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Geertruida H de Bock

Publications and source records attributed to Geertruida H de Bock.

11 recordsLinked to original sources
PubMed2006

A biological question and a balanced (orthogonal) design: the ingredients to efficiently analyze two-color microarrays with Confirmatory Factor Analysis.

BACKGROUND: Factor analysis (FA) has been widely applied in microarray studies as a data-reduction-tool without any a-priori assumption regarding associations between observed data and latent structure (Exploratory Factor Analysis).A disadvantage is that the representation of data in a reduced set of dimensions can be difficult to interpret, as biological contrasts do not necessarily coincide with single dimensions. However, FA can also be applied as an instrument to confirm what is expected on the basis of pre-established hypotheses (Confirmatory Factor Analysis, CFA). We show that with a hypothesis incorporated in a balanced (orthogonal) design, including 'SelfSelf' hybridizations, dye swaps and independent replications, FA can be used to identify the latent factors underlying the correlation structure among the observed two-color microarray data. An orthogonal design will reflect the principal components associated with each experimental factor. We applied CFA to a microarray study performed to investigate cisplatin resistance in four ovarian cancer cell lines, which only differ in their degree of cisplatin resistance. RESULTS: Two latent factors, coinciding with principal components, representing the differences in cisplatin resistance between the four ovarian cancer cell lines were easily identified. From these two factors 315 genes associated with cisplatin resistance were selected, 199 genes from the first factor (False Discovery Rate (FDR): 19%) and 152 (FDR: 24%) from the second factor, while both gene sets shared 36. The differential expression of 16 genes was validated with reverse transcription-polymerase chain reaction. CONCLUSION: Our results show that FA is an efficient method to analyze two-color microarray data provided that there is a pre-defined hypothesis reflected in an orthogonal design.

Antineoplastic Agents, Alkylating↗
PubMed2006

Sick leave as a predictor of job loss in patients with chronic arthritis.

OBJECTIVES: To study the occurrence and duration of sick leave as potential risk factors for permanent job loss after 24 months among 112 individuals with chronic arthritis and a disease related problem at work. METHODS: Data collection was embedded in a multicentre randomised controlled trial in which the cost-effectiveness of a multidisciplinary job retention vocational rehabilitation programme for employees with chronic arthritis and a disease related problem at work was compared to usual outpatient care. Sick leave (complete or partial) was defined as absenteeism reported to the employer and permanent job loss as receiving a full work disability pension or unemployment. The association between sick leave at baseline and job loss after 24 months was investigated by multivariate logistic regression analysis, including those variables that were univariately significantly associated with job loss after 24 months. RESULTS: At baseline, 60 of the 112 subjects (54%) were on sick leave, with a mean duration of 18.7 weeks, in half of these patients the sick leave was complete. After 24 months, 26 of the 112 patients (23%) had lost their job. The presence of complete sick leave (OR 4.74, 95% CI 1.86-12.07) and the depression score of the hospital anxiety and depression scale (OR 1.18, 95% CI 1.02-1.36) were significantly and independently associated with job loss after 2 years follow-up. CONCLUSION: The occurrence of complete sick leave was found to be an independent risk factor for job loss in patients with chronic arthritis who have a disease related problem at work.

Adult↗
PubMed2006

Patterns and frequency of recurrences of squamous cell carcinoma of the vulva.

OBJECTIVE: To analyze patterns and frequency of recurrences of squamous cell carcinoma (SCC) of the vulva after wide local excision (WLE) and superficial inguinal lymphadenectomy with separate incisions and to identify prognostic factors for the development of recurrences. METHODS: Between January 1985 and December 1999, all 125 consecutive patients with primary SCC of the vulva, treated with WLE and superficial inguinal lymphadenectomy, were retrospectively analyzed. Recurrences were registered by localization as: local, skin bridge, groin or distant. RESULTS: A local recurrence was diagnosed in 29 (23%) patients, 11 (9%) developed a groin and 4 (3%) a distant recurrence. No skin bridge recurrences were identified. The 5 years local relapse-free survival was 70%. After a first local recurrence, 72% of these patients developed a second local recurrence. Adjusted for other predictors, older age (>74 years) is an independent risk factor for local recurrences (HR: 2.38; 95%-C.I.: 1.08-5.23) and stage III/IV cancer for developing groin/distant recurrences (HR: 3.03; 95%-C.I.: 1.0-9.18). CONCLUSION: WLE and superficial inguinal lymphadenectomy with separate incisions result in a high groin recurrence rate in this study; superficial lymphadenectomy should be replaced by deep inguinofemoral lymphadenectomy. After a local recurrence, 72% of the patients developed a second local recurrence. These patients are at high risk and need a close follow-up.

