Biomedical subjects

Brian K Suarez

Publications and source records attributed to Brian K Suarez.

22 records · Page 2Linked to original sources

PubMed2003

Prostate cancer aggressiveness locus on chromosome segment 19q12-q13.1 identified by linkage and allelic imbalance studies.

Whole-genome scan studies recently identified a locus on chromosome segments 19q12-q13.11 linked to prostate tumor aggressiveness by use of the Gleason score as a quantitative trait. We have now completed finer-scale linkage mapping across this region that confirmed and narrowed the candidate region to 2 cM, with a peak between markers D19S875 and D19S433. We also performed allelic imbalance (AI) studies across this region in primary prostate tumors from 52 patients unselected for family history or disease status. A high level of AI was observed, with the highest rates at markers D19S875 (56%) and D19S433 (60%). Furthermore, these two markers defined a smallest common region of AI of 0.8 Mb, with 15 (29%) prostate tumors displaying interstitial AI involving one or both markers. In addition, we noted a positive association between AI at marker D19S875 and extension of tumor beyond the margin (P = 0.02) as well as a higher Gleason score (P = 0.06). These data provide strong evidence that we have mapped a prostate tumor aggressiveness locus to chromosome segments 19q12-q13.11 that may play a role in both familial and non-familial forms of prostate cancer.

Aged↗

PubMed2003

Genetics of prostate cancer.

Prostate cancer is the most frequently diagnosed visceral cancer of men, responsible for approximately 40,000 deaths in adult males per year. To identify the genetic causes of prostate cancer, we performed a whole genome scan of affected sib pairs, using DNA markers spaced evenly across the human genome. We demonstrated that regions on chromosomes 1, 4, 5, 7, 8, 11, 16 and 19 might harbor genes that predispose individuals to prostate cancer and may affect tumor growth rate and tumor aggressiveness. Here we present DNA sequence analysis of KIAA 0872 and 17-beta hydroxysteroid dehydrogenase that are located on chromosome 16 within the mapped region, and we demonstrate that neither of these genes carries mutations in the protein coding region or their splice junction sites. These results suggest that these genes are less likely to be associated with the cause of familial prostate cancer.

17-Hydroxysteroid Dehydrogenases↗

PubMed2002

A perspective on epistasis: limits of models displaying no main effect.

The completion of a draft sequence of the human genome and the promise of rapid single-nucleotide-polymorphism-genotyping technologies have resulted in a call for the abandonment of linkage studies in favor of genome scans for association. However, there exists a large class of genetic models for which this approach will fail: purely epistatic models with no additive or dominance variation at any of the susceptibility loci. As a result, traditional association methods (such as case/control, measured genotype, and transmission/disequilibrium test [TDT]) will have no power if the loci are examined individually. In this article, we examine this class of models, delimiting the range of genetic determination and recurrence risks for two-, three-, and four-locus purely epistatic models. Our study reveals that these models, although giving rise to no additive or dominance variation, do give rise to increased allele sharing between affected sibs. Thus, a genome scan for linkage could detect genomic subregions harboring susceptibility loci. We also discuss some simple multilocus extensions of single-locus analysis methods, including a conditional form of the TDT.

Alleles↗

PubMedDate not supplied

Prostate cancer aggressiveness locus on chromosome 7q32-q33 identified by linkage and allelic imbalance studies.

The biologic aggressiveness of prostate tumors is an important indicator of prognosis. Chromosome 7q32-q33 was recently reported to show linkage to more aggressive prostate cancer, based on Gleason score, in a large sibling pair study. We report confirmation and narrowing of the linked region using finer-scale genotyping. We also report a high frequency of allelic imbalance (AI) defined within this locus in a series of 48 primary prostate tumors from men unselected for family history or disease status. The highest frequency of AI was observed with adjacent markers D7S2531 (52%) and D7S1804 (36%). These two markers delineated a common region of AI, with 24 tumors exhibiting interstitial AI involving one or both markers. The 1.1-Mb candidate region contains relatively few transcripts. Additionally, we observed positive associations between interstitial AI at D7S1804 and early age at diagnosis (P=.03) as well as a high combined Gleason score and tumor stage (P=.06). Interstitial AI at D7S2531 was associated with a positive family history of prostate cancer (P=.05). These data imply that we have localized a prostate cancer tumor aggressiveness loci to chromosome 7q32-q33 that is involved in familial and nonfamilial forms of prostate cancer.

Aged↗