A close look at a tumor’s or patient’s genetics can offer important, possibly lifesaving clues to stopping and treating cancer. Therefore say researchers who outlined their analysis Tuesday in five presentations at the American Association for Malignancy Research’s annual conference, in Denver.”This is an interesting set of presentations,” John S. Witte, a professor in the Institute for Individual Genetics at the University of California, SAN FRANCISCO BAY AREA, said during a midday press meeting. “All the studies impact on the potential to predict risk or recurrence or response to treatment,” he stated. In the first study, researchers led by Dr. Charles Mullighan, an associate member at St. Jude Children’s Study Hospital, Memphis, discovered that children with acute lymphoblastic leukemia (ALL) who’ve mutations in the JAK tyrosine kinase gene generally have got poor outcomes, including a higher risk of recurrence of their malignancy. The obtaining suggests the gene could be a potential diagnostic device and a fresh therapeutic target. Despite improvements in treatment, some children with Most will relapse, Mullighan told reporters. For the analysis, the Memphis team analyzed the genes of 221 children with the disease. Although JAK mutations weren’t previously recognized to occur in children with ALL, these were discovered in 10 percent of these patients. The mutations were associated with a deletion of the genes IKZF1 and CDKN2A/B and poor outcome. And, over four years, 71 percent of the children with JAK and IKZF1 alterations experienced a relapse of their disease, compared with just 23 percent for sufferers without these genetic alterations, the researchers found.
But there was very good news, too. “When we treated the malignancy cellular material with a JAK inhibitor, the cellular material died,” Mullighan stated. “This shows that these JAC mutations are a new therapeutic focus on in this subtype of leukemia.” Another research on leukemia discovered that a couple of genetic variants escalates the risk for persistent lymphocytic leukemia (CLL). The findings of this study add more parts to the puzzle and may lead to better prevention and prognosis of the disease, in accordance to lead researcher Susan Slager, associate professor of biostatistics at the Mayo Clinic in Rochester, Minn.
About 15,000 Americans will establish CLL every year, and 4,000 will die, so it is one of the rarer cancers, Slager said during the teleconference. However, “for those who have a family member with chronic lymphocytic leukemia, your likelihood of obtaining the disease are eight instances greater than that of the general population,” she noted. A youthful analysis discovered seven DNA sequencing aberrations called “one nucleotide polymorphisms” (SNPs) that may result in chronic lymphocytic leukemia. In today’s study, experts confirmed these results in a separate sample of sufferers. They discovered the strongest genetic association for the condition was for a SNP on the 11q24 gene, where in fact the risk was 50 percent higher. This was accompanied by a 39 percent increased risk with another SNP on the 6p25 gene.”Our findings will hopefully understand the biology of the condition, which may help all of us predict the disease, and it may help us develop better treatments and prognostic markers,” Slager said. Outcomes of another study presented at the meeting showed that genetic variants in what’s known as the microRNA processing pathway may predict a woman’s risk for ovarian cancer.”Ovarian cancer is the fifth leading reason behind cancer in women in the United States, and one of the major risk elements is a family history of ovarian cancer, indicating that a genetic component plays a part in ovarian cancer risk,” Dr. Xifeng Wu, a professor in the section of epidemiology at the University of Texas M. D. Anderson Cancer Center in Houston, said during the teleconference. For the study, Wu’s and team evaluated 70 SNPs in eight microRNA pathway genes. These were extracted from 380 ovarian malignancy cases, along with from 146 healthy women.
The researchers found 16 SNPs that were predictive of ovarian cancer risk. Individuals who carried five or fewer of these SNPs had been at low risk for ovarian malignancy. However, individuals with six and seven SNPs got greater than a twofold increased risk, and those with eight or more had over a fivefold improved risk. In addition, as the amount of these SNPs increases, so does resistance to treatment and poorer survival, Wu said.
This information, and also other genetic and lifestyle risk factors, could be used to build up an ovarian cancer risk-prediction model, Wu said. In a fourth study, researchers led by Dr. Gangning Liang, an associate professor of research in the section of urology at the University of Southern California, reported
locating a DNA modification known as a “methylation design,” that may diagnosis bladder cancer and identify patients at risk designed for recurrence of the condition.
“Bladder cancer is the fifth many common cancer in guys and the sixth many common in women,” Liang said during the teleconference. “It really is mainly within smokers.”DNA methylation is a process in which genes can be either silenced or activated in malignancy. For the study, researchers measured DNA methylation in 12 patients who did not have bladder cancer, 52 patients with non-invasive bladder tumors and 39 patients with invasive bladder tumors.
Comparing cancerous cells with normal bladder tissue, they found 158 “hypermethylated” loci and 366 “hypomethylated” locations. In addition, they found 21 areas that were hypermethylated in the normal-appearing bladder cells in sufferers with bladder cancer.
These loci may be markers for identifying people at risk for bladder cancer, the researchers said. In addition, the scientists found that noninvasive tumors had a definite pattern of hypomethylation compared with invasive tumors. This obtaining supports the theory that two types of bladder malignancy develop along different paths. Bladder cancer can easily recur, Liang noted. “It requires frequent and invasive monitoring. We think these results are clinically useful and have benefits for the patient, because we can identify these methylation changes in the patient’s urine,” he explained.
“So, we can use a noninvasive solution to monitor the patient and may also be able to display screen for bladder malignancy in high-risk populations, like smokers,” he said. In a final report, researchers led by Sunita Setlur, an instructor in pathology at Brigham and Women’s Hospital and Harvard Medical College, found simply no association between the gene variant UGT2B17 and the chance of prostate cancer. Although this gene have been linked to the risk for prostate cancer in two earlier studies, this new research found no this kind of association. For the analysis, researchers looked at 269 men of whom 156 got prostate cancer. The researchers looked at the number of copies of the UGT2B7 gene and discovered that although deletion patterns for UGT2B17 and UGT2B28 genes were between 3.4 percent and 19.9,
this did not increase the risk for prostate cancer.”We did not see any association between polymorphism of UGT2B17 and UGT2B28 with malignancy,” Setlur said during Tuesday’s teleconference.