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Twins demonstrate significant excess familial risk for cancer
A long-term prospective study of twins from Nordic countries revealed a significant excess familial risk for cancer overall among those whose co-twin was diagnosed with a malignancy.
Results also showed excess risk for several specific cancer types, including prostate cancer, melanoma, breast cancer and ovarian cancer.
“Family-based studies have been helpful in describing familial aggregation of cancer,” Lorelei A. Mucci, ScD, MPH, associate professor of epidemiology at Harvard T.H. Chan School of Public Health, and colleagues wrote. “Large twin studies of cancer can provide further insight into the relative contribution of inherited factors and characterize familial cancer risk by leveraging the genetic relatedness of monozygotic and dizygotic pairs of twins.”
Mucci and colleagues sought to estimate the familial risk and heritability of cancer types in a large cohort of twins from Nordic countries.
The analysis included 203,691 people — 80,309 monozygotic twins and 123,382 same-sex dizygotic twins — within the population-based registers of Denmark, Finland, Norway and Sweden.
Twins were followed for a median of 32 years between 1943 and 2010. The observation of incident cancer served as the primary endpoint.
The researchers identified a total of 27,156 incident cancers diagnosed in 23,980 individuals, equating to a cumulative incidence of 32% in the overall cohort.
Cancer diagnoses in both twins occurred among 1,383 monozygotic pairs and 1,933 dizygotic pairs. Approximately 38% of monozygotic pairs (n = 522) and 26% of dizygotic pairs (n = 496) were diagnosed with the same type of cancer.
The researchers observed an excess cancer risk among twins whose co-twin was diagnosed with cancer.
Compared with the cumulative risk in the overall cohort (32%), dizygotic twins whose co-twin developed cancer had an absolute 5% increased estimated cumulative risk (37%; 95% CI, 36-38), and monozygotic twins whose co-twin developed cancer had an absolute 14% increased estimated cumulative risk (46%; 95% CI, 44-48).
Cancers with the highest estimated cumulative incidence in the cohort included prostate cancer (10.5%), breast cancer (9.4%), lung cancer (3.2%), colon cancer (2.9%) and nonmelanoma skin cancer (1.9%). Although the researchers observed elevated familial risks among monozygotic and dizygotic twins with most cancer types, these risks appeared substantially higher among monozygotic pairs for prostate cancer and breast cancer.
The heritability of cancer overall was 33% (95% CI, 30-37).
Cancer types with significant heritability included melanoma (58%; 95% CI, 43-73), prostate cancer (57%; 95% CI, 51-63), nonmelanoma skin cancer (43%; 95% CI, 26-59), ovarian cancer (39%; 95% CI, 23-55), kidney cancer (38%; 95% CI, 21-55), breast cancer (31%; 95% CI, 11-51) and uterine cancer (27%; 95% CI, 11-43).
The researchers reported a high estimate for shared environmental factors for lung cancer (24%). Conversely, relative to other cancers, heritability estimates for gastrointestinal cancers — specifically cancers of the colon (15%; 95% CI, 0-45), rectum (14%; 95% CI, 0-50) and stomach (22%; 95% CI, 0-55) — appeared smaller.
The median difference in age at diagnosis was slightly shorter among monozygotic twins than dizygotic twins for all cancer cases combined (8 years vs. 9.3 years).
The researchers acknowledged limitations of their study, such as the inability to report data on certain rarer cancer subtypes, including many hematologic malignancies. Further, because the study cohort was primarily white, the findings may not be generalizable to more diverse populations.
“The large number of cancer cases and long follow-up in the cohort allowed us to provide more precise estimates of familial risk and heritability for several malignancies,” Mucci and colleagues wrote. “This information about the hereditary risks for cancers may be helpful in patient education and cancer risk counseling.” – by Cameron Kelsall
Disclosure: One study researcher reports personal fees from and a consultant role with Pfizer. Mucci and the other researchers report no relevant financial disclosures.