A Mother's Mismatch: Why Cancer Has Deep Evolutionary Roots

Across the tree of life, we can trace cancer vulnerabilities back to the origins of multicellularity.¹ Cancer is observed in almost all multicellular phyla, including lineages leading to plants, fungi, and of course, animals.¹ Even our favorite pre-historic ancestors, the dinosaurs, got cancer.² Broadly, cancer is a consequence of faulty cellular division, creating somatic mutations in DNA that lead to uncontrolled cellular proliferation. These mutations can occur every time a cell divides, increasing chances of mutations as an organism increases in complex multicellular life. Thus, along with the evolution of multicellularity, organisms have co-evolved mechanisms of cancer suppression and prevention.³ These evolutionary forces of cancer defenses are one reason cancer is a disease of aging, hiding in ‘selections shadow’. However, introduction to novel environments may disrupt these cancer defense mechanisms. While cancer is a consequence of our evolutionary machinery, we are seeing higher than expected rates of cancer in human populations, suggesting an environmental component to the risk as well.⁴

A major contribution to high rates of cancer in industrialized societies may be due to evolutionary mismatch. For 99% of human history, we lived in small-scale subsistence populations, hunted and gathered food sources, and had no access to birth control. Recent changes in the environment, such as agriculture, urbanization, domestication, hygiene, and medicine have quickly led western, industrialized populations to be disconnected from our ancestral environment. Consequently, many lifestyle factors in industrialized, large-scale populations may increase the risk for malignancy.⁵

Women in Post-Industrial Societies Have Different Reproductive Profiles

Well-known cancer risk factors in post-industrial humans include smoking, UV exposure, reduced exercise, and increased caloric intake.⁵ Here I will highlight a potentially unfamiliar cancer risk factor for women: ‘modern’ reproductive patterns.⁶ ‘Modern’ reproductive patterns refer to fertility patterns of women in western, industrialized populations. These patterns are characterized by decreased age of menarche, delayed age of first birth, fewer children, and a shorter duration breastfeeding. Consequently, women in western societies have more menstrual cycles and higher cumulative exposure to reproductive hormones, such as estrogen. Reproductive hormones are involved in a variety of cellular mechanisms, including the enhancement of cellular proliferation. Tissues of the reproductive tract may simply be exposed to more cellular growth from chronic exposure to hormones, increasing the risk of reproductive cancers, such as breast and ovarian cancer. Indeed, breast cancer is the most commonly diagnosed cancer in women globally.⁷

How much estrogen are post-industrial women being exposed to? Women living in subsistence populations, such as hunter-gathers and forager-horticulturists, can give us insight into ‘natural’ fertility patterns among humans. In populations without contraceptives, women spend much of their reproductive years being pregnant or in lactational amenorrhea - a postnatal period where breastfeeding suppresses menstruation. It is estimated that women in subsistence populations have 100-150 ovulatory cycles over a lifetime.^8,9 Some would argue there is nothing regular about a monthly menstrual cycle in natural fertility populations.⁹ In contrast, women in the western world are estimated to have 300-400 menstrual cycles during the course of their lifetime, suggesting nearly three times the exposure of reproductive hormones and more opportunities for somatic mutations to occur during cell division.⁹

Lack of Support for Mothers May Exacerbate Reproductive Mismatch

Women’s reproductive profiles in modern industrial societies, such as delayed childbirth, reduced breastfeeding, and smaller families, can contribute to increased exposure to cycling estrogen. However, the lack of support for mothers in modern societies, including high childcare costs, short maternity leaves, and reduced breastfeeding support may exacerbate these issues. There needs to be a focus on how to better support families, especially mothers, and their choice for when to optimally start a family. Women in western populations may delay starting a family and having children for many reasons. Childcare is becoming increasingly expensive, couples may live far from kin networks, and many may choose to become financially stable prior to starting a family. Additionally, continuing education, exams, and starting a career are all factors that may delay a women’s opportunity to have children when she would optimally want them. Further, the period of recovery after giving birth and the difficulties of quickly returning to work may dissuade some women from having additional children. Returning to work promptly after giving birth reduces a mother’s likelihood of prolonged breastfeeding.¹⁰ To support women who do choose to start a family, we should focus on subsidized healthcare, affordable childcare, childcare options at workplaces and school, increased maternity leave, and lactation counseling and support. While cancer is not exclusively a disease of modern environments, many modern environmental changes influence our disease susceptibility. Modifying cultural practices, such as providing additional support for mothers, may help mitigate these costs.

References:

1. Aktipis, C. Athena, Amy M. Boddy, Gunther Jansen, Urszula Hibner, Michael E. Hochberg, Carlo C. Maley, and Gerald S. Wilkinson. "Cancer across the tree of life: cooperation and cheating in multicellularity." Phil. Trans. R. Soc. B 370, no. 1673 (2015): 20140219.

2. Rothschild, Bruce M., Brian J. Witzke, and Israel Hershkovitz. "Metastatic cancer in the Jurassic." The Lancet 354, no. 9176 (1999): 398.

3. Boddy, Amy M., Hanna Kokko, Felix Breden, Gerald S. Wilkinson, and C. Athena Aktipis. "Cancer susceptibility and reproductive trade-offs: a model of the evolution of cancer defences." Phil. Trans. R. Soc. B370, no. 1673 (2015): 20140220.

4. Hochberg, Michael E., and Robert J. Noble. "A framework for how environment contributes to cancer risk." Ecology Letters 20, no. 2 (2017): 117-134.

5. Greaves, Mel. "Nothing in cancer makes sense except…." BMC Biology 16, no. 1 (2018): 22.

6. Aktipis, C., Bruce J. Ellis, Katherine K. Nishimura, and Robert A. Hiatt. "Modern reproductive patterns associated with estrogen receptor positive but not negative breast cancer susceptibility." Evolution, Medicine, and Public Health 2015, no. 1 (2015): 52-74.

7. Ferlay, Jacques, Isabelle Soerjomataram, Rajesh Dikshit, Sultan Eser, Colin Mathers, Marise Rebelo, Donald Maxwell Parkin, David Forman, and Freddie Bray. "Cancer incidence and mortality worldwide: sources, methods and major patterns in GLOBOCAN 2012." International Journal of Cancer 136, no. 5 (2015).

8. Eaton, S. Boyd, Malcolm C. Pike, Roger V. Short, Nancy C. Lee, James Trussell, Robert A. Hatcher, James W. Wood et al. "Women's reproductive cancers in evolutionary context." The Quarterly Review of Biology 69, no. 3 (1994): 353-367.

9. Strassmann, Beverly I. "Menstrual cycling and breast cancer: an evolutionary perspective." Journal of Women's Health 8, no. 2 (1999): 193-202.

10. Ogbuanu, Chinelo, Saundra Glover, Janice Probst, Jihong Liu, and James Hussey. "The effect of maternity leave length and time of return to work on breastfeeding." Pediatrics (2011): peds-2010.

Image: Participants during a breast cancer awareness 5 km run hosted by the Hispanic Heritage Committee at Ramstein Air Base, Germany, Oct. 8, 2016. Photo by Airman 1st Class Savannah L. Waters via Flickr.