Despite what you may have been led to believe, the rise in the incidence of breast cancer in the last 80 years is apparently not due to hereditary factors!
In my initial blog post, I discussed Angelina Jolie’s recent decision to undergo a prophylactic bilateral mastectomy because she was a BRCA1 gene carrier. While many questioned her need for such a drastic approach to prevention, in light of her strong family history and her lifetime cancer risk, it was an understandable and well thought out choice. In this follow-up post, I want to elaborate on an important issue that I had previously raised and feel has been both overlooked and/or misunderstood by the media and many doctors. Simply stated, the dramatic rise in the incidence of breast cancer over the last 80 years has occurred in both the carriers of such breast cancer genes and in all women, in general, in western countries. How can I make such a bold statement?
As is often the case in scientific inquiry, during the course of my research on breast cancer risks, I stumbled upon an intriguing and unexpected finding.
Let me explain.
One issue that has always intrigued me is why certain ethnic groups have a markedly lower rate of breast cancer than other ethnic groups. The Inuit of Greenland, along with Eskimo populations in Alaska and Northern Canada, had historically been at a very low risk for most “western diseases” such as cardiovascular disease, diabetes and cancer, including breast cancer. Since I am also very interested in the interplay between cancer and nutrition, I was particularly curious about this ethnic population, because they have very unique dietary habits as a result of their unique and austere environment. I was surprised to discover research indicating the high frequency (1.6%) of a unique BRCA1 mutation, (pCys39Gly) in the Inuits of Greenland, perhaps the highest frequency of any population. This is almost double the frequency of the mutations in Ashkenazi Jewish women, who are perhaps the best-known population at high risk for inherited breast cancer and who actually formed the original population where this inherited gene mutation was identified!
I began to feel like I might really be onto something. However, as I reviewed the data, I was struck by another fascinating parallel. I was in for another surprise. The research indicated that Inuit and Eskimo women currently carrying this mutation have a markedly higher risk of both breast and ovarian cancer than women from the same ethnic population born many decades earlier. The same is true for Ashkenazi women. Their most common gene mutation (185 del AG) is found in 1% of this group. We know that these gene mutations have been present at this frequency for hundreds of years. The likelihood of Ashkenazi mutation carriers born in the 1920s developing breast cancer is between 20 and 30%. This is far less than the current risk of breast cancer for Ashkenazi gene mutation carriers born after the 1940s (up to 85%) and ovarian cancer (50-55% by age 70).
Looking further, other high-risk populations have seen the same rise in risk among mutation carriers in the last 80 years. In Icelandic women, a BRCA2 mutation (999del5) is the leading cause of hereditary breast cancer. For women carriers, in 2002, the lifetime risk for breast cancer was 72% by age 70 but only 18% in 1920, a 4-fold increase in risk. This increase in risk over these years parallels a similar increase in breast cancer risk in all Icelandic women, up to a 4.2X increase in frequency.
What all of these women share is a strikingly higher chance of getting breast cancer now than their female relatives did two or more generations earlier. What they also share is being born during a time in history in which the world was becoming more “westernized” at a rapid rate. The most important issue this raises is what is it about our lifestyle that has raised the risk of breast cancer to these higher levels and what clue will this provide about the origins of breast cancer?
The key issues of the role of the environment and our lifestyle on the increased incidence of breast cancer – what I collectively refer to as “environmental factors” – on both carriers of gene mutations and women in general, how we define environment as cancer researchers, and how the public understands this will be addressed in further posts. Stay tuned.