Thus, CRC “has a substantial heritable component, and may be more heritable in women than men,” Rebecca E. Graff, ScD, of the Harvard T.H. Chan School of Public Health, Boston, and the University of California, San Francisco, and her colleagues wrote. “Siblings, and particularly monozygotic cotwins, of individuals with colon or rectal cancer should consider personalized screening,” they added.
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The model that best fits the data accounted for additive genetic and environmental effects, the researchers said. Based on this model, genetic factors explained about 40% (95% CI, 33%-48%) of variation in the risk of CRC. Thus, the heritability of CRC was about 40%. The estimated heritability of colon cancer was 16% and that of rectal cancer was 15%, but confidence intervals were wide, ranging from 0% to 47% or 50%, respectively. Individual environmental factors accounted for most of the remaining risk of colon and rectal cancers.
“Heritability was greater among women than men and greatest when colorectal cancer combining all subsites together was analyzed,” the researchers noted. Monozygotic twins of CRC patients were at greater risk of both colon and rectal cancers than were same-sex dizygotic twins, indicating that both types of cancer might share inherited genetic risk factors, they added. Variants identified by genomewide association studies “do not come close to accounting for the disease’s heritability,” but, in the meantime, twins of affected cotwins “might benefit particularly from diligent screening, given their excess risk relative to the general population.”
Funders included the Ellison Foundation, the Odense University Hospital AgeCare program, the Academy of Finland, and US BioSHaRE-EU, and the European Union’s Seventh Framework Programme, BioSHaRE-EU, the Swedish Ministry for Higher Education, and the Karolinska Institutet, and the National Cancer Institute. Dr. Graff had no conflicts of interest.