Fat Baby Girls and Breast Cancer

We all know two things that affect our health as adults: how we live our lives (diet, exercise, stress reduction, exposure to toxic compounds and the like) and the genetic endowment we got from our parents (genes that raise the risk of cancer, for instance). But over the last few years scientists have begun to recognize a third factor: conditions in the womb during our nine months of gestation.

Now comes more support for this idea. In a new study published today in PLoS Medicine, scientists report that birth size, and in particular birth length, correlates with a woman’s risk of breast cancer in adulthood.

Birth size has long been recognized as a marker of the prenatal environment. In 1999 I wrote the first article in a general publication about the role that the prenatal environment plays in people’s risk of “adult-onset” disorders such as heart disease, stroke, cancer, diabetes and other diseases that we think of as the product of genes or (postnatal) environment. As I said at the time, “The health we enjoy throughout our lives is determined to a large extent by the conditions in which we developed, [conditions that] can program how our liver, heart, kidneys and especially our brain function. It is no exaggeration to call these findings a revolution in the making. The discovery of how conditions in the womb influence the risk of adult disease casts doubt on how much genes contribute to disease (because what scientists classify as a genetic influence may instead reflect gestational conditions) and suggests that adult illnesses long blamed on years of living dangerously (like dining on pizza and cupcakes) instead reflect ‘fetal programming.’ ‘Two years ago no one was even thinking about this,’ says Dr. Matthew Gillman of Harvard Medical School. ‘But now what we are seeing is nothing short of a new paradigm in public health.’"

That paradigm has gotten stronger. In the new study, scientists led by Isabel dos Santos Silva of the London School of Hygiene & Tropical Medicine examined 32 previous studies on the correlation between birth size and breast cancer. That gave them 22,058 cases of breast cancer from a pool of more than 600,000 women. Their conclusion: birth weight is positively associated with breast cancer risk in studies where information on birth size was based on birth records (not in those based on adult self-reports, which are less accurate).

Specifically, every 0.5 kg (about 1 pound) increment in birth weight was associated with about a statistically-significant 7% increase in the risk of breast cancer. Relative to women who weighed 6.6 to 7.7 pounds at birth, those who weighed 8.8 pounds had a 12% greater risk of developing breast cancer. Birth length and head circumference were also associated with an elevated risk: for body length at birth, for instance, the incidence of breast cancer by age 80 is 10%, 10%, 10.4% and 11.5% in those who were in the bottom, second, third and top quarters of birth length, respectively. In other words, the longest baby girls had a 15% greater risk, but that still put them at only 11.5% compared to 10%.

That is certainly not huge. (It’s comparable to the increased risk of breast cancer from drinking alcohol.) Nevertheless, “our study indicates that birth size is a marker of susceptibility to breast cancer in adulthood,” dos Santos said. “The birth size-breast cancer association appeared to be largely independent of known risk factors,” such as diet, pregnancy and nursing. And the association with birth weight held up even after the scientists made statistical adjustments for the woman’s body-mass index in adulthood (obesity is a risk factor for breast cancer), for her mother’s size and other possibly confounding factors. In all, the scientists estimate, large size at birth accounts for about 5% of breast cancers in the U.S. and other developed countries.

In an expert commentary on the study, Pagona Lagiou and Dimitrios Trichopoulos of Harvard University School of Public Health write that it provides “the strongest evidence yet that birth size is a critical determinant of breast cancer risk in adult life.” (Trichopoulos, way back in 1990, suggested that a baby girls’ size at birth might affect her risk of developing breast cancer as an adult, reasoning that in utero exposure to estrogen—which promotes growth—might also primate breast tissue to make it more likely to develop cancer.)

The study is interesting not because it identified a big risk of breast cancer—it did not—but because it raises a question that may be relevant to other ways that breast cancer develops: What the heck can birth size have to do with getting breast cancer decades later? Levels of such growth factors as insulin-like growth factors, leptin, adiponectin and alpha-phetoprotein are all reported to be associated with birth size. These and other hormones “may alter programming of the breast, making it more susceptible to cancer initiation by endogenous hormone levels and other carcinogens later in life,” the scientists explain. The altered programming may involve changes in which genes are turned on and which are silenced. Especially if the altered genes are involved in cell proliferation, survival and differentiation. These changes are likely to occur in the fetal mammary stem cells that give rise to breast cells.