During a recent forum on genetic factors in breast cancer, two scientists advocated examining Marin County’s Ashkenazi Jewish population for clues to the area’s staggering breast-cancer rate.
One theory is that genetic predisposition combined with environmental factors may play a significant role.
Contrary to popular opinion, genes account for only 5 to 10 percent of cancers. Except in some Ashkenazi Jews. One in 40 Jews from Eastern Europe carries genetic mutations that frighteningly magnify the risk of breast and ovarian cancers, according to Robin Lee, a UCSF genetics counselor.
Lee and New York epidemiologist Kirsten Moysich spoke last month to about 35 people, mostly women concerned about their personal risks, during a program sponsored by Marin Breast Cancer Watch and the Osher Marin Jewish Community Center in the San Rafael center.
Asked how she would solve the mystery of why Marin County women suffer what researchers believe may be the world’s highest breast-cancer rates, Moysich responded that she would look first at the Ashkenazi Jewish contribution. But the total answer probably lies in a pairing of genes and environment, she said.
“It must be very, very scary for the people in this community,” she said. “I can’t see any big chimneys or any blatant environmental exposures. There’s got to be something out there. Maybe our studies have just been too crude. But it’s very possible that there’s something staring you in the face, and we just don’t know.”
As a professor at the Roswell Park Cancer Institute in Buffalo, Moysich researches the intermingled relationships among genes, environment and cancer. She has teased out proof that toxins once dismissed as unrelated to breast cancer indeed heighten risk.
When scientists initially examined cigarette smoking and breast cancer, for example, they found no association. But a recent study broke out women who smoked the most and who carried a certain genotype. Those women had four times the breast-cancer risk. Research into polychlorinated biphenyls or PCBs, used as coolants and lubricants in electrical equipment, yielded similar results.
Lee said Marin County’s Jewish population “could be one factor” among a host of factors catapulting the breast-cancer rate to 230 per 100,000 in white women in 1999 in a county that would prefer to be known for its hot tubs and hiking trails.
No one can say exactly how many Ashkenazi Jewish women live in the largely affluent county. The 2001 American Jewish Yearbook estimates 18,500 of Marin County’s 250,000 residents consider themselves Jewish.
Some genetic mutations, like the one for Huntington’s disease, guarantee that carriers will fall victim to an illness. But carrying the BRCA 1 and BRCA 2 genes — genes identified with cancer — does not mandate a cancer sentence. It means a lifetime breast-cancer risk of 50 to 85 percent and an ovarian cancer risk of 10 to 45 percent, Lee said.
While being an Ashkenazi Jew is one of many risk factors, Lee said Jews without family histories of cancer do not need to consider getting tested for BRCA genes.
Other risk factors include a family history of male breast cancer, ovarian cancer and multiple cases of premenopausal breast cancer. Paternal family history counts as much as maternal history, Lee said, adding that women have a 50-50 chance of inheriting a BRCA chromosome from either parent.
Testing that turns out negative can alleviate fears. Positive testing can lead to more aggressive screening and other prevention strategies, including removing the carrier’s ovaries and breasts. Some doctors recommend that BRCA carriers remove their ovaries after they are finished bearing children, Lee said. Removal of the ovaries is believed to protect women against breast as well as ovarian cancer.
“I just have to stress there is so much we don’t know,” Lee added.
What is known is that Ashkenazi Jews are vulnerable to a number of diseases, including Tay-Sachs, as a result of mating in a relatively small gene pool. Jews wandered, Lee said, but they wandered together. Scientists also have studied the Jewish population extensively, increasing the body of knowledge about genetic factors.
The pairing of investigations into genes and environmental factors promises to further the knowledge base, according to Moysich.
Moysich studied PCBs in about 900 New York women. When she looked at PCB levels alone, she found no relationship between high levels and breast cancer. However, women with a problematic genotype and high PCB levels had a three-fold breast-cancer risk.
“In molecular epidemiology, we are opening up this black box, and we want to look at diseases in two groups,” Moysich said. In one group are those genetically susceptible to the disease and exposed to the possible toxin, and in the other group are those not genetically susceptible but exposed. “If we combine them, we might muddy the waters and not see the association we expect.”