Search for Genetic Clues to Breast Cancer in Hispanic Women

By Jeffrey Norris

Hispanic women in the US are less likely to get breast cancer than non-Hispanic, white women. But it’s not clear why. And despite the lower incidence, breast cancer is still the most common cancer in Hispanic women. For all women, both genes and environment are believed to play a role in breast cancer. It has proved elusive to identify common but subtle genetic influences on breast cancer risk, although more-powerfully-acting mutations in genes known as BCRA1 and BCRA2 have been discovered to play a role in a small minority of breast cancers. With the help of Hispanic women — and their DNA — UCSF physician and researcher Elad Ziv, MD, andpostdoctoral researcher Laura Fejerman, PhD, are looking more deeply into the genetic side of the breast cancer equation. It seems odd, but it actually makes sense to look for genetic risks for breast cancer in Hispanic women, even though they get breast cancer less often. The cost of probing the genetic code in research studies continues to drop. This is driving many researchers to cover virtually all genes in efforts to determine which of the bits of DNA that vary from person to person are associated with increased risk for a particular disease. However, Ziv and Fejerman have taken an approach that is simpler and that they say works just as well when the risk for a disease is very different between different ethnic groups. Researchers call it an “admixed” population study. They report the first results from their study in the December, 2008 issue of Cancer Research. We’re all genetic mosaics, with some genes inherited from our mothers and other bits from our fathers. To make matters more complicated, the matching pairs of mom-and-pop chromosomes we possess swap bits of DNA before we make the sperm or egg cells. In sperm and egg, the DNA is halved — the 23 chromosomes are unpaired. Chromosome pairs reform when sperm and egg combine to give rise to the next generation. The recombination step amounts to an extra bit of gene shuffling to increase genetic variability. Individuals who self-identify as Hispanic most often combine at least two racial groups from among European, Native American and African populations. Hence, the population is said to be admixed. Because these groups did not mix in the new world until just a few hundred years ago, the genetic cards that get shuffled in each generation have not been shuffled often enough to make for a homogenous mix. Instead, the genetic mosaic pattern among individuals in this group is made up of bigger pieces that can be traced back to their continents of origin. For Ziv, Fejerman and others, this fact makes it potentially easier to solve genetic puzzles. The bits inherited from one group or the other tend to be large and their ethnic origins easier to identify. “You end being able to say this portion of this chromosome came from Europe, and this portion of this chromosome came from the Americas, this portion from Africa,” Ziv says. Genetic variations differ in how often they occur in different ethnic or racial populations, including genetic variations that contribute to disease risk. What the researchers learn about genetic risks in women and their descendants from Latin American and other Spanish cultures might also shed more light on breast cancer risks for all women. “It will give us insights that are particular to this population, because we are directly studying this population, but I think it will also give us some insights on other populations,” Ziv says. The UCSF researchers also plan to look for interactions between genes and environment. “For instance, we know that hormone replacement contributes to breast cancer risk. But does it increase the risk the same way in all populations? In our admixed population, does the environment have a greater impact on women with a certain kind of genetic ancestry?” So far, among Latinas in the Bay Area included in the study, the researchers have determined that European ancestry is associated with increased breast cancer risk. Additional work will help them to better sort out environmental and genetic reasons for this association.