Genetic variations in the micro-RNA (miRNA) processing pathway genes and miRNA binding sites could predict a woman's risk of developing ovarian cancer and her prospects for survival.
The study by researchers from The University of Texas M. D. Anderson Cancer Center was the first to examine the association of genetic variants related to miRNA with ovarian cancer risk, overall survival for ovarian cancer patients, and platinum-based chemotherapy response.
Advertisement"We found a gene dosage effect, the more unfavorable variations a woman has, the greater her ovarian cancer risk and the shorter her survival time," said senior author Xifeng Wu, M.D., Ph.D., professor in M. D. Anderson's Department of Epidemiology.
They found that median survival, for example, ranged from 151 months for women with fewest unfavorable variations to 24 months for those with the most.
It was also found that many of the variations indicated likely response to platinum-based chemotherapy.
"Our findings have the potential clinical application of indicating a patient's prognosis and showing who will respond to different therapies by analyzing a single blood sample. We also will incorporate this genetic information with epidemiological information to build a comprehensive model to predict susceptibility to ovarian cancer," said Wu.
Researchers focused on the miRNA-processing pathway because it is crucial to production of miRNAs, the small molecules that regulate between one third and half of all genes.
Also, they chose the binding sites on host genes where miRNAs exert their effects on gene expression.
The study examined genetic information from 417 cancer patients and 417 healthy controls.
For the study, they analyzed 219 potential functional single nucleotide polymorphisms (SNPs), variations of a single DNA building block in a gene, in eight genes that process miRNA and at the miRNA binding sites of 129 cancer-relevant genes.
And it was found that 12 SNPs were significantly linked with ovarian cancer risk.
Also, the risk of developing ovarian cancer was 4.5 times more in women with five or fewer unfavorable genotypes as compared to those with eight or more of these unfavorable genotypes.
Women with six to eight unfavorable SNPs were at twice the risk.
The team also found that 21 SNPs were significantly associated with overall survival.
The findings of the study were presented at the 100th annual meeting of the American Association for Cancer Research.
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