SNPwatch gives you the latest news about research linking various traits and conditions to individual genetic variations. These studies are exciting because they offer a glimpse into how genetics may affect our bodies and health; but in most cases, more work is needed before this research can provide information of value to individuals. For that reason it is important to remember that like all information we provide, the studies we describe in SNPwatch are for research and educational purposes only. SNPwatch is not intended to be a substitute for professional medical advice; you should always seek the advice of your physician or other appropriate healthcare professional with any questions you may have regarding diagnosis, cure, treatment or prevention of any disease or other medical condition.
New research suggests that a gene associated with breast cancer can influence a woman’s chances of surviving the disease, particularly if she receives a drug treatment commonly given after surgery, according to a study published online Friday in Nature Genetics.
Fagerholm et al studied the gene NQO1 in 1,005 breast cancer patients from Finland and found that a woman’s survival was associated with her genotype at a particular SNP in the gene – rs1800566. After 5 years, about 85% of patients with one or two copies of G at rs1800566 survived, whereas only 65% of those with two A versions (AA genotype) did. The researchers saw similar results were seen in a second set of 1,162 Finnish female breast cancer patients – 72% of GG and GA genotype patients survived after 10 years, while only 46% of AA genotype patients did.
These results could impact a large number of women – according to the study 4% of people of European descent and up to 20% of the Asian population have the AA genotype at rs1800566.
Epirubicin is part of a drug cocktail that is often given as a chemotherapy treatment after removal of a breast tumor. When Fagerholm et al studied a subset of patients who received the treatment, they found that those with the AA version of rs1800566 were much less likely to survive.
The survival rate for women with the GG or GA genotype at rs1800566 who received epirubicin-based chemotherapy was 75% after 5 years. But for those women receiving epirubicin who had the AA genotype at this SNP, the survival rate was only 17%. There was no statistical difference in this study in survival rate for women who received other types of treatment or no treatment at all, regardless of their genotype.
The A version of rs1800566 causes a change in the protein sequence of NQO1 that results in the protein being destroyed by cells. Having the AA genotype at rs1800566 leaves cells completely devoid of NQO1 protein. Laboratory tests found that cells with the AA genotype, as well as cells engineered to lack the NQO1 protein (mimicking the AA genotype), were not as efficiently killed by epirubicin as cells that do contain the protein. The study showed that the effectiveness of other types of cancer treatment, including radiation and other drugs, were not affected by rs1800566 genotype or the amount of NQO1 present.
Approximately 20% of breast cancer tumors have a mutated version of an important tumor suppressor protein called p53. When the researchers analyzed the original group of 1,005 patients according to whether or not their tumors had this mutation (p53 information wasn’t available for the second study group), the AA genotype at rs1800566 had an effect only in women whose tumors had mutated p53. Only 20% of these women survived 5 years, whereas 73% of women with the GG or GA genotype and mutated p53 survived. In women with normal p53 protein, rs1800566 did not affect survival.
Based on the clinical and experimental results in their report – and the fact that the NQO1 protein is known to interact with the p53 protein – the authors speculate that NQO1 and p53 not only work together to prevent cancer but are both needed for drugs like epirubicin to destroy cancer cells that do develop.
The researchers theorize that in cells with functional copies of both the p53 and NQO1 genes, epirubicin treatment causes cell death. In cells that are deficient in either one of these proteins the effects of epirubicin may be less pronounced, but the end result is still the desired cancer cell death. But in cells that lack functional copies of both p53 and NQO1, the researchers think that signaling pathways are disturbed in such a way that epirubicin treatment not only is ineffective at killing cancer cells, but it may even enhance cancer cell survival and/or promote progression and spread of the disease.
The authors say that although more studies will be needed to confirm their findings, “NQO1 genotype may provide a predictive factor for treatment, possibly in combination with p53 status, both for primary tumors and, crucially, in metastatic breast cancer, where response to chemotherapy is critical for the treatment outcome and life expectancy.”