Despite decades of research and breakthroughs, the origins of breast and ovarian cancers remain a mystery for 90 percent of women—a huge obstacle to treating these diseases. Imagine if we could predict whether a baby would grow up to develop breast cancer the moment she was born. Now imagine if we could make this prediction before she had even been conceived.
We now know that cancer has its roots in prenatal life.
We’re now a big step closer to that reality. At the end of the 20th century, it was suggested that breast cancer may be initiated before birth. Indeed, in 2006 a study found that breast-cancer risk was higher in girls who were born at the heavy end of the birthweight scale. But it was the Helsinki Birth Cohort of 1934-1944 that allowed more than 6,000 Finnish women to be studied. As part of this study, women had their pelvic measurements recorded at the time they delivered their babies.
Recently, David Barker, Johann Eriksson (University of Finland), and myself, along with our colleagues, decided to revisit these records, now over half a century old. We scrutinized them with an eye toward which of the women had daughters with breast cancer, and found that approximately 300 did.
Breast cancer in the daughters was found to be highly correlated with the width of the mother’s pelvic crest, the distance between the bony ridges that a woman can feel on her hipbones. A woman whose pelvic width was greater than 30 centimeters (about 12 inches) had a risk for cancer that was 1.6 times higher than a woman whose pelvis was less than 28 centimeters (11 inches).
But we also found that the shape—the roundness—of the pelvic crest was a predictor of breast disease in the daughters. So if the front edge of the pelvic ridge grew toward the midline of the woman’s body so that the dimension across the front was 3 centimeters (1.2 inches) shorter than the maximum width of the pelvic bone along the side, the risk for cancer in the daughter was 2.4 times higher than for a woman where the front dimension and the total width were equal.
The risk of breast cancer predicted by hip width was especially increased in babies born too early or too late. The risk of cancer was 2.1 times or 1.6 times higher if a woman was born before 36 weeks or after 40 weeks of gestation, respectively (compared to term at 39 weeks). This effect was very powerful. If a woman was born after 40 weeks and was born to a mother who had more than one child, her risk for breast cancer increased dramatically to 6.7 times the rate of a woman born to a mother with 1 child. The post-term effect may explain, in part, the relationship with high birthweight found in 2006.
Why does maternal hip width predispose to cancer in babies born to that mother? Hip growth during puberty is related to a girl’s estrogen levels which, in turn, are related to her pubertal nutrition. Thus, the estrogen level that determines pelvic growth in a young woman’s body is the same level that imparts risk to her daughter within the first few weeks following conception. It is likely that maternal estrogen exposes the cells in her embryonic daughter that will become breast tissue in later development. This estrogen exposure causes either genetic instability or silences genes that restrain growth of breast tissue. Breast tissue that is exposed to estrogen in the embryo is very vulnerable and more easily transformed into cancer tissue in later life. Further, estrogen or carcinogen exposure over a lifetime leads to the development of cancer. A similar picture can be painted for ovarian cancer.
Thus, we now know that cancer has its roots in prenatal life. In addition, we may find that girls who eat energy-dense foods (ie. foods high in calories per gram, like french fries, burgers, and milkshakes) and put on weight before puberty will have higher estrogen levels at the time when their pelvic bones depend on estrogen signals to regulate their growth and shape. These girls will have wider, rounder hips and will have high estrogen levels for life. High levels could damage sensitive cells in the placenta and breast tissue with life-long consequences for the offspring. The role of genes in causing a predisposition for cancer during this time of life is unknown and warrants intensive research.
Kent L. Thornburg, Ph.D., is a medical scientist who is internationally known for his work on the roots of adult-onset diseases. He is the founding director of the Heart Research Center at the Oregon Health and Science University.