Biomedical subjects

Bas A J Verhage

Publications and source records attributed to Bas A J Verhage.

6 recordsLinked to original sources

PubMed2004

Site-specific familial aggregation of prostate cancer.

Over the last decade, epidemiologic evidence has accumulated in favor of a significant but heterogeneous hereditary component in prostate cancer (PC) susceptibility. In order to map and clone PC susceptibility genes, stratification of PC families into genetically homogeneous groups appears to be a key issue. Subset definition based on age at diagnosis, presumed mode of inheritance, number of affecteds per family and coaggregation of PC with other cancers has already proven successful in some studies. Previously, the finding of the coaggregation of malignancies of the central nervous system within PC families helped to link a prostate-brain cancer susceptibility gene (CAPB) to chromosome 1p36. In this study, we evaluate the risk of PC and malignancies at other sites among first-degree relatives of a large population-based group of Dutch PC patients. A population-based family case-control study was initiated that included Caucasian PC patients newly diagnosed between July 1996 and December 1999. Information on 12,575 first-degree relatives of 704 PC patients and 1,371 controls was collected through postal questionnaires and telephone interviews. All reported PC in first-degree relatives was verified through medical records. In our population, PC has a strong familial component that is reflected by a 2.9-fold increased risk (95% CI = 2.2-3.9) of PC for first-degree relatives of PC patients. This familial risk was somewhat higher among brothers (hazard ratio = 3.9; 95% CI = 2.4-6.4) compared to fathers (hazard ratio = 2.5; 95% CI = 1.7-3.6). Cancers at other sites did not coaggregate with PC. Our data suggest that familial PC, at least in this Western European population, is site-specific, not part of an inherited cancer syndrome.

Aged↗

PubMed2003

Allelic imbalance in hereditary and sporadic prostate cancer.

BACKGROUND: In this study, we evaluate the pattern of allelic imbalance (AI) in both sporadic prostate cancer (SPC) and hereditary prostate cancer (HPC) at loci that frequently show allelic imbalance in sporadic prostate cancer, or are believed to have a putative role in the disease. METHODS: DNA obtained from 35 sporadic tumors and 46 hereditary tumors were tested for AI, by using a panel of 35 microsatellite markers. RESULTS: Chromosomal regions that display high frequencies of AI (>or=30%) in HPC include 1q, 5q, 7q, 8p, 13q, 16q, 17q, 18q, and 20q. In SPC, high frequencies of AI were found at 5q, 7q, 8p, 10q, 13q. Main differences (delta >or= 20%) in AI between HPC and SPC were at 1q, 10q, 17q, 18q, and 20q. CONCLUSION: AI at the prostate cancer susceptibility loci HPC1, PCaP, and HPC20 was seen more often in HPC compared with SPC. It appears that there are marked differences in the pattern of AI between sporadic and hereditary PCa.

Aged↗

PubMed2003

Genetic susceptibility to prostate cancer: a review.

A genetic component in prostate cancer has been recognized since decades. Through numerous epidemiological and molecular biological studies, much evidence has accumulated in favor of a significant but heterogeneous hereditary component in prostate cancer (PCa) susceptibility. Since the mapping of a high-penetrant PCa susceptibility locus at 1q24-25, much attention has been paid to the identification of PCa susceptibility genes. So far, seven loci have been mapped, and at three of these loci, genes have been cloned and mutations identified. Yet their role in hereditary and sporadic disease is still under debate and probably very modest. Although research on hereditary prostate cancer has improved our knowledge of the genetic etiology of the disease, still a lot of questions remain unanswered. Here, we aim to review the genetic epidemiological and molecular biological research in the field of hereditary prostate cancer and the problems that are encountered with this research.

Chromosomes, Human, Pair 1↗

PubMed2003

Spouse controls in family case-control studies: a methodological consideration.

In case-control studies on familial aggregation of disease, spouses may be chosen as convenient controls. In this article the pros and cons of this control group are discussed. It is argued that the use of spouse controls can be time- and cost-efficient, because of easy accessibility and their ability to provide proxy data on the patients' relatives if necessary. Furthermore, with spouse controls a higher response rate and less recall bias can be expected compared to population controls. A theoretical drawback is the possibility of assortative mating related to genetic susceptibility of the disease under study. Using a simulation study it is illustrated that even strong assortative mating on a factor, which is strongly correlated with a true risk factor under study, will have a negligible effect on the observed extent of familial aggregation.

Adult↗

PubMed2003

Inherited predisposition to prostate cancer.

A genetic component in prostate cancer has been recognized for decades. Through numerous epidemiological and molecular biological studies much evidence has accumulated in favor of a significant but heterogeneous hereditary component in prostate cancer (PCa) susceptibility. At first, segregation analyses supported the view that a number of high-risk loci contributed to the observed Mendelian inheritance of PCa. Consequent mapping efforts yielded several susceptibility loci across the genome. At three of these loci genes have been cloned and mutations identified. Their role in hereditary and sporadic disease, however, is still under debate and probably very modest. The current evidence supports the hypothesis that excess familial risk of PCa is due to the inheritance of multiple moderate-risk genetic variants. Although research on hereditary prostate cancer has improved our knowledge of the genetic etiology of the disease, a lot of questions still remain unanswered. Here, we aim to review the genetic epidemiological research and the mapping efforts in the field of hereditary PCa and the consequent problems that are encountered.

Genetic Linkage↗

PubMed2002

Single-nucleotide polymorphism in the E-cadherin gene promoter modifies the risk of prostate cancer.

E-cadherin plays a major role in intercellular adhesion, cell polarity and tissue architecture. We determined the relative risk of PCa associated with a previously reported C/A SNP at -160 bp relative to the transcription-start site of the E-cadherin gene promoter. Eighty-two PCa patients and 188 controls were genotyped. Genotype and allele frequencies differed significantly among cases and controls. A-allele carriers had a higher relative risk of PCa (OR = 3.6, 95% CI 2.0-6.4) compared to C-only carriers. AC and AA genotypes had an increased risk of PCa (OR = 3.8, 95% CI 2.1-6.8 and OR = 1.7, 95% CI 0.4-6.6, respectively) compared to CC genotypes.

Aged↗