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Brian K Suarez

Publications and source records attributed to Brian K Suarez.

At least 19 recordsLinked to original sources
PubMed2007

Prostate specific antigen density correlates with features of prostate cancer aggressiveness.

PURPOSE: An increased prostate specific antigen density (serum prostate specific antigen divided by prostate volume) is an established parameter to help determine the need to perform prostate biopsies. A man with a high prostate specific antigen and a normal size prostate gland is more likely to have cancer than a man with the same prostate specific antigen and a large gland. Prostate specific antigen in relation to prostate size should also reflect the volume of cancer in the gland. One group defined clinically unimportant prostate cancer as tumor volume less than 0.5 cc, organ confined disease and Gleason less than 7. Another group noted that at the time of biopsy, a prostate specific antigen density less than 0.15 ng/ml/cc combined with low risk clinical tumor features predicted insignificant cancer. There are limited published validating data on the association of prostate specific antigen density with the criteria for prostate cancer aggressiveness. We tested the association of prostate specific antigen density with features of tumor aggressiveness in a screened and in a nonscreened cohort of patients with clinically localized prostate cancer treated with radical prostatectomy. MATERIALS AND METHODS: The screened patient cohort included 1,280 patients with screen detected prostate cancer treated from 1990 to 2002 at Washington University, and the nonscreened cohort included 382 patients treated from 2003 to 2004 at Northwestern University. We recorded the clinical and pathological tumor parameters in a prospective database. Parameters evaluated were pathological tumor stage, Gleason sum, tumor volume, biochemical progression and the previously mentioned 2 criteria for clinically unimportant cancers. We grouped patients into 4 prostate specific antigen density categories of less than 0.1, 0.1 to 0.14, 0.15 to 0.19 and greater than 0.19 ng/ml/cc. RESULTS: There was a significant trend for worsening clinicopathological prognostic features as prostate specific antigen density increased. There were 357 (82%), 283 (75%), 171 (75%) and 192 (55%) men with organ confined disease with clear surgical margins if prostate specific antigen density was less than 0.1, 0.1 to 0.14, 0.15 to 0.19 and greater than 0.19 ng/ml/cc, respectively (p <0.001). There were 86 (20%), 102 (27%), 64 (28%) and 157 (45%) men with a Gleason sum greater than 7 when grouped into each increasing PSA density category, respectively (p <0.001). There were 91 (21%), 91 (25%), 74 (33%) and 157 (46%) men with a total cancer volume greater than 0.5 cc when grouped into each increasing PSA density category, respectively (p <0.001). Prostate specific antigen velocity was greater than 2 ng/ml per year in 11%, 30%, 27% and 46% of men if prostate specific antigen density was less than 0.1, 0.1 to 0.14, 0.15 to 0.19 and greater than 0.19 ng/ml/cc, respectively (p <0.001). CONCLUSIONS: Prostate specific antigen density measurements are useful in helping to determine the aggressiveness of clinically localized prostate cancer, and can be used as an adjunct in predicting insignificant cancer and outcomes after local therapy.

Aged↗
PubMed2006

Pooled genome linkage scan of aggressive prostate cancer: results from the International Consortium for Prostate Cancer Genetics.

While it is widely appreciated that prostate cancers vary substantially in their propensity to progress to a life-threatening stage, the molecular events responsible for this progression have not been identified. Understanding these molecular mechanisms could provide important prognostic information relevant to more effective clinical management of this heterogeneous cancer. Hence, through genetic linkage analyses, we examined the hypothesis that the tendency to develop aggressive prostate cancer may have an important genetic component. Starting with 1,233 familial prostate cancer families with genome scan data available from the International Consortium for Prostate Cancer Genetics, we selected those that had at least three members with the phenotype of clinically aggressive prostate cancer, as defined by either high tumor grade and/or stage, resulting in 166 pedigrees (13%). Genome-wide linkage data were then pooled to perform a combined linkage analysis for these families. Linkage signals reaching a suggestive level of significance were found on chromosomes 6p22.3 (LOD = 3.0), 11q14.1-14.3 (LOD = 2.4), and 20p11.21-q11.21 (LOD = 2.5). For chromosome 11, stronger evidence of linkage (LOD = 3.3) was observed among pedigrees with an average at diagnosis of 65 years or younger. Other chromosomes that showed evidence for heterogeneity in linkage across strata were chromosome 7, with the strongest linkage signal among pedigrees without male-to-male disease transmission (7q21.11, LOD = 4.1), and chromosome 21, with the strongest linkage signal among pedigrees that had African American ancestry (21q22.13-22.3; LOD = 3.2). Our findings suggest several regions that may contain genes which, when mutated, predispose men to develop a more aggressive prostate cancer phenotype. This provides a basis for attempts to identify these genes, with potential clinical utility for men with aggressive prostate cancer and their relatives.

