The study of cancer occurrence in twin pairs provides a unique window into the causes of disease. By comparing the diagnoses of twins, researchers can separate the influence of genetics from the effects of shared life experiences. While having a twin with a cancer diagnosis does not guarantee the other twin will also develop the disease, it does signify a measurable elevation in overall risk.
Why Identical and Fraternal Twins Have Different Risk Profiles
Identical twins (monozygotic or MZ) originate from a single fertilized egg, sharing nearly 100% of their DNA. Fraternal twins (dizygotic or DZ) develop from two separate eggs, sharing only about 50% of their DNA, similar to non-twin siblings.
When researchers study cancer in these pairs, they look for concordance—the presence of the disease in both twins. A significantly higher concordance rate in MZ twins compared to DZ twins suggests that genetic inheritance attributes a meaningful portion of the risk. Conversely, if the risk is similar between both pairs, a shared environment or lifestyle is likely the primary contributor. A major study tracking over 200,000 Nordic twin pairs found that if one twin was diagnosed with cancer, the co-twin’s risk of developing any cancer increased by 14% for identical twins, but only 5% for fraternal twins.
Separating Genetic and Shared Environmental Factors
Twin studies partition the overall risk of disease into three components: heritability (the proportion of risk due to genetics), shared environmental factors, and unique environmental factors. Shared environmental factors include elements both twins experience equally, such as early childhood diet or exposure to parental smoking. Unique environmental factors are exposures specific to one twin, like a particular infection or individual sun exposure habits.
Researchers have estimated that the overall heritability for cancer is approximately 33%, meaning that genetic factors account for one-third of the liability for developing the disease. This genetic component primarily involves germline mutations, which are inherited gene changes. These inherited variants increase the baseline susceptibility to cancer by impairing DNA repair or cell growth control mechanisms. In contrast, most cancers are driven by somatic mutations, which are acquired changes that occur later in life in a single cell line and are not inherited or shared by the twin.
The remaining risk is attributed to environmental components, with unique, non-shared exposures accounting for the largest proportion. The twin model provides a statistical framework to understand how inherited risk interacts with the multitude of exposures encountered throughout a lifetime to trigger the disease process.
Cancer Concordance Varies by Type
The risk elevation for a co-twin varies significantly depending on the specific type of cancer. Cancers with a strong inherited component show the highest concordance rates in MZ pairs, reflecting a greater influence of shared DNA. For instance, the heritability of skin melanoma and prostate cancer is high, estimated at 58% and 57%, respectively, indicating a substantial genetic predisposition.
The familial risk for testicular cancer is pronounced, with a man being 28 times more likely to develop it if his identical twin has the diagnosis, compared to the general population. In contrast, common cancers like lung, colon, and rectal cancer show a much lower heritability, suggesting that lifestyle factors such as smoking or diet are the dominant risk drivers. For childhood cancers, such as leukemia, high concordance is observed almost exclusively in identical twins, often attributed to the sharing of blood circulation during development in the womb, allowing for the potential transmission of pre-leukemic cells. Interestingly, when both members of a twin pair develop cancer, they often develop different types, suggesting a shared inherited susceptibility to a general breakdown in cancer-protective mechanisms rather than a predisposition for a single organ-specific disease.