostatistics program at the National Cancer Institute in Bethesda, Md., who wrote a commentary accompanying the report.
In fact, he said, although there are indeed genes that cause high rates of cancer in some families, such fatalism, for the most part, is not warranted.
Overall, genetic factors seemed to account for 21% to 42% of risk, depending on the type of cancer, with an average of about 30%.
The rest of the risk was chalked up to “environmental” factors--a broad category encompassing such influences as experiences in the womb, one’s upbringing and smoking, drinking and eating habits.
The researchers and other experts noted, however, that it is still important for people to pay attention to their family histories, because even a 30% genetic influence on cancer is sizable.
The study, conducted by scientists from Sweden, Denmark and Finland, drew on a treasured genetic resource to reach its conclusions: extensive twin registries in the three nations that permitted the authors to study 44,788 pairs of twins born from 1870 to 1958. Cancer registries revealed that 10,803 of these people developed cancer.
To tease apart the relative contribution of genes versus environment, the scientists compared cancers in identical twins to nonidentical, or fraternal, twins.
Identical twins share the same set of genes, while fraternal twins share only half their genes on average. Thus, if a particular cancer is largely caused by genes, identical twins would be much more likely than fraternal twins to have the same illness. By contrast, if environment is the main cause, then identical and fraternal twins would have about the same cancer risk.
Even when an identical twin had a cancer, the scientists point out, the chance that the other twin got that cancer as well was very low.
The authors caution that they were only able to reach firm or reasonably firm conclusions about the most common cancers--breast, colorectal, prostate, stomach and lung--because the cancer registry data weren’t complete, and even with such a huge sample of twins, the numbers of rarer cancers were too small to yield significant results.
But Paul Lichtenstein, associate professor of genetic epidemiology at the Karolinska Institute in Stockholm, Sweden, and lead author of the paper, said he thinks it’s likely that many rarer cancers will follow similar patterns.
The large influence of environment and lifestyle observed in this and other studies flies in the face of a gene-centric mood in the general public fostered in part by the frenzy surrounding the recently announced mapping of most of the human genetic code, Lichtenstein said.
“I think it is important to say that even though the genome project has a lot of promises for us and for the treatment of cancer and other diseases, it won’t explain all cancers,” he said. “It will not be a miracle and solve all problems.”
Dr. Thomas Mack, professor of preventive medicine at the Keck School of Medicine at USC, called the study “a good paper--it was done very well.”
Although there are definitely genetic differences and lifestyle differences between Scandinavia and the United States, his own, U.S.-based twin research has reached similar conclusions, Mack said.
Among the cancers reliably examined, prostate cancer had the highest rate of heritability--42%. This does not come as a surprise, experts say. An earlier study suggested that this cancer runs more strongly in families than colon or breast cancer, said Dr. Patrick Walsh, chief of urology at the Johns Hopkins Medical Institutions in Baltimore. Thus, he said, it’s particularly important that men ascertain their family history for this disease and be screened if necessary.
So far, while several prostate cancer genes have been located, attempts to pin down environmental causes have yielded little.
This is in stark contrast to other cancers, where--although much is still unknown, and results are often contradictory--a host of studies have pointed fingers at environmental influences.
Smoking, for instance, is linked to not only lung cancer, but to cancers of the stomach, mouth and more. Infection with human papillomavirus increases risk for cervical cancer. A woman’s lifetime exposure to estrogen, as well as exercise, seems to influence her risk for breast cancer. Physical activity, amount of red meat, fruits and vegetables and other aspects of the diet have been implicated in colorectal cancer, and others.
Even a 30% genetic contribution to cancer can in no way be explained by the handful of cancer genes thus far identified, the researchers and other experts pointed out. That indicates that many more cancer susceptibility genes, probably with small effects individually, must be lurking still undiscovered in the genome.
“We have a big gap out there,” said Heather Spencer Feigelson, senior epidemiologist with the American Cancer Society in Atlanta.
Many of those genes will probably affect how we respond to our environment--such as how well our bodies withstand the assault of a pack of cigarettes a day or how well we can reap the benefits of anti-cancer chemicals in the broccoli we eat, says Mack. Figuring out these complicated interactions is a huge goal of the future, experts say.