Black or African American↗
PubMed2006

Variants in the HEPSIN gene are associated with prostate cancer in men of European origin.

There is considerable evidence that genetic factors are involved in prostate cancer susceptibility. We have studied the association of 11 single nucleotide polymorphisms (SNPs) in the HEPSIN gene (HPN) with prostate cancer in men of European ancestry. HPN is a likely candidate in prostate cancer susceptibility, as it encodes a transmembrane cell surface serum protease, which is overexpressed in prostate cancer; HPN is also located on 19q11-q13.2, where linkage is found with prostate cancer susceptibility. In this case-control association study (590 men with histologically verified prostate cancer and 576 unrelated controls, all of European descent), we find significant allele frequency differences between cases and controls at five SNPs that are located contiguously within the gene. A major 11-locus haplotype is significantly associated, which provides further support that HPN is a potentially important candidate gene involved in prostate cancer susceptibility. Association of one of the SNPs with Gleason score is also suggestive of a plausible role of HPN in tumor aggressiveness.

Case-Control Studies↗
PubMed2006

A common variant associated with prostate cancer in European and African populations.

With the increasing incidence of prostate cancer, identifying common genetic variants that confer risk of the disease is important. Here we report such a variant on chromosome 8q24, a region initially identified through a study of Icelandic families. Allele -8 of the microsatellite DG8S737 was associated with prostate cancer in three case-control series of European ancestry from Iceland, Sweden and the US. The estimated odds ratio (OR) of the allele is 1.62 (P = 2.7 x 10(-11)). About 19% of affected men and 13% of the general population carry at least one copy, yielding a population attributable risk (PAR) of approximately 8%. The association was also replicated in an African American case-control group with a similar OR, in which 41% of affected individuals and 30% of the population are carriers. This leads to a greater estimated PAR (16%) that may contribute to higher incidence of prostate cancer in African American men than in men of European ancestry.

Alleles↗
PubMed2006

Baseline prostate-specific antigen compared with median prostate-specific antigen for age group as predictor of prostate cancer risk in men younger than 60 years old.

OBJECTIVES: Limited data are available concerning the extent to which the initial prostate-specific antigen (PSA) measurement in men younger than age 60 predicts for the risk of prostate cancer (CaP) and how this compares to other known risk factors. METHODS: From 1991 to 2001, 13,943 men younger than 60 years old participated in a CaP screening study. Men aged 40 to 49 years were eligible for the study if they had a positive family history or African-American heritage, and men older than 50 years were screened without respect to risk factors. The CaP detection rate, PSA velocity, pathologic features, and treatment outcomes were evaluated as a function of the baseline PSA level. RESULTS: The median PSA level was 0.7 ng/mL for men aged 40 to 49 years and 0.9 ng/mL for men aged 50 to 59. A baseline PSA level between the median and 2.5 ng/mL was associated with a 14.6-fold and 7.6-fold increased risk of CaP in men aged 40 to 49 and 50 to 59 years, respectively. A greater baseline PSA value was also associated with a significantly greater PSA velocity, more aggressive tumor features, a greater biochemical progression rate, and a trend toward a greater cancer-specific mortality rate. CONCLUSIONS: In men younger than 60, a baseline PSA value between the age-specific median and 2.5 ng/mL was a significant predictor of later CaP and was associated with a significantly greater PSA velocity. A young man's baseline PSA value was a stronger predictor of CaP than family history, race, or suspicious digital rectal examination findings. A greater baseline PSA level was associated with significantly more adverse pathologic features and biochemical progression.

Adult↗
PubMed2006

Genomewide linkage scan of 409 European-ancestry and African American families with schizophrenia: suggestive evidence of linkage at 8p23.3-p21.2 and 11p13.1-q14.1 in the combined sample.

