Background: Family history is a strong risk factor for colorectal cancer, but the extent to which familial risk can be attributed to heritability versus shared environment remains obscure. Whether familial risk is distinct for colon versus rectal cancer also remains unclear and is important to examine given accumulating evidence that their etiologies are distinct.

Methods: We estimated the concordance and heritability of colorectal, colon and rectal cancer using information from 40,634 monozygotic and 111,897 dizygotic twin pairs from the Nordic Twin Study of Cancer. Time-to-event analyses accounted for left-censoring due to variable initiation of cancer registration and right-censoring resulting from end of follow-up or competing risk of death.

Results: From earliest cancer registration in 1943 through 2009, 2,286 twins were diagnosed with colon cancer and 1,493 were diagnosed with rectal cancer. The cumulative risk of colorectal cancer overall was 4.5%, while the cumulative risk for twins whose co-twins had colorectal cancer was 15.7% for monozygotic and 11.0% for dizygotic twins. The heritability of colon cancer was 16.2% (95% CI: 2.3%-61.8%), with shared environment accounting for 14.2% (95% CI: 2.7%-49.1%) of the variation in disease liability. For rectal cancer, a model including only environmental effects best fit the data; heritability was not statistically important. Shared environment accounted for 16.6% (95% CI: 8.8%-28.8%) of the variation in liability.

Conclusions: These results suggest a greater genetic contribution to the risk of colon cancer than the risk of rectal cancer. The contribution of shared environment to both cancers may be larger than previously thought.

Citation Format: Rebecca E. Graff, Axel Skytthe, Hans-Olov Adami, Kamila Czene, Jennifer R. Harris, Jaakko Kaprio, Edward Giovannucci, Lorelei A. Mucci, Jacob B. Hjelmborg. The heritability of colorectal cancer in the Nordic Twin Study of Cancer (NorTwinCan). [abstract]. In: Proceedings of the Twelfth Annual AACR International Conference on Frontiers in Cancer Prevention Research; 2013 Oct 27-30; National Harbor, MD. Philadelphia (PA): AACR; Can Prev Res 2013;6(11 Suppl): Abstract nr A51.