Biomedical subjects

Katja K H Aben

Publications and source records attributed to Katja K H Aben.

4 recordsLinked to original sources

PubMed2006

Segregation analysis of urothelial cell carcinoma.

A family history of urothelial cell carcinoma (UCC) confers an almost two-fold increased risk of developing UCC. It is unknown whether (part of) this aggregation of UCC has a Mendelian background. We performed complex segregation analyses on 1193 families ascertained through a proband with UCC of the bladder, ureter, renal pelvis or urethra, who were newly diagnosed between January 1, 1995 and December 31, 1997 and registered by two population-based cancer registries in the southeastern part of the Netherlands. Data were reported on 10 738 first-degree relatives by postal questionnaire; 101 of these relatives had UCC. All reported occurrences of UCC were verified (if possible) using medical records. Analyses were performed with the S.A.G.E. segregation package. Five restricted models (Mendelian dominant, Mendelian recessive, Mendelian co-dominant, 'no major gene' model and environmental model) were tested against the general unrestricted model. Sex and smoking status were incorporated as covariates. Strong evidence of Mendelian inheritance of UCC through a single major gene was not found in these 1 193 families. However, since none of the Mendelian models could be rejected, an inherited subtype of UCC cannot be excluded. A major gene may segregate in some families but this effect may have been masked in a background of high sporadic incidence. The 'no major gene' (or sporadic) model appeared to be the most parsimonious one to describe the occurrence of UCC in these families.

Female↗

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

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↗

PubMed2002

Familial aggregation of urothelial cell carcinoma.

Urothelial cell carcinoma (UCC) is not considered to be a familial disease. Familial clustering of UCC was described in several case reports, however, some with an extremely early age at onset suggesting a genetic component. Epidemiological studies yielded inconsistent evidence of familial UCC, possibly because of low power and the inability to adjust for strong confounding. In our study the existence of a familial subtype of UCC was evaluated, as well as familial clustering of UCC with other types of cancer. A population-based family case-control study was performed including patients newly diagnosed with UCC of the bladder, ureter, renal pelvis or urethra, between January 1995 and December 1997, in the southeastern part of the Netherlands. Information on the patients' first-degree relatives was collected by postal questionnaire and subsequent telephone calls. The patients' partners filled out a similar questionnaire on their relatives. All reported occurrences of UCC were verified using medical records. Disease occurrence among case-relatives and control-relatives was compared to obtain the familial risk. Random effect proportional hazards regression analyses were used to calculate this familial risk while adjusting for age, gender and smoking behavior. In 95 families of the 1,193 patients and in 36 families of the 853 partners at least 1 relative was diagnosed with UCC. This yielded an adjusted hazard ratio (HR) of 1.8 (95% CI: 1.3-2.7). An increased risk was also found for cancer of the hematolymphopoietic system (hazard ration = 1.9, 95% CI: 1.2-3.1) among case-relatives. These results indicate that UCC has a familial component with an almost 2-fold increased risk among first-degree relatives of patients with UCC, which cannot be explained by smoking. Future segregation analyses may indicate whether this clustering can be attributed to genetic susceptibility.

Adolescent↗