We report the clinical characteristics of a schizophrenia sample of 409 pedigrees--263 of European ancestry (EA) and 146 of African American ancestry (AA)--together with the results of a genome scan (with a simple tandem repeat polymorphism interval of 9 cM) and follow-up fine mapping. A family was required to have a proband with schizophrenia (SZ) and one or more siblings of the proband with SZ or schizoaffective disorder. Linkage analyses included 403 independent full-sibling affected sibling pairs (ASPs) (279 EA and 124 AA) and 100 all-possible half-sibling ASPs (15 EA and 85 AA). Nonparametric multipoint linkage analysis of all families detected two regions with suggestive evidence of linkage at 8p23.3-q12 and 11p11.2-q22.3 (empirical Z likelihood-ratio score [Z(lr)] threshold >/=2.65) and, in exploratory analyses, two other regions at 4p16.1-p15.32 in AA families and at 5p14.3-q11.2 in EA families. The most significant linkage peak was in chromosome 8p; its signal was mainly driven by the EA families. Z(lr) scores >2.0 in 8p were observed from 30.7 cM to 61.7 cM (Center for Inherited Disease Research map locations). The maximum evidence in the full sample was a multipoint Z(lr) of 3.25 (equivalent Kong-Cox LOD of 2.30) near D8S1771 (at 52 cM); there appeared to be two peaks, both telomeric to neuregulin 1 (NRG1). There is a paracentric inversion common in EA individuals within this region, the effect of which on the linkage evidence remains unknown in this and in other previously analyzed samples. Fine mapping of 8p did not significantly alter the significance or length of the peak. We also performed fine mapping of 4p16.3-p15.2, 5p15.2-q13.3, 10p15.3-p14, 10q25.3-q26.3, and 11p13-q23.3. The highest increase in Z(lr) scores was observed for 5p14.1-q12.1, where the maximum Z(lr) increased from 2.77 initially to 3.80 after fine mapping in the EA families.

Adolescent↗
PubMed2006

Association of hereditary prostate cancer gene polymorphic variants with sporadic aggressive prostate carcinoma.

BACKGROUND: ELAC2, MSR1, and RNASEL are candidate genes for hereditary prostate carcinoma (HPC). While, studies have demonstrated that single nucleotide polymorphisms (SNPs) in these genes are associated with sporadic disease as well as HPC, these results are often not replicated in follow-up studies. Given that the majority of patients studied had localized disease and up to 50% of localized prostate cancer is clinically insignificant, the inability to replicate the initial findings may reflect that some subjects had indolent tumors. Herein, we examine patients with metastatic disease to determine if an association exists between HPC SNPs and unambiguously significant prostate cancer. METHODS: We examined polymorphisms within ELAC2 (S217L, A541T, E622V), MSR1 (P275A, R293X, aIVS5-59c), and RNASEL (E265X, R462Q, D541E) in 150 European-Americans with metastatic prostate cancer and 170 prostate cancer-free controls using pyrosequencing assays. RESULTS: Only ELAC2 217L (37% cases vs. 29% controls (P=0.034)) and RNASEL 541E (61% cases vs. 53% controls (P=0.045)) were over-represented. Analysis of genotypes revealed that presence of the leucine ELAC2 allele (OR 1.54: 95% CI=0.99-2.41, SS vs. SL, LL) and homozygosity for the glutamic acid RNASEL allele (OR 1.68: 95% CI=1.04-2.70, EE vs. DE, DD) were associated with increased risk. Patients with both genotypes were of particularly high-risk (OR 2.66: 95% CI=1.36-5.19). CONCLUSIONS: These results suggest that, in a European-American population, ELAC2 217L and RNASEL 541E are associated with metastatic sporadic disease. ELAC2 and RNASEL SNP analysis may prove useful in determining which patients are at risk for developing clinically significant prostate carcinoma.

Base Sequence↗
PubMed2005

Microsatellites versus single-nucleotide polymorphisms in linkage analysis for quantitative and qualitative measures.

