Scientists have found four new genes that may play a role in breast cancer -- a finding which could one day improve screening for the disease which strikes one in nine women.
But perhaps just as important is the method used by Cancer Research UK and an international group of scientists in mounting the large-scale hunt for these genetic culprits -- a genome-wide search that may revolutionize how researchers look for disease-causing genes in the future.
University of Cambridge scientist Dr. Douglas Easton and his colleagues looked at the genetic makeup of nearly 50,000 women to find these new genes. What they found was that women at a high risk of cancer consistently showed differences in the general neighborhood of these four genes -- suggesting that they play a role in breast cancer development.
The study is published in the current issue of the journal Nature.
"This is an outstanding discovery," says Dr. Harpal Kumar, Cancer Research UK's chief executive, in a press release on the study issued Sunday.
"These findings will open doors for cancer researchers across the globe to unearth even more genes linked to cancer, and ultimately this will benefit patients," Kumar said.
"What electrifies the scientific community about these discoveries is that they point towards novel pathways or mechanisms that may help us unlock the secrets of this deadly disease," said Dr. Francis Collins, director of the National Human Genome Research Institute.
Because a woman's genetic background clearly increases her risk of breast cancer, scientists are constantly searching for the genes that cause it.
The four new breast cancer genes are very common, with a high proportion of the population carrying at-risk genes. For example, Easton and his colleagues estimate that 14 percent of the female population in the United Kingdom carries one of these genes.
But the researchers say that the increases in risk associated with the newly identified genes are likely small compared to the risk associated with previously identified breast cancer genes BrCA1 and BrCA2, which increase a woman's lifetime risk of breast cancer to between 50 percent and 85 percent.
Since these genes confer such a small increase in breast cancer risk, they are not appropriate for genetic testing at this point.
"For most women it doesn't really change any particular advice or anything," Easton said. "People should not generate anxiety in tests for these genes."
In fact, these four genes may just be a drop in the bucket considering the vast number of genes that likely contribute in some way to a woman's risk of breast cancer.
"There is no single breast cancer gene just as there is no single diabetes gene or prostate cancer gene," notes Dr. Teri Manolio, director of population genetics at the National Human Genome Research Institute. "What we have is many genes of small effect that, working together and with specific -- and as yet largely unknown -- environmental exposures, cause a woman to develop breast cancer."
Still, as more breast cancer genes are found, a comprehensive test to search for a multiple low-risk genes could prove useful.
"Looking at many risky genes may be better able to predict one's chance of getting breast cancer than looking at any single index alone," comments Debu Tripathy, clinical professor of internal medicine at University of Texas Southwestern Medical Center.
If a woman were found to have multiple low-risk genes, her doctor might advise her to undergo early screening and prophylactic treatment for breast cancer. But since 75 percent of breast cancer's genetic risk remains unexplained, such tests are still largely speculative.
When scientists first began searching for disease-causing genes, they usually had to start out knowing where to look.
The approach used to find the four new genes departed from older methods in that it allowed scientists to "Google" the genome, zeroing in on genes that appeared most in women with breast cancer.
"Rather than fish for new genes one at a time with a rod and line, we have trawled the pool," notes author Professor Bruce Ponder, director of the Cancer Research UK's Cambridge Research Institute, in the press release.
"This is not only a more efficient approach, it gets round the bias of previous studies in which scientists only examined genes they already know something about."
By contrast, Easton and his colleagues did not have to begin with any preconceived notions of where to look. This allowed them to discover genes in areas of the genome not previously investigated.
Dr. Kenneth Offit, chief of clinical genetics at Memorial Sloan-Kettering Cancer Center, acknowledges the strengths of this approach, but also highlights the questions it brings with it.
"This study is a tour de force of enormous size addressing an important question in cancer genetics," he said. "Its major significance is in the new scientific questions it raises rather than the questions resolved."
Indeed, what do these genes do? How do they increase a woman's risk of breast cancer? Dr. Marisa Weiss, president and founder of Breastcancer.org, notes, "This technique is good at finding possible genetic leads -- but it doesn't tell you why or how or what the culprit might actually have done to cause the problem."
Dr. Anthony Elias, Medical Director of the Breast Cancer Program at the University of Colorado, noted that we need to interpret these data with caution.
"Until we can put together a model of breast cancer risk by manipulating these [genetic variations] and demonstrating causality," he said, "we will not understand whether the association if causality, chance, statistical fluke, or as an innocent adjacent or related bystander."