Dr. Avraham Raz, Ph.D.
A study by Avraham Raz, Ph.D., professor of pathology and radiation oncology, and collaborators Vitaly Balan, Ph.D., research associate and Pratima Nangia-Makker, Ph.D., assistant professor of pathology in the School of Medicine and the Barbara Ann Karmanos Cancer Institute, was published in the Dec. 15, 2008, edition of Cancer Research, a scientific journal supported by the American Association for Cancer Research Inc. In addition, an image from the study – the graph of allelic variations in Asian and Caucasian women superimposed over an image of galectin-3 expression in cancer patients – was featured on the cover of the issue.
The study provides evidence that an allelic variation in the galectin-3 gene may influence a woman’s risk for developing breast cancer and partially explain why Caucasian women have a higher occurrence of breast cancer than Asian women.
Despite a tremendous amount of variations in cancer incidence and mortality between races, Dr. Raz’s study is the first to identify a genetic contributor for those differences. “It is well-established that Asian women have a lower propensity for breast cancer than Caucasian women,” he said. “Up until this point, it has largely been attributed to differences in lifestyle, diet and local environment. Our study shows for the first time that in addition to these factors, inheritable genes such as galectin-3 also contribute to differences in breast cancer between races. This opens a new vista of research in the understanding of the disease.”
The association between galectin-3 gene and breast cancer was first discovered by Dr. Raz’s lab 20 years ago. It is widely expressed in various tumor cells and is also linked to metastasis, the spread of cancer from the primary tumor to other parts of the body.
For this study, his laboratory initially set out to determine whether variations in the galectin-3 genome influence a woman’s likelihood to develop breast cancer. They performed a genotype analysis of cancer patients and cancer-free women, categorizing them based on an allelic variation that leads to the expression of the amino acids histidine (H) or proline (P). It was then that a correlation between the H allele and cancer in Asian and Caucasian women became apparent.
“The H allele is far less frequent in Asian women than it is in Caucasian women, and this difference is similar to the distribution of breast cancer in Asian and Caucasian women,” Dr. Raz said. “This highlights the role of this gene in breast cancer incidence and development.”
Numerous attempts have been made to identify potential breast cancer risk alleles and genetic signatures with limited results. Although mutations in the genes BRCA1 and BRCA2 were identified as genetic risk factors a decade ago, they account for only 5 percent of breast cancer cases.
Further studies that analyze larger groups of people and include more races need to be conducted to determine the extent to which galectin-3 influences a woman’s risk of developing breast cancer. Once researchers have more information, they may be able to develop drugs that target high risk genes and prevent the onset of cancer. A long-term goal for identifying high risk genes for cancer is genome screening, wherein patients who are found to have breast cancer-associated genes will be followed more closely or more frequently, so that signs of cancer can be detected as early as possible.
“Dr. Raz’s brilliant research is leading us closer to discovering the genetic risk factors for developing breast cancer,” said Dr. Gloria Heppner, associate vice president for Research at WSU. “His work at Wayne State and the Karmanos Cancer Institute is another example of the tremendous research we are doing to uncover the cause of this deadly disease, which will lead us to new treatments, ultimately giving hope to many.”