A close look at a tumor’s or patient’s genetics can provide important, potentially lifesaving clues to avoiding and treating cancer. So say scientists who outlined their research Tuesday in five presentations at the American Association for Cancer Research’s annual meeting, in Denver.”This is an interesting set of presentations,” John S. Witte, a professor in the Institute for Human Genetics at the University of California, San Francisco, said during a midday press conference. “All the studies have an impact on the potential to predict risk or recurrence or response to treatment,” he said. In the first study, researchers led by Dr. Charles Mullighan, an associate member at St. Jude Children’s Research Hospital, Memphis, discovered that children with acute lymphoblastic leukemia (ALL) who have mutations in the JAK tyrosine kinase gene generally have poor outcomes, including an increased risk of recurrence of their malignancy. The selecting suggests the gene is actually a potential diagnostic tool 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 condition. Although JAK mutations weren’t previously known to occur in children with ALL, they were discovered in ten percent of these individuals. The mutations were associated with a deletion of the genes IKZF1 and CDKN2A/B and poor end result. And, over four years, 71 percent of the children with JAK and IKZF1 alterations had a relapse of their disease, compared with only 23 percent for patients without these genetic alterations, the researchers found.
But there was good news, too. “Whenever we treated the malignancy cells with a JAK inhibitor, the cells died,” Mullighan stated. “This shows that these JAC mutations certainly are a new therapeutic target in this subtype of leukemia.” Another study on leukemia found that a set of genetic variants increases the risk for persistent lymphocytic leukemia (CLL). The findings of this study add more items to the puzzle and could lead to better prevention and prognosis of the condition, 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 each year, and 4,000 will die, so that it is among the rarer cancers, Slager said during the teleconference. However, “in case you have a member of family with chronic lymphocytic leukemia, your chances of getting the disease are eight occasions higher than that of the general population,” she noted. An earlier analysis recognized seven DNA sequencing aberrations called “single nucleotide polymorphisms” (SNPs) that may result in chronic lymphocytic leukemia. In the current study, experts confirmed these findings in a separate sample of sufferers. They found 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 is followed by a 39 percent improved risk with a separate SNP on the 6p25 gene.”Our results will hopefully understand the biology of the condition, which may help all of us predict the disease, and it could help all of us develop better remedies and prognostic markers,” Slager said. Outcomes of another study presented at the conference showed that genetic variants in what’s known as the microRNA digesting pathway may predict a woman’s risk for ovarian malignancy.”Ovarian cancer is the fifth leading reason behind cancer in ladies in the United States, and one of the major risk factors is a family group history of ovarian malignancy, indicating a genetic component contributes to ovarian cancer risk,” Dr. Xifeng Wu, a professor in the department of epidemiology at the University of Texas M. D. Anderson Cancer Middle in Houston, said through the teleconference. For the analysis, Wu’s and team evaluated 70 SNPs in eight microRNA pathway genes. They were extracted from 380 ovarian cancer cases, as well as from 146 healthy ladies.
The researchers found 16 SNPs which 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 had greater than a twofold increased risk, and the ones with eight or even more experienced over a fivefold increased 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 develop an ovarian cancer risk-prediction model, Wu said. In a fourth study, experts led by Dr. Gangning Liang, a co-employee professor of analysis in the division of urology at the University of Southern California, reported
selecting a DNA modification known as a “methylation design,” that may diagnosis bladder cancer and detect patients at risk for recurrence of the disease.
“Bladder cancer may be the fifth most common cancer in men and the sixth most common in ladies,” Liang said during the teleconference. “It 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 sufferers with invasive bladder tumors.
Comparing cancerous tissue with normal bladder tissue, they found 158 “hypermethylated” loci and 366 “hypomethylated” locations. In addition, they found 21 areas which were hypermethylated in the normal-appearing bladder tissue in individuals with bladder cancer.
These loci could 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 weighed against invasive tumors. This finding supports the idea that two types of bladder malignancy develop along different paths. Bladder cancer can certainly recur, Liang noted. “It requires regular and invasive monitoring. We believe these results are clinically useful and also have benefits for the patient, because we can identify these methylation changes in the patient’s urine,” he explained.
“So, we are able to use a noninvasive solution to monitor the patient and may also have the ability to display screen for bladder cancer in high-risk populations, like smokers,” this individual said. In a final report, experts led by Sunita Setlur, an instructor in pathology at Brigham and Women’s Hospital and Harvard Medical School, found simply no association between the gene variant UGT2B17 and the risk of prostate cancer. Although this gene have been linked to the risk for prostate cancer in two earlier research, this new research found no this kind of association. For the analysis, researchers looked at 269 males of whom 156 had prostate cancer. The researchers looked at the number of copies of the UGT2B7 gene and found 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 didn’t see any association between polymorphism of UGT2B17 and UGT2B28 with malignancy,” Setlur stated during Tuesday’s teleconference.