STOCKHOLM-- Genetics has far less influence on the development of most types of cancer--including lung cancer--than the environment does, a new Scandinavian study shows.[1] "We found that genetic factors account for only about 20% to 40% of cancer susceptibility, whereas environmental factors account for about 60% to 80%," reported lead author Paul Lichtenstein, MD, in an interview with RESPIRATORY REVIEWS.

To separate the effects of nature and nurture, the study authors analyzed the pooled data for nearly 45,000 pairs of twins listed in the Swedish, Danish, and Finnish twin registries. "This may be the largest twin study ever performed," said Dr. Lichtenstein, an Associate Professor of Medical Epidemiology at the Karolinska Institute in Stockholm.

The study should help to dispel the common misconception that genetic factors are the main causes of cancer--a myth that arose, said Dr. Lichtenstein, because of all the attention cancer genes have gotten in the media in recent years. The findings should also help to decrease the fear of hereditary cancer among twins and close relatives of cancer patients.

WHY A TWIN STUDY?

By comparing cancer concordance in twin pairs, researchers can estimate the effect of genetics and the environment on the development of cancer. High concordance suggests a strong influence for genetic factors, whereas low concordance indicates a weak influence.

The number of twin pairs in each cancer registry--and the number of patients with cancer--is listed in Table 1. The study authors determined the risk of 28 types of cancer for the twins of cancer victims; they also estimated the importance of genetic and environmental factors in causing 11 of those cancers (Figure 1).

Table 1 Cancer in the Scandinavian Twin Registries
Twin registry	No. of twin pairs	No. of patients with cancer
Swedish	23,386	5,647
Danish	8,461	3,572 *
Finnish	12,941	1,584
* Excludes those with a diagnosis of nonmelanoma skin cancer. Data extracted from Lichtenstein et al. N Engl J Med. 2000.[1]

 

Figure 1 Factors That Influence Susceptibility to Cancer

TYPE OF CANCER

Shared environmental factors are those that both twins would have been exposed to; nonshared environmental factors are those that only one twin would have been exposed to. Courtesy of Paul Lichtenstein, MD.

GENERALLY LOW CONCORDANCE

The study authors identified 10,803 people in 9,512 twin pairs who received a diagnosis of at least one type of cancer. "Overall, the twin of a person with cancer had an increased risk of having the same cancer," they reported. "This was especially evident for cancer of the stomach, colorectum, lung, breast, and prostate."

The likelihood of lung cancer, for example, was nearly eight times greater in a man whose monozygotic twin had lung cancer than in a man whose monozygotic twin did not have lung cancer. However, lung cancer concordance for male monozygotic twins was only 0.11. In other words, the probability was only 11% that the monozygotic twin of a man with lung cancer would also develop lung cancer.

Similarly, a woman whose monozygotic twin had lung cancer had a 25.3 relative risk of developing lung cancer. Yet lung cancer concordance for female monozygotic twins was only 0.09.

In fact, cancer concordance was generally below 0.10. "This suggests that the risk of cancer in a twin or first-degree relative of someone with cancer is relatively modest," Dr. Lichtenstein recently told RESPIRATORY REVIEWS. There were no twin pairs, he added, in which both twins had non-Hodgkin's lymphoma or Hodgkin's disease or cancer of the lip, oral cavity, pharynx, kidney, thyroid, bone, or soft tissue.

Not surprisingly, concordance was generally greater for monozygotic twins than for dizygotic twins. For example, the lung cancer concordance for male dizygotic twins was 0.10; for female dizygotic twins, it was 0.01.

In most cases, the authors' statistical estimates of the influence of genetics and the environment on cancer susceptibility attributed most of the risk to the latter. In lung cancer, for instance, genetic factors accounted for only 26% of the susceptibility versus a combined 74% for shared and nonshared environmental factors.

The estimates of genetic effects were statistically significant only for breast, colorectal, and prostate cancer. For these malignancies, genetic factors contributed 27%, 35%, and 42%, respectively, of the cancer susceptibility. No significant differences emerged between the sexes in the influence of genetics on cancer susceptibility for any of the cancers studied.

ENVIRONMENT PLAYS KEY ROLE

The environment, not heredity, plays the principal role in causing cancer, the authors concluded. "However, our study does provide evidence for continuing the search for cancer genes," said Dr. Lichtenstein, who pointed out that current knowledge of gene mutations does not fully explain the relatively large contribution of genetics to the susceptibility to breast, colorectal, and prostate cancer. "Genetic research will certainly provide us with a greater understanding of the biological mechanisms underlying cancer," he added. "However, it is unlikely that genetic research alone will help us eradicate cancer."

This study has many strengths, especially its large size, the fact that it is population-based, and that its outcomes are derived from complete data on cancer incidence, wrote Robert N. Hoover, MD, in a recent editorial.[2] Despite its size, however, the study effectively addressed only the four or five of the most common cancers, he asserted.

Other limitations are the study's large confidence intervals for the effect of genetics on stomach, colorectal, breast, and lung cancer risk. The study also lacks data on cancer screening practices and specific environmental factors, such as tobacco use. These data are necessary to examine interactions between genes and the environment.

However, such practical limitations are inherent in studies of cancer in twins, acknowledged Dr. Hoover, the Director of the Epidemiology and Biostatistics Program at the National Cancer Institute in Rockville, Maryland. "Despite its limitations, the study by Lichtenstein et al provides new and valuable information for the nature-versus-nurture debate," he emphasized.

--Timothy M. Begany

References
1. Lichtenstein P, Holm NV, Verkasalo PK, et al. Environmental and heritable factors in the causation of cancer. N Engl J Med. 2000;343:78-85.
2. Hoover RN. Cancer--nature, nurture, or both [editorial]. N Engl J Med. 2000;343:135-136./font>