Study of twins sheds light on how genetics influences cancer risk

A study of over 200,000 twins followed for a median of 32 years is providing more information about how genetics influences cancer risk.

The study, published Tuesday in the Journal of the American Medical Association, found that cancers of various types run in families. Overall, researchers found that about 33 percent of the population’s variance in cancer risk was due to genetics, but the figure ranged widely for different types of cancer.

Researchers looked at identical and fraternal twins in Denmark, Finland, Norway, and Sweden, who were part of the Nordic Twin Study of Cancer. They determined whether the twins had cancer from national registries. They found that risk of some cancers  notably skin, prostate, ovary, kidney, breast, and uterine cancer  was measurably influenced by genetics.

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These estimates were based on the concept of “heritability.” Heritability is a controversial and widely misunderstood concept. Counterintuitively, it does not mean how much of an individual’s risk of developing cancer comes from genetics as opposed to the environment. It also does not mean how much of the individual’s risk is “inherited” from parents. Instead, it reflects how much genetic differences among people in a specific group account for differences in the risk of cancer within that group.

These results are based on individuals in Nordic countries, and authors caution that they cannot be generalized to other populations.

Other teams have published recent heritability estimates for breast and prostate cancer. A large twin study in 2000 reported heritability estimates for breast, prostate, and colorectal cancer, but this current study has given those findings greater statistical certainty. All of these studies were conducted on individuals from Nordic countries.

“Earlier studies were not critically large enough to be able to provide any information about heritability for [some] cancers,” said Lorelei Mucci, the study’s lead author and an associate professor of epidemiology at the Harvard T.H. Chan School of Public Health. “Our ability to provide information about the relative contribution of genetic factors for these more rare cancers is really important.”

Twin studies are often thought to be able to determine how much genetics contributes to the condition being studied — in this case, incidence of cancer. But this is problematic, critics say, because it rests on many questionable assumptions.

The study’s authors conclude that this information may better inform patients. “This information about hereditary risks of cancers may be helpful in patient education and cancer risk counseling,” they write.

However, the study itself did not address the meaning of “hereditary risk,” which is different from “heritability.”

Evan Charney, an associate professor at Duke University in the Sanford School of Public Policy, said it would be problematic to use information about cancer heritability in discussions with individual patients. Heritability is a population-level property, which can change widely even if the individuals in the population stay exactly the same.

“I think it would be unconscionable and completely unjustified at this point to try to translate the results of a finding like this into risk or probability that a physician would tell a patient,” Charney said.

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