Researchers Find Ovarian Cancer Risk Related To Inherited Inflammation Genes

In a study conducted by researchers at Moffitt Cancer Center and colleagues from 11 other institutions in the Unites States and the United Kingdom, genes that are known to be involved in inflammation were found to be related to risk of ovarian cancer.

Their study appeared in a recent issue of Cancer Research, published by the American Association for Cancer Research.

Chronic inflammation is known to influence risk of several cancers, including ovarian cancer. The researchers identified 27 genes that are involved in inflammation and sought to determine whether inter-individual differences in these genes were related to risk of ovarian cancer. To do that they determined the frequency of 162 single-nucleotide polymorphisms (SNPs, pronounced “snips”) in DNA extracted from a blood sample provided by approximately 900 women with ovarian cancer (cases) and 1000 cancer-free women (controls). Whenever a SNP is observed it means that there are two forms (alleles) of the gene and the least common one is termed the “minor allele.” The frequency of 21 of the 162 SNPs differed between the cases and controls and was subsequently examined in a larger study that included 3,100 cases and 2,100 controls from five independent studies.

“When we examined the relationship between SNPs in inflammation-related genes and the risk of ovarian cancer, we found variants in five of the 27 genes were related to risk. What was interesting to us was that women who carried the minor alleles had lower ovarian cancer risk. Each SNP appeared to lower risk by about 10 percent,” explained study co-author Thomas A. Sellers, Ph.D., M.P.H., Moffitt executive vice president and director of the Moffitt Research Institute.

One of the genes encodes Interleuken 1 alpha (IL1A), a cytokine, or a small signaling protein molecule that is involved in numerous immune and inflammatory responses, said the authors. IL1A has been associated with many inflammatory response conditions and diseases. In this study, the researchers found that IL1A, and another gene, AloX5, “appear to harbor common inherited variants associated with modest differences in the risk of ovarian cancer.”

Scientists have pinpointed a rare gene variant that increases a woman’s risk of developing ovarian cancer six-fold. The discovery will lead to new diagnostic tests to identify the cancer earlier and provides better information to help doctors choose targeted anti-cancer drugs.

Ovarian cancer can develop without many clear symptoms and is the fifth most common cancer in women. In the UK, 6,500 cases are diagnosed every year and, of those, almost 4,000 end in death.

In the latest study, scientists found that, in around 60 cases of ovarian cancer every year in the UK, the women had faults in a gene called RAD51D. Anyone who inherits a faulty version of this gene, they calculated, therefore had a one in 11 chance of developing ovarian cancer, compared with one in 70 for the general population.

“At this level of risk, women may wish to consider having their ovaries removed after having children, to prevent ovarian cancer occurring,” said Professor Nazneen Rahman, head of the division of genetics and epidemiology at the Institute of Cancer Research and the Royal Marsden hospital, who led the research. “There is also real hope on the horizon that drugs specifically targeted to the gene will be available.”

“The importance of inflammation pathways in the development of many cancers prompted us to examine this association between SNPS in inflammation-related genes and risk for ovarian cancer,” explained Sellers. “If these results can be confirmed, it might provide insights into how risk may be reduced, through strategies to lower chronic inflammation.”

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