Waterproof.
A mutation in the enzyme NQO1
NCI
breast cancer patients with a mutation makes breast cancer cells more difficult to treat and more likely to spread. in both copies of the NQO1 gene have a survival rate of 20% less than 5 years after treatment than do patients without mutation, according to a new study of more than 2,000 Finnish women. Those with the mutation were also four times less likely to respond to a common type of chemotherapy.
NQO1 encodes an enzyme that protects cells against oxidative stress, damage to the cell and its DNA caused by reactive by-products of metabolism. The NQO1 enzyme also helps stabilize p53, sometimes called protein "guardian angel" for his crucial role in the prevention of tumors. Because NQO1 protects the DNA of a cell and its anti-cancer proteins, mutations that compromise the NQO1 enzyme are pernicious. A mutation, called NQO1 * 2, increases the risk of cancer or relapse of cancer, particularly leukemia.
A group of researchers from the University of Helsinki in Finland thought NQO1 could also be a promising predictor of survival of women with breast cancer. The team followed up the cases of 1,005 women who visited the Helsinki University Hospital for treatment of breast cancer between 1997 and 04. They tested the women for NQO1 * 2 mutation and compared their survival rate an average of nearly 6 years of follow-up visits. Only 65% of women who carried two defective copies of the gene were alive 5 years after treatment, 85% against and 87% survival for women with one and two good copies, reports the team today in Nature Genetics . The mutation also increases the risk that cancer will spread. Moreover, the mutation seemed to make breast tumors resistant to a common form of chemotherapy, epirubicin. Women with two copies of NQO1 * 2 mutation only had a survival rate of 17% at 5 years after treatment, compared to a survival rate of 75% for women with at least one good copy of the gene. For radiotherapy or hormone therapy, the NQO1 * 2 mutation seemed to make no difference.
To confirm their findings, the researchers studied a second group of 1,162 women treated in two other Finnish hospitals. Again, they found reduced survival: Over 10 years, 46% of women with two copies of NQO1 * 2 survived, against 75% of women with at least one NQO1 normal gene. As in the previous group, the effect was more pronounced in patients who received chemotherapy rather than radiation - but most women in the second group received an older type of chemotherapy, so that researchers could not confirm the effect of NQO1 * 2 mutation on the now common epirubicin therapy.
However, "the results are quite dramatic," says Carl Blomqvist, a cancer clinician and author of the study. "The immediate thing to do," he adds, is to launch a new clinical trial designed not only to detect the association between NQO1 * and prognosis, but to really test the predictive power of NQO1 * 2 on cancer prognosis in women randomly assigned to epirubicin and other therapies. If the connection holds, it could give doctors another information to help them choose the right treatment for a patient.
"it is an important discovery," says David Ross, a toxicologist at the University of Colorado, Denver. He also emphasizes the need for a new clinical trial to confirm the link between NQO1 * 2 and prognosis, adding that the cause of the effect is uncertain. "Always be certain t crossed and i dotted," he said.
Related site
- More information about cancer within the National cancer Institute
0 Komentar