BACKGROUND: Genetic maps based on single-nucleotide polymorphisms (SNP) are increasingly being used as an alternative to microsatellite maps. This study compares linkage results for both types of maps for a neurophysiology phenotype and for an alcohol dependence phenotype. Our analysis used two SNP maps on the Illumina and Affymetrix platforms. We also considered the effect of high linkage disequilibrium (LD) in regions near the linkage peaks by analysing a "sparse" SNP map obtained by dropping some markers in high LD with other markers in those regions. RESULTS: The neurophysiology phenotype at the main linkage peak near 130 MB gave LOD scores of 2.76, 2.53, 3.22, and 2.68 for the microsatellite, Affymetrix, Illumina, and Illumina-sparse maps, respectively. The alcohol dependence phenotype at the main linkage peak near 101 MB gave LOD scores of 3.09, 3.69, 4.08, and 4.11 for the microsatellite, Affymetrix, Illumina, and Illumina-sparse maps, respectively. CONCLUSION: The linkage results were stronger overall for SNPs than for microsatellites for both phenotypes. However, LOD scores may be artificially elevated in regions of high LD. Our analysis indicates that appropriately thinning a SNP map in regions of high LD should give more accurate LOD scores. These results suggest that SNPs can be an efficient substitute for microsatellites for linkage analysis of both quantitative and qualitative phenotypes.

Alcoholism↗
PubMed2005

An analysis of identical single-nucleotide polymorphisms genotyped by two different platforms.

The overlap of 94 single-nucleotide polymorphisms (SNP) among the 4,720 and 11,120 SNPs contained in the linkage panels of Illumina and Affymetrix, respectively, allows an assessment of the discrepancy rate produced by these two platforms. Although the no-call rate for the Affymetrix platform is approximately 8.6 times greater than for the Illumina platform, when both platforms make a genotypic call, the agreement is an impressive 99.85%. To determine if disputed genotypes can be resolved without sequencing, we studied recombination in the region of the discrepancy for the most discrepant SNP rs958883 (typed by Illumina) and tsc02060848 (typed by Affymetrix). We find that the number of inferred recombinants is substantially higher for the Affymetrix genotypes compared to the Illumina genotypes. We illustrate this with pedigree 10043, in which 3 of 7 versus 0 of 7 offspring must be double recombinants using the genotypes from the Affymetrix and the Illumina platforms, respectively. Of the 36 SNPs with one or more discrepancies, we identified a subset that appears to cluster in families. Some of this clustering may be due to the presence of a second segregating SNP that obliterates a XbaI site (the restriction enzyme used in the Affymetrix platform), resulting in a fragment too long (>1,000 bp) to be amplified.

Female↗
PubMed2005

Multipoint identity-by-descent computations for single-point polymorphism and microsatellite maps.

We used the LOKI software to generate multipoint identity-by-descent matrices for a microsatellite map (with 31 markers) and two single-nucleotide polymorphism (SNP) maps to examine information content across chromosome 7 in the Collaborative Study on the Genetics of Alcoholism dataset. Despite the lower information provided by a single SNP, SNP maps overall had higher and more uniform information content across the chromosome. The Affymetrix map (578 SNPs) and the Illumina map (271 SNPs) provided almost identical information. However, increased information has a computational cost: SNP maps require 100 times as many iterations as microsatellites to produce stable estimates.

Chromosome Mapping↗
PubMed2005

The efficacy of short tandem repeat polymorphisms versus single-nucleotide polymorphisms for resolving population structure.

Accurately resolving population structure in a sample is important for both linkage and association studies. In this study we investigated the power of single-nucleotide polymorphisms (SNPs) in detecting population structure in a sample of 286 unrelated individuals. We varied the number of SNPs to determine how many are required to approach the degree of resolution obtained with the Collaborative Study on the Genetics of Alcoholism (COGA) short tandem repeat polymorphisms (STRPs). In addition, we selected SNPs with varying minor allele frequencies (MAFs) to determine whether low or high frequency SNPs are more efficient in resolving population structure. We conclude that a set of at least 100 evenly spaced SNPs with MAFs of 40-50% is required to resolve population structure in this dataset. If SNPs with lower MAFs are used, then more than 250 SNPs may be required to obtain reliable results.

Alcoholism↗
PubMed2005

Genotyping errors, pedigree errors, and missing data.

