An alteration in the gene that regulates the G-protein signaling pathway has been linked to a reduced risk for bladder cancer in a case-control study.
The single nucleotide polymorphism (SNP) rs10759 found on the RGS4 gene conferred a 0.77-fold reduced risk for nonmuscle-invasive bladder cancer (NMIBC).
Other alterations in the regulator of the G-protein signaling (RGS) pathway were linked to NMIBC recurrence and progression and to patient survival in muscle-invasive bladder cancer (MIBC).
"Our current findings have significant clinical implications in personalized medicine," Dr. Eugene Lee and his colleagues report in an early online edition of Cancer (March 25; doi:10.1002/cncr.27871).
"By identifying individuals at increased risk for bladder cancer, we have the ability to initiate comprehensive screening," wrote the authors from the University of Texas MD Anderson Cancer Center in Houston. In addition, the findings could lead to better treatment, with the potential to target patients who may require earlier systemic chemotherapy or treatment with novel targeted agents.
"Furthermore," Dr. Lee noted in a press statement, "we can identify patients who already have a diagnosis of bladder cancer that are at increased risk of worsening of disease or dying."
The ultimate goal, he adds, "is to find as many genetic alterations that confer risk and create a panel of markers that would aid in diagnosis, treatment, and follow-up."
The RGS pathway produces a heterogeneous group of proteins that are involved in cell signaling. Genetic alterations in the pathway have already been linked to several tumors, including breast, prostate, lung cancers, and squamous cell cancer of the head and neck.
The study population consisted of 1,606 individuals, 803 of whom had newly-diagnosed, histologically confirmed, untreated bladder cancer. Each of these individuals was matched, based on age, gender, and ethnicity, to a healthy individual without a history of cancer.
Cases and controls were demographically similar, with a mean age of about 64 years; 79% of participants in each group were men and all were white. Not surprisingly, a higher percentage of patients than of controls were current (23% vs. 8%) or former (50% vs. 47%) smokers.
A total of 85 SNPs in 17 RGS genes were assessed for their potential association with bladder cancer risk, recurrence and progression in nonmuscle-invasive disease, and survival in muscle-invasive.
Bladder cancer risk was associated with six SNPs, including rs10759, which had the only, and the strongest, association for a positive outcome. Individuals with two or more of the five unfavorable SNPs were twice as likely as those without the SNPs to have bladder cancer. The presence of all five unfavorable SNPs increased four-fold the risk for bladder cancer.
NMIBC affected just more than half (52%; n = 421) of the bladder cancer patients, with 11 SNPs linked to disease recurrence and 13 to disease progression to MIBC.
Of patients who presented with MIBC, 10 SNPs were found that either increased or decreased the risk of death. Of these, two SNPs, and rs234473 on the RGS5 gene in particular, conferred the greatest risk of a poor survival outcome. Indeed, patients who had rs234473 had a lower median overall survival of 13.3 months, compared with 81.9 months in those where the genetic variant was absent.
The study was funded by several grants from the National Cancer Institute and by the University of Texas MD Anderson Cancer Center Research Trust. The authors made no conflict of interest disclosures.
The study was funded by the National Cancer Institute and by the University of Texas MD Anderson Cancer Center Research Trust. The authors made no conflict of interest disclosures.