Family History Important in Most Cancers

According to a controversial new study by Stanford University researcher Neil Risch, PhD, family history may be an important risk factor for most, if not all, cancers.

Risch's findings run counter to an earlier study published in the New England Journal of Medicine that pinpointed environment as the primary culprit and downplayed the contribution of genes in the development of the disease.

However, when Risch used a different statistical model to analyze the same data from that previous study, he found that nearly all of the cancers can be passed equally through families. He also showed that cancers that occur early in life are more likely to have a genetic component than cancers diagnosed in later years.

Furthermore, Risch discovered that rare cancers, such as thyroid and testicular cancers, are even more likely to be familial than more common cancers such as those of the breast and lung. He said his results re-emphasize the importance of continuing the search for genes associated with cancer.

"The evidence suggests that inheritance plays a role in most, if not all, cancers," wrote Risch in the journal Cancer Epidemiology, Biomarkers & Prevention. "The conclusions of the previous study are a direct result of the model the researchers selected to analyze the data. If you use an alternate model - one that I think fits the data better - you can come to the conclusion that nearly all cancers have a genetic component," Risch concluded.

Risch analyzed data from the same 45,000 pairs of twins used in the earlier study, which was published in the July 13, 2000, issue of the New England Journal of Medicine. That study assumed most cancers are the result of the additive contributions of many different genes, each of which has only a minimal effect on disease development. The researchers found that when they calculated the relative contributions of genetic and environmental factors to cancer risk, environment nearly always won out.

In contrast, Risch found that the twin data for this and two other large-scale twin studies could be better explained using a statistical model that assumed the cancers were the result of either only one gene, or of several relatively rare genes. The new model led him to a very different conclusion: cancers are genetically influenced.

Risch further concluded that rare cancers are more likely to be inherited than common ones, and cancers with an early onset are more likely to be inherited than those that develop later in life. In other words, a man whose brother develops prostate cancer at a young age is more likely to develop prostate cancer himself.

Risch emphasized that his analysis doesn't rule out the effects of environmental factors. However, it clearly demonstrates the predominate influence of genetic factors in the development of cancer.

SOURCES:
Cancer Epidemiology, Biomarkers & Prevention, July 2001; 10:733-741
New England Journal of Medicine, July 13, 2000; 343:78-85
Stanford University Medical Center (http://www-med.stanford.edu)

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