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Long-term follow-up of risk of cancer among twins

The JAMA Network Journals

In a long-term follow-up study among approximately 200,000 Nordic twin individuals, there was an increased cancer risk in twins whose co-twin was diagnosed with cancer, with an increased risk for cancer overall and for specific types of cancer, including prostate, melanoma, breast, ovary, and uterus, according to a study in the January 5 issue of JAMA.

The global burden of cancer is considerable, with an estimated 12 million new cases and 8 million cancer deaths each year. In 2015 in the United States, 1.7 million individuals will be diagnosed with cancer and 590,000 will die of cancer, accounting for 1 in 4 deaths. Refinement of primary and secondary prevention strategies (i.e., factors that would have the greatest influence on reducing cancer incidence and death) requires a detailed understanding of the contribution of genetic and environmental factors to disease pathogenesis (the origination and development of a disease). Large twin studies of cancer can provide insight into the relative contribution of inherited factors and characterize familial cancer risk (risk of cancer in an individual given a twin's development of cancer) by leveraging the genetic relatedness of monozygotic (twins developed from the same fertilized egg [having the same genetic material]) and dizygotic (twins who develop from two separate fertilized eggs) twins, according to background information in the article.

Lorelei A. Mucci, Sc.D., M.P.H., of the Harvard T. H. Chan School of Public Health, Boston, and colleagues estimated familial risk and heritability (proportion of variance in cancer risk due to interindividual genetic differences) of cancer types among 80,309 monozygotic and 123,382 same-sex dizygotic twin individuals (n = 203,691) from the population-based registers of Denmark, Finland, Norway and Sweden. Twins were followed up a median of 32 years between 1943 and 2010. There were 50,990 individuals who died of any cause, and 3,804 who emigrated and were lost to follow-up.

A total of 27,156 incident cancers were diagnosed in 23,980 individuals, translating to a cumulative incidence of 32 percent. Cancer was diagnosed in both twins among 1,383 monozygotic (2,766 individuals) and 1,933 dizygotic (2,866 individuals) pairs. Of these, 38 percent of monozygotic and 26 percent of dizygotic pairs were diagnosed with the same cancer type. There was an excess cancer risk in twins whose co-twin was diagnosed with cancer, with estimated cumulative risks that were an absolute 5 percent higher in dizygotic (37 percent) and an absolute 14 percent higher in monozygotic twins (46 percent) whose twin also developed cancer compared with the cumulative risk in the overall cohort (32 percent).

For most cancer types, there were significant familial risks and the cumulative risks were higher in monozygotic than dizygotic twins. Heritability of cancer overall was 33 percent. Significant heritability was observed for the cancer types of skin melanoma (58 percent), prostate (57 percent), nonmelanoma skin (43 percent), ovary (39 percent), kidney (38 percent), breast (31 percent), and corpus uteri (a part of the uterus; 27 percent).

"The data provide strong evidence of an excess familial risk for 20 of the 23 cancer types, as shown by the comparison of familial risks for those cancers with the cumulative risk in the twin cohort overall," the authors write.

The researchers note that dizygotic pairs of twins are as genetically similar as siblings, so that familial risk estimates among dizygotic pairs are relevant for siblings who are born at separate times.

"This information about hereditary risks of cancers may be helpful in patient education and cancer risk counseling."

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(doi:10.1001/jama.2015.17703; Available pre-embargo to the media at http://media.jamanetwork.com)

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