Roxanne Nelson

November 19, 2008

November 19, 2008 — Black men and those with a family history are at a 2- to 7-fold increased risk for prostate cancer. Although assessing risk has been difficult in these populations, researchers now report that 5 genetic single-nucleotide polymorphisms (SNPs) might be useful in determining prostate cancer risk in men who are already at higher risk for the disease.

Compared with white men, black men tend to carry more of the genetic risk markers, according to the data that were presented at the Seventh Annual American Association for Cancer Research International Conference on Frontiers in Cancer Prevention Research, held in Washington, DC. There was also a trend toward earlier development of prostate cancer in black men who carry more of these risk markers.

"Assessing the risk for prostate cancer through genetic testing is not available, as it is for breast cancer, and efforts toward preventing deaths from prostate cancer in these men have been focused on early detection," said lead author Veda N. Giri, MD, director of the Prostate Cancer Risk Assessment Program at Fox Chase Cancer Center, in Philadelphia, Pennsylvania.

However, this process often results in men who are deemed to be at higher risk, undergoing unnecessary biopsies, Dr. Giri pointed out during a press briefing. "The question is, how can we accurately predict the risk of prostate cancer in high-risk men in order to make personalized recommendations for screening and diagnoses?"

The More Markers, the Higher the Risk

In recent years, several genetic markers have been reported to be associated with prostate cancer. Five SNPs located at chromosomal loci 8q and 17q (rs1859962, rs6983267, rs4430796, rs1447295, and rs16901979) were found to have a cumulative increased association with prostate cancer in multiple studies. The more of these markers that men carry, the higher the risk for prostate cancer, explained Dr. Giri.

"The goal now is to determine the clinical use of these genetic markers in prospective populations, especially among men at high risk," she said.

The Prostate Cancer Risk Assessment Program is a prospective screening program for high-risk men that includes more than 700 participants, 60% of whom are black. The objective of the current study was to characterize the distribution of these 8q/17q risk markers, and to assess the time to prostate cancer based on the markers.

Men between the ages of 35 and 69 years were considered high risk if they had 1 first-degree relative with prostate cancer or 2 second-degree relatives with prostate cancer on the same side of the family. In addition, any black male, regardless of family history, and men with BRCA1/2 mutations were considered high risk.

Criteria for undergoing a biopsy included levels of prostate-specific antigen (PSA) higher than 2.0 ng/mL, PSA levels from 1.5 to 2.0 ng/mL with free PSA less than 25%, any abnormality observed on digital rectal examination, or PSA velocity of 0.75 ng/mL per year.

Genotyping was performed and standard statistical methods were used to determine allele and genotype distributions by race. Cox models used the number of high-risk SNPs to determine time to prostate cancer diagnosis.

Genotypes were determined for all 5 SNPs in 633 of the participants, and average follow-up time was 3 to 4 years. The researchers observed a statistically significant difference in the baseline distribution of risk alleles and risk genotypes of these 5 SNPs within the racial groups. Among white participants, the age-adjusted baseline PSA levels differed significantly among high-risk men. Participants carrying the risk genotype at rs4430796 had higher baseline PSA levels than those without the risk genotype at this SNP.

Markers More Informative in Black Men

Black men were more likely to carry 2 or 3 and 4 or 5 risk-associatedSNPs than high-risk white men. Among white high-risk men, Dr. Giri pointed out, they did not observe a trend toward time to diagnosis by increasing numbers of genetic markers. However, it was more informative for black men.

Among the 210 black participants who had at least 1 follow-up visit, there was a trend among those with 4 or 5 risk SNPs for earlier time to prostate cancer diagnosis, compared with men with 0 or 1 risk SNP. They also noted that the hazard ratios for prostate cancer risk increased substantially in black men with 4 or 5 SNPs, compared with those with 2 or 3 SNPs (4.28 vs 1.84), although it did not reach statistical significance.

The specific genetic markers studied here might be more informative in black men for predicting time to diagnosis of prostate cancer, explained Dr. Giri. "There is a need to study genetic markers that are associated with prostate cancer in prospective studies to understand their true value in the clinical setting, especially for high risk men."

"The 5 genetic markers that they identified were significant in the population that they evaluated, and that is an important step in the ultimate goal to genetically stratify men by risk," meeting chair Steven M. Dubinett, MD, told Medscape Oncology. "More work needs to be done to determine how useful these risk markers will be for prostate cancer diagnosis."

American Association for Cancer Research's Seventh Annual International Conference on Frontiers in Cancer Prevention Research: Abstract B54. Presented November 17, 2008.


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