Our group studied the effects of genotyping errors, pedigree errors, and missing data on a wide range of techniques, with a focus on the role of single-nucleotide polymorphisms (SNPs). Half of our group used simulated data, and half of our group used data from the Collaborative Study on the Genetics of Alcoholism (COGA). The simulated data had no missing genotypes and no genotyping errors, so our group, as a whole, removed data and introduced artificial errors to study the robustness of various techniques. Our teams showed that genotyping errors are less detectable and may have a greater impact on SNPs than on microsatellites, but recently developed methods that account for genotyping errors help reduce false positives, and the assumptions of these methods appear to be supported by observations from repeated genotyping. The ability to detect linkage disequilibrium (LD) was also substantially reduced by missing data; this in turn could affect tagging SNPs chosen to generate haplotypes. In the COGA sample, genotyping measurements were repeated in three ways. First, full-genome screens were performed on three sets of markers: 328 microsatellites, 11,560 SNPs from the Affymetrix GeneChip Mapping 10 K Array marker set, and 4,720 SNPs from the Illumina Linkage III panel. Second, the entire Affymetrix marker set was typed on the same 184 individuals by two different laboratories. Finally, the Affymetrix and Illumina marker panels had 94 SNPs in common. Our teams showed that both SNPs and microsatellites can be readily used to identify pedigree errors, and that SNPs have fewer genotyping errors and a low inconsistency rate. However, a fairly high rate of no-calls, especially for the Affymetrix platform, suggests that the inconsistency rate may be higher than observed.

Alcoholism↗
PubMed2004

Analysis of candidate genes for prostate cancer.

Considerable evidence demonstrates that genetic factors are important in the development and aggressiveness of prostate cancer. To identify genetic variants that predispose to prostate cancer we tested candidate SNPs from genomic regions that show linkage to prostate cancer susceptibility and/or aggressiveness, as well as genes that show a significant difference in mRNA expression level between tumor and normal tissue. Cases had histologically verified prostate cancer. Controls were at least 65 years old, never registered a PSA above 2.5 ng/ml, always had digital rectal examinations that were not suspicious for cancer, and have no known family history of prostate cancer. Thirty-nine coding SNPs and nine non-coding SNPs were tested in up to 590 cases and 556 controls resulting in over 40,000 SNP genotypes. Significant differences in allele frequencies between cases and controls were observed for ID3 (inhibitor of DNA binding), p = 0.05, HPN (hepsin), p = 0.009, BCAS1 (breast carcinoma amplified sequence 1), p = 0.007, CAV2 (caveolin 2), p = 0.007, EMP3 (epithelial membrane protein 3), p < 0.0001, and MLH1 (mutL homolog 1), p < 0.0001. SNPs in three of these genes (BCAS1, EMP3 and MLH1) remained significant in an age-matched subsample.

Gene Frequency↗
PubMed2004

A common polymorphism in the upstream promoter region of the hepatocyte nuclear factor-4 alpha gene on chromosome 20q is associated with type 2 diabetes and appears to contribute to the evidence for linkage in an ashkenazi jewish population.

Variants in hepatocyte nuclear factor-4 alpha (HNF4 alpha), a transcription factor that influences the expression of glucose metabolic genes, have been correlated with maturity-onset diabetes of the young, a monogenic form of diabetes. Previously, in a genome scan of Ashkenazi Jewish type 2 diabetic families, we observed linkage to the chromosome 20q region encompassing HNF4 alpha. Here, haplotype-tag single nucleotide polymorphisms (htSNPs) were identified across a 78-kb region around HNF4 alpha and evaluated in an association analysis of Ashkenazi Jewish type 2 diabetic (n = 275) and control (n = 342) subjects. We found that two of nine htSNPs were associated with type 2 diabetes: a 3' intronic SNP, rs3818247 (29.2% case subjects vs. 21.7% control subjects; P = 0.0028, odds ratio [OR] 1.49) and a 5' htSNP located approximately 3.9 kb upstream of P2, rs1884614 (26.9% case subjects vs. 20.3% control subjects; P = 0.0078, OR 1.45). Testing of additional SNPs 5' of rs1884614 revealed a >10-kb haplotype block that was associated with type 2 diabetes. Conditioning on the probands' rs1884614 genotype suggested that the chromosomal region identified by the htSNP accounted for the linkage signal on chromosome 20q in families in which the proband carried at least one risk allele. Notably, the associations and the partitioned linkage profiles near P2 were independently observed in a Finnish sample, suggesting the presence of potential regulatory element(s) that may contribute to the risk for type 2 diabetes.

Alleles↗
PubMed2003

Are there mappable genes for family resemblance for the magnitude of intra-individual variation in systolic blood pressure?

