The Role of Genetics in Diagnosis and Treatment of Prostate Cancer
Two major problems in the diagnosis and treatment of prostate cancer are not knowing: 1. who is at risk for the disease and 2. who is at risk for aggressive forms of the disease.
Answers to both of these questions would do a great deal to make testing, biopsy, and treatment more effective for those who need it and less necessary for those who might not.
Focusing on the Problems
Dr. Catalona and his collaborators are focusing their genetic research on two concerns – looking for the genetic markers related to prostate cancer risk and those related to aggressive prostate cancer.
This article prepared for Quest readers reports on their recent findings. Your donations to the Urological Research Foundation support this important genetic research, and we will continue to keep you informed of the progress.
Prostate cancer (CaP) is the most common non-skin cancer among men – with an estimated 192,000 new cases diagnosed in 2009. Although most men seem to have a form of the cancer that tends to grow and spread slowly, aggressive prostate cancer is currently the second leading cause of cancer death in men in the United States.
ALLELE: one of the altered forms of any segment of a chromosome.
Researchers look at specific DNA codes of known genes and at variations within these genes called alleles.
Most people have seen the very long and involved list of alphabet letters that represent a genetic code. In one area, a part of a code might be CCATT but in a substantial number of men with prostate cancer, that code is CAATT.
The place where the changed code is spotted (in this example, it is the second letter; C to A) is called an allelic or allele variation.
While the common use of PSA as a screening tool has contributed to a 40% reduction in age-adjusted, CaP specific mortality in the US, genetic biomarkers could assist in prostate cancer assessment and in predicting life-threatening disease.
That knowledge would help with treatment decisions – allowing some men with potentially slow growing cancers the option to consider different treatment interventions from those with potentially aggressive cancers. With present information, that educated option is not possible.
Although abundant evidence now demonstrates that specific alleles (see box below) significantly contribute to prostate cancer risk, reports concerning the association of the same genetic risk alleles with prostate cancer aggressiveness are subjects of debate.
Identifying Biomarkers for Aggressiveness
The important task is to identify and determine which risk alleles predispose to the development of prostate cancer and which ones may also predict aggressive tumor characteristics.
Recently, Dr. Catalona’s research group participated in a large, multicenter genome-wide association study which identified four prostate cancer risk alleles [located along chromosomes 3q21.3 (SNP rs10934853), 8q24 (SNPs rs16902094 and rs445114), and 19q13 (SNP rs8102476)]. In addition, five others were identified in previous studies.
This present study examined the relationship of these risk alleles with pathology features of prostate cancer and specifically their association with prostate cancer aggressiveness.
An intriguing finding of this study was the strong association of disease aggressiveness with the SNP rs16902094 risk allele on chromosome 8q24.
In the study population (Catalona’s surgical patients), the frequency of this prostate cancer risk allele correlated positively with increasing biopsy Gleason grade, increasing surgical specimen Gleason grade, and advanced stage disease. In addition, this risk allele is over-represented in patients with aggressive disease and under-represented in patients with possibly “insignificant” (indolent) disease.
Also interesting, the results of this study suggested that men who are carriers of the SNP rs10896450 on chromosome 11q13 and/or the SNP rs2736098 on chromosome 5p15 have a significantly higher frequency of possible “insignificant” disease.
This study examined men of western European background. Additional studies are needed to examine the prevalence and association of these prostate cancer risk alleles among different ethnic groups. African-American and Hispanic men in the US are encouraged to participate in future studies.
Also, all patients in the study underwent radical prostatectomy. These prostate cancer risk alleles should be examined in patients with more advanced disease undergoing primary radiation and/or hormonal therapy.
The findings in this study are important and should direct and encourage future studies aimed at confirming these associations.
As genetic testing becomes more common, information regarding prostate cancer risk and potential aggressiveness will influence diagnostic evaluation and treatment decisions.
Possibly, these risk alleles may be incorporated as a routine part of prostate cancer screening.
PSA Test Reduces Prostate Cancer Deaths By 40%
from *Zero, the Project to End Prostate Cancer (excerpt reprinted)
“The American Cancer Society is a ‘false prophet’ when it comes to telling the truth about the effectiveness of the PSA test,” said ZERO’s CEO Skip Lockwood.
“Dr. Otis Brawley disregards scientific data about the value of the PSA test in saving lives. In fact, his views at a recent medical conference were vigorously challenged by physicians and researchers in attendance.
“Dr. Brawley seems more concerned about sex than saving lives. He’s obsessed with the side effects of treatment rather than a solution for saving lives. He wants you to trust him instead of the 30,000 urologists in the U.S. and gamble you’re not among the thousands of men who die each year with aggressive prostate cancer tumors,” said Lockwood.
Lockwood acknowledges that the PSA test, like the mammogram, is not perfect.
“No one disputes that the PSA test cannot distinguish slow-growing tumors from rapidly growing ones, yet no one disputes that the PSA test is still the best tool available for early diagnosis and prompt treatment for prostate cancer.
“The long-term solution is to discover a new biomarker for prostate cancer – without false positives or negatives and one that determines who has a life-threatening disease and who doesn’t….”
One of the nation’s leading experts on prostate cancer, Dr. William J. Catalona of Northwestern University, commented, “Although the PSA test is not perfect, it is effective in identifying men at high risk for prostate cancer and for detecting it early.”
The PSA test, the most prevalent method in use today for prostate cancer, has saved thousands of lives. The PSA test and advances in treatment have led to a 40 percent reduction in prostate cancer deaths since the mid-1990s, according to the National Cancer Institute. Because of the PSA test, 90 percent of all prostate cancers are now discovered before they spread outside the gland, according to the American Cancer Society’s own data.
Dr. Patrick C. Walsh, distinguished professor of urology at Johns Hopkins University noted, “Because prostate cancer produces no symptoms until it’s too far advanced to cure, as appropriate, men should have a PSA test and examination.”
* Zero’s mission is not only to reduce prostate cancer or alleviate the pain from the disease but to end it.