Ever since their known occurrence in women, scientists and medical professionals have tried to determine the cause of breast and ovarian cancer. Now it appears they have. An American study involving families with a medical history of breast and ovarian cancer has linked the high prevalence of these cancers with mutation of the BRAC1 gene, located on chromosome 17.
The BRAC1 gene usually encodes a specific sequence of amino acids that supress tumour growth - what might be considered an ‘anti-cancer’ protein. However, mutations present in the gene itself, which include 11-base pair deletions, 1-base insertions, stop codons and nonsense substitutions, cause a different protein to be transcribed. The resulting protein is either non-viable or dysfunctional, meaning that it cannot perform its intended purpose.
The BRAC1 gene is usually expressed in both breast and ovarian tissue. As a result, those who possess mutations of the BRCA1 gene lack functional tumour suppressor proteins in these areas, leaving them highly susceptible to unregulated growth of cells.
In addition to finding a potential cancer-associated gene, the study posed what is perhaps the single most puzzling oncological dilemma: If the mutant form of the BRAC1 gene is recessive, why is there such a strong pre-disposition to cancer within families - inherited as though it were a dominant trait? Results showed that whenever chromosome loss was observed in the tumours of subjects who carried the mutant allele, it was invariably the chromosome containing the ‘normal’ allele that was lost. In other words, the mutant gene was only expressed when the normal variant of the gene was lost or inactivated in some way.
Now that researchers have pin pointed the very gene in which breast and ovarian ‘cancer-causing’ mutations occur, there is significant hope that this knowledge may be applied to the treatment and diagnosis of these cancers. Current clinical treatment options for breast and ovarian cancer include surgery, chemotherapy and radiation therapy. Whilst these procedures are moderately successful, they are also frequently damaging, disfiguring and all too often futile. However, if knowledge regarding the purpose and location of the BRCA1 gene were to be combined with genetic testing technology, women may be able to better understand their genetic predisposition status to breast and ovarian cancer.
Original article: A strong candidate for the breast and ovarian cancer susceptibility gene BRCA1
Miki, Y., Swensen, J., Shattuck-Eidens, D et.al 1994, ‘A strong candidate for the breast and ovarian cancer susceptibility gene BRCA1’, Science, 266, 5182 pp. 66-71.