BACKGROUND: The genetic regulation of variation in intra-individual fluctuations in systolic blood pressure over time is poorly understood. Analysis of the magnitude of the average fluctuation of a person's systolic blood pressure around his or her age-adjusted trend line, however, shows moderate, albeit significant, family resemblance in Cohort 1 of the Framingham Heart Study. To determine whether genomic regions affecting this phenotype could be identified, we pursued a "model-free" multipoint quantitative linkage analysis. RESULTS: Two different linkage methods revealed multiple nominally significant signals, two to four of which are "replicated" in Cohort 2. When both cohorts are assembled into extended pedigrees, three linkage signals remain nominally significant by one or both methods. CONCLUSION: Any or all of the genomic regions in the vicinity of D5S1456, D11S2359, and D20S470 may contain elements that regulate systolic blood pressure homeostasis.

Adult Children↗
PubMed2003

Genome-wide scan of brothers: replication and fine mapping of prostate cancer susceptibility and aggressiveness loci.

BACKGROUND: Substantial evidence suggests that genetic factors play an important role in both the risk of prostate cancer and its biologic aggressiveness. Here we investigate prostate cancer susceptibility and aggressiveness with genome-wide linkage analyses of affected brothers. METHODS: We first undertook a new genome-wide linkage study of 259 brothers with prostate cancer. Our analyses tested whether the proportion of marker alleles shared by brothers was correlated with disease status or Gleason score. To further clarify 11 linkage regions observed here or previously, we genotyped and analyzed an additional 101 finely spaced markers in the 259 men, and in 594 previously studied brothers, allowing for a pooled genome-wide analysis of 853 affected brothers. RESULTS: In the new study, we detected linkage to prostate cancer on chromosome 16q23 (P = 0.009), replicating previous results, and to chromosome 11q24 (P = 0.001). In the pooled analysis, the 16q23 linkage was strengthened (P = 0.0005), as was our previous linkage to chromosome 16p (P = 0.0001), and we detected linkage to chromosome 2q32 (P = 0.009). When evaluating Gleason score, our new study detected linkage to chromosome 7q32 (P = 0.0009), again replicating previous results, and to chromosomes 5p15 (P = 0.003), 9q34 (P = 0.009), 10q26 (P = 0.03), and 18p11 (P = 0.02). In the pooled analysis of Gleason score, we observed stronger linkage to chromosome 7q32 (P = 0.0002), but slightly weaker linkage to chromosomes 5q33 (P = 0.005) and 19q13 (P = 0.009) than previously reported. In addition, the new linkages to chromosomes 10q26 and 18p11 were strengthened (P = 0.0002 and P = 0.002, respectively). CONCLUSIONS: Our results provide compelling evidence for loci harboring prostate cancer susceptibility and tumor aggressiveness genes, especially on chromosomes 16q23 and 7q32.

Aged↗
PubMed2003

CDKN1A and CDKN1B polymorphisms and risk of advanced prostate carcinoma.

A multigenic model of prostate cancer susceptibility has been proposed, in which common polymorphic variants of genes, such as the androgen and vitamin D receptor, contribute to tumorigenesis. The discovery of additional genetic factors that contribute to prostate cancer risk should provide opportunities for new approaches to the detection and treatment of this common malignancy. Herein, we examined single nucleotide polymorphic variants in the 3'-untranslated region of CDKN1A (p21(cip1)) and in codon 109 of CDKN1B (p27(kip1)) for association with advanced prostate cancer in a European-American population. Ninety-six cases and 106 controls were analyzed using PCR amplification and restriction digestion assays. CDKN1A genotype was scored as CC, CT, and TT on the basis of the digestion products. The CDKN1A genotypes CT and TT were associated with an increased risk of advanced prostate carcinoma compared with the CC genotype [odds ratio (OR), 2.24; 95% confidence interval (CI), 1.02-4.95]. The CDKN1B genotype was scored as VV, VG, or GG, again on the basis of the digestion products. The CDKN1B genotype VV was also associated with an increased risk of advanced prostate carcinoma (OR, 1.95; 95% CI, 1.09-3.47). These associations were particularly strong in those patients with androgen-independent disease [OR = 2.88 (95% CI, 1.19-6.97) and 2.11 (95% CI, 1.05-4.22) for high-risk genotypes of CDKN1A and CDKN1B, respectively]. In addition, the association of CDKN1B was particularly strong in the cohort of patients under the median age of diagnosis (OR, 2.23; 95% CI, 1.08-4.59). These results suggest that in a European-American population, CDKN1A and CDKN1B variants are associated with advanced prostate cancer. Analysis of CDKN1A and/or CDKN1B genotypes may prove useful in determining which patients are at risk for developing advanced prostate carcinoma and therefore would gain the most from aggressive screening, prophylaxis, and/or treatment.

Adult↗