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A high school student from Albany, New York, has made a significant contribution toward understanding how mutations to a gene called BRCA-1 contributes to hereditary breast cancer.
Meaghan Figge, a sophomore at Albany Academy for Girls, published her results in the June issue of Cancer Epidemiology Biomarkers and Prevention, detailing the likely sites for BRCA-1 mutations leading to breast cancer. Figge is a student member of the American Association for Cancer Research, which publishes CEBP.
Figge pursued her research in memory of her grandmother, Helen Luciw, who died from breast cancer at age 64. Meaghan was in the fourth grade at the time, and in the years since, wondered whether screening methods other than the mammogram that detected her grandmother's tumor could diagnose cancer at an earlier stage. Her curiosity led her to the literature biomedical research where she learned about BRCA-1, which under normal circumstances, acts to suppress tumors.
"I was curious about BRCA-1 gene," Figge recalled. "On my own time, I read literature and did independent science research at my school to learn all I could about how this gene was related to breast cancer."
Figge learned that normally, the BRCA-1 protein acts to suppress breast and ovarian tumors in women.
But when the genetic code for BRCA-1 is errantly altered, the gene may lose its ability to suppress tumors.
"Some women inherit abnormal forms of BRCA-1 and are at an increased risk of developing breast or ovarian cancer," she said.
The abnormal forms of the gene result in a protein form of BRCA-1 that contains amino acid substitutions that differ from the normal gene. Changes in the amino acid composition of the BRCA-1 protein stem from alterations in the genetic sequence of nucleotides that make up the coding for the gene, which is part of each woman's unique DNA makeup.
Although only five to 10 percent of all breast cancer cases are linked to inherited genes, women with abnormal BRCA-1 genes have as much as almost 90 percent more risk of developing breast cancer during their lifetime. Half of all hereditary cases of breast cancer are associated with abnormal BRCA-1 genes.
The BRCA-1 gene is not unique to humans. The scientific literature already documents that the gene sequence for BRCA-1 remains similar across a number of mammalian species. Humans and dogs share about 96 percent of the same coding sequence within the gene, while humans and rodents such as mice and rats have less consistency in gene sequence--about 65 percent of the genetic coding is similar.
Figge considered whether the amino acids that were encoded by the conserved portion of the BRCA-1 gene found in the various species served as potential mutations sites leading to loss of function of the gene and increased risk for breast cancer for the person carrying the gene.
Under the guidance of her mentor, chemistry teacher, and manuscript co-author, Lynda Blankenship, Figge examined 246 different BRCA-1 sequence mutations found in humans considered at high risk for breast or ovarian cancer. The genetic information for those people was provided from many different clinical settings and compiled in the NIH Breast Cancer Information Database--a repository of genetic sequences for a multitude of genes found in breast cancer patients.
Figge's analysis of the NIH data revealed that among the known BRCA-1 mutations, sites within the genetic coding that were likely targets of mutation were the same sites conserved among humans, dogs, rats and mice. Furthermore, Figge documented that among the conserved amino acids that make up the BRCA-1 protein in the four species, the amino acids that were most likely to be mutated were those that are hydrophobic. Mutated BRCA-1 proteins that exchange hydrophobic amino acid residues for more water-loving types of amino acids may undergo structural changes that lead to loss of function. The mutations found in the abnormal BRCA-1 versions may lead to proteins that are bent out of shape and unable to perform as tumor suppressers.
"Perhaps these missense mutations disturb important features of the BRCA-1 protein and play a role in breast and ovarian cancer formation," Figge said.
In addition to her current publication, Figge entered her research last year at the 13th annual Greater Capital Region Science and Engineering Fair and Science Congress at Rensselaer Polytechnic Institute. Her science was deemed worthy of advancing to the Intel International Science and Engineering Fair in May 2004 in Cleveland, Ohio. At the Intel fair, Figge won a special first place prize from the Endocrine Society.
As a contribution to the pool of knowledge upon which researchers build additional understanding of biomedical science, Figge's discovery may help clinicians determine the level of risk for a woman who carries specific versions of mutated BRCA-1 gene.
Founded in 1907, the American Association for Cancer Research is a professional society of more than 22,000 laboratory, translational, and clinical scientists engaged in all areas of cancer research in the United States and in more than 60 other countries. AACR's mission is to accelerate the prevention and cure of cancer through research, education, communication, and advocacy. Its principal activities include the publication of five major peer-reviewed scientific journals: Cancer Research; Clinical Cancer Research; Molecular Cancer Therapeutics; Molecular Cancer Research; and Cancer Epidemiology, Biomarkers & Prevention. AACR's Annual Meetings attract more than 15,000 participants who share new and significant discoveries in the cancer field. Specialty meetings, held throughout the year, focus on the latest developments in all areas of cancer research.