Sometimes Miracles come in Pairs: Twins & Cancer

Is the onset or progression of cancer mainly caused by an inherent genetic predisposition to mutations that a person cannot control? Or are there extraneous factors involved that can change a person’s fate like diet and lifestyle? Or do other factors exist that connect the two hypotheses like epigenetics—the study of lifestyle influenced biological mechanisms that switch genes on and off? Ideally the question remains: what is the balance between nature and nurture in the context of cancer development?

NorTwinCan (Nordic Twin Study of Cancer) funded mainly by the Ellison Foundation seeks to uncover just exactly what is this nature-nurture balance in terms of cancer with the use of twins – individuals that have the same genetic makeup but can development differently based on environmental influencers. This large scale endeavor began 9 years ago in 2008 making it the largest and first ever study/database of its kind and has utilized a very large cohort of over 300,000+ twins worldwide from Denmark, Sweden, Finland, Norway and the US born as far back as 1895 till present. The aim is to investigate the genetic inheritance and the familial risk relative to environmental factors for many cancers – mainly prostate, lung, breast, ovarian, and colon/rectal cancer, and cancer resistance. Data such as cancer incidence, mortality rate with decades of follow up data are collected and statistically analysed. The NorTwinCam team is made of researchers from the National Twin Registries, private academic institutions such as University of Copenhagen and Norwegian Institute of Public Health and Harvard School of Public Health (7).

Most recent published findings from the NorTwinCan database within the past 5 years are:

One study highlights that there a cancer specific role of nature vs nurture in that colorectal cancer seems to have a higher genetic contribution while colon cancer is more environmentally influenced and that twins sharing the same environment are likely to develop both and should undergo personalized screening (1).
Another study showed that familial factors explain almost nearly 50% of the liability to develop breast cancer while the other half is based on environmental factors, and results were similar for pre- and postmenopausal breast cancer showing that hormonal differences are not a large factor (2).
A study showed consistently that for prostate cancer amongst monozygotic and dizygotic twins, the genetic factor has a larger influence for the susceptibility to develop metastatic prostate cancer (3).
One study addressed the hormonal factor in sex specific cancers looking at male co-twins versus female co-twins and uncovered data that suggests that male co-twins which have a higher exposure to prenatal testosterone compared to female co-twins do not have an increased risk of developing sex specific cancer as previously described. The prevailing hypothesis in the hormone-cancer field is that that hormonal exposure during pregnancy influences the predisposed risk of developing sex-specific cancers and this finding debunks that notion (4).
The most recent finding and first to ever been shown is that when a twin sibling is diagnosed with cancer, the risk for the other twin to develop any form of cancer increases drastically even when the twins have grown up in different places; also in twins pairs where both have developed cancer, each twin often develops a completely different type of cancer from each other suggesting that some families have shared higher risk of any type of neoplasm development that is not cancer type specific. Ultimately among the 20+ cancers investigated (both rare – neck, head & testicular and common cancers – breast & lung), there exists an incredibly high inheritable genetic influence (>33% familial risk)5. This attributes to the example of Lily and Bailey Dove (see picture).

Works Cited

Graff, R. E., Möller, S., Passarelli, M. N., Witte, J. S., Skytthe, A., Christensen, K., . . . Hjelmborg, J. B. (2017). Familial Risk and Heritability of Colorectal Cancer in the Nordic Twin Study of Cancer. Clinical Gastroenterology and Hepatology. doi:10.1016/j.cgh.2016.12.041
Moller, S., Mucci, L. A., Harris, J. R., Scheike, T., Holst, K., Halekoh, U., . . . Hjelmborg, J. B. (2015). The Heritability of Breast Cancer among Women in the Nordic Twin Study of Cancer. Cancer Epidemiology Biomarkers & Prevention,25(1), 145-150. doi:10.1158/1055-9965.epi-15-0913
Hjelmborg, J. B., Scheike, T., Holst, K., Skytthe, A., Penney, K. L., Graff, R. E., . . . Mucci, L. A. (2014). The Heritability of Prostate Cancer in the Nordic Twin Study of Cancer. Cancer Epidemiology Biomarkers & Prevention,23(11), 2303-2310. doi:10.1158/1055-9965.epi-13-0568
Ahrenfeldt, L. J., Skytthe, A., Moller, S., Czene, K., Adami, H., Mucci, L. A., . . . Lindahl-Jacobsen, R. (2015). Risk of Sex-Specific Cancers in Opposite-Sex and Same-Sex Twins in Denmark and Sweden. Cancer Epidemiology Biomarkers & Prevention,24(10), 1622-1628. doi:10.1158/1055-9965.epi-15-0317
Mucci, L. A., Hjelmborg, J. B., Harris, J. R., Czene, K., Havelick, D. J., Scheike, T., . . . Kaprio, J. (2016). Familial Risk and Heritability of Cancer Among Twins in Nordic Countries. Jama,315(1), 68-74. doi:10.1001/jama.2015.17703
10-year-old twins fight leukemia together. (n.d.). Retrieved February 23, 2017, from http://www.cnn.com/2015/09/29/health/dove-family-twins-leukemia/
NorTwinCan. (n.d.). Retrieved February 23, 2017, from http://nortwincan.org/about ![endif]--