At least 10 percent of ovarian cancers are inherited, and many of these cases are in women with a mutant BRCA1 allele. The current study controlled for more outcome predictors than any of the previous studies and could not find a measurable difference in survival due to hereditary BRCA1 dysfunction.

"Our study could not validate previous conclusions that women with inherited ovarian cancer have a better overall prognosis than those who have sporadic or random ovarian cancer," said Richard Buller, M.D., Ph.D., the study's principal investigator. "It still might be the case that hereditary ovarian cancer offers some increased survival over other ovarian cancers but we can't prove it with this study. Apparent survival differences are probably due to other factors."

Buller said the findings have implications for giving patients more accurate prognostic information. "Based on what we've learned, I can no longer tell women that having inherited ovarian cancer makes their prognosis better," he said. "The studies that would have allowed me to give that prognosis didn't have the appropriate controls that our study does."

Previous studies had shown an average 80 percent survival advantage for women who had hereditary BRCA1 gene dysfunction. Buller said the recent investigation included enough cases to have detected that 80 percent rate if it indeed existed. "Our next step will be to try to analyze more ovarian cancer cases. An even larger number of cases will increase our ability to detect a smaller difference in survival, such as 30 percent, if it exists," he said.

The current study focused on 59 cases of ovarian cancer that showed BRCA1 dysfunction due to one of three causes --- inheriting a defective allele, mutation but was not inherited, or a loss of gene function in the cancer (also known as gene silencing) --- and 59 cases of ovarian cancer in women with normal BRCA1 genotype. No previous study had controlled for the non-inherited forms of BRCA1 dysfunction or for a mutated p53 gene. All cases had been diagnosed, treated, or both at the same American cancer center.

Instead of comparing the survival rates among the groups with the three different types of BRCA1 dysfunction, the study compared each BRCA1 group with a carefully matched control group that did not have any BRCA1 dysfunction. For example, the team compared women with the first type of BRCA1 dysfunction --hereditary -- to women who were alike in every other way, such as age at diagnosis and post-treatment condition, with the exception that genotype was normal. The two groups had virtually identical survival rates: 4.5 years and 4.6 years (for hereditary BRCA1 defect and normal genotype, respectively).

"We controlled for the common outcome predicators in ovarian cancer so that we were very careful to compare apples to apples instead of apples to oranges," Buller said. "You can't just take a general population of ovarian cancer patients to study their survival. You need to consider whether they have any BRCA1 dysfunction plus other variables that could explain differences between groups, such as age of diagnosis, disease stage and the amount of disease left after surgical treatment."

He noted that women with cancers in which gene silencing is present have more tumor left after surgery than women with a mutant BRCA1 allele, yet the difference in residual tumor apparently is unrelated to gene dysfunction.

"If differences in survival were caused by just a problem with the gene, then you would expect women with mutated and silenced BRCA1 genes to have the same amount of disease left after surgery. After all, in both cases, that gene doesn't work," Buller said. "However, since the amount of tumor remaining differs, some factor other than the gene may have an influence."

Buller said that care needs to be taken in interpreting studies, whether they support or reject possible causes and effects. "When you interpret a study that shows a link, such as between a genetic condition and an increased survival rate, you need to be sure you have controlled for all the important variables," he explained. "Likewise, when interpreting studies that indicate a link does not exist, as with our investigation, you must be sure that you studied enough cases not to have overlooked any differences."

Last January, Buller and colleagues showed that BRCA1 gene dysfunction in women with ovarian cancer is more common than previously thought and that it frequently occurs through ways other than inheritance. That study indicated that up to 25 percent of women with ovarian cancer have some type of BRCA1 dysfunction. The BRCA1 gene is a tumor suppressor gene; however, its exact function is not known.