Adult↗
PubMed2006

MUTYH and the mismatch repair system: partners in crime?

Biallelic germline mutations of MUTYH-a gene encoding a base excision repair protein-are associated with an increased susceptibility of colorectal cancer. Whether monoallelic MUTYH mutations also increase cancer risk is not yet clear, although there is some evidence suggesting a slight increase of risk. As the MUTYH protein interacts with the mismatch repair (MMR) system, we hypothesised that the combination of a monoallelic MUTYH mutation with an MMR gene mutation increases cancer risk. We therefore investigated the prevalence of monoallelic MUTYH mutations in carriers of a germline MMR mutation: 40 carriers of a truncating mutation (group I) and 36 of a missense mutation (group II). These patients had been diagnosed with either colorectal or endometrial cancer. We compared their MUTYH mutation frequencies with those observed in a group of 134 Dutch colorectal and endometrial cancer patients without an MMR gene mutation (0.7%) and those reported for Caucasian controls (1.5%). In group I one monoallelic MUTYH mutation was found (2.5%). In group II five monoallelic germline MUTYH mutations were found (14%), four of them in MSH6 missense mutation carriers (20%). Of all patients with an MMR gene mutation, only those with a missense mutation showed a significantly higher frequency of (monoallelic) MUTYH mutations than the Dutch cancer patients without MMR gene mutations (P = 0.002) and the published controls (P = 0.001). These results warrant further study to test the hypothesis of mutations in MMR genes (in particular MSH6) and MUTYH acting together to increase cancer risk.

Adaptor Proteins, Signal Transducing↗
PubMed2006

Estimation and prediction in a multi-state model for breast cancer.

An important aim in clinical studies in oncology is to study how treatment and prognostic factors influence the course of disease of a patient. Typically in these trials, besides overall survival, also other endpoints such as locoregional recurrence or distant metastasis are of interest. Most commonly in these situations, Cox regression models are applied for each of these endpoints separately or to composite endpoints such as disease-free survival. These approaches however fail to give insight into what happens to a patient after a first event. We re-analyzed data of 2795 patients from a breast cancer trial (EORTC 10854) by applying a multi-state model, with local recurrence, distant metastasis, and both local recurrence and distant metastasis as transient states and death as absorbing state. We used an approach where the clock is reset on entry of a new state. The influence of prognostic factors on each of the transition rates is studied, as well as the influence of the time at which intermediate events occur. The estimated transition rates between the states in the model are used to obtain predictions for patients with a given history. Formulas are developed and illustrated for these prediction probabilities for the clock reset approach.

Biometry↗
PubMed2006

Breast cancer screening, outside the population-screening program, of women from breast cancer families without proven BRCA1/BRCA2 mutations: a simulation study.

PURPOSE: We assessed the cost-effectiveness of mammography screening for women under the age of 50, from breast cancer families without proven BRCA1/BRCA2 mutations, because current criteria for screening healthy women from breast cancer families are not evidence-based. METHODS: We did simulation studies with mathematical models on the cost-effectiveness of mammography screening of women under the age of 50 with breast cancer family histories. Breast cancer screening was simulated with varying screening intervals (6, 12, 18, and 24 months) and screening cohorts (starting at ages 30, 35, 40, and 45, and continuing to age 50). Incremental costs of screening were compared with those of women ages 50 to 52 years, the youngest age group currently routinely screened in the nationwide screening program of the Netherlands, to determine cost-effectiveness. Sensitivity analyses were done to explore the effects of model assumptions. The cost-effectiveness of breast cancer screening for women over the age of 50 was not debated. RESULTS: The most effective screening interval was found to be 12 months, which, however, seems only to be cost-effective in a small group of women under the age of 50 with at least two affected relatives, including at least one affected in the first degree diagnosed under the age of 50. Significantly, early breast cancer screening never seemed to be cost-effective in women with only one affected first-degree or second-degree relative. CONCLUSION: Annual breast cancer screening with mammography for women under the age of 50 seems to be cost-effective in women with strong family histories of breast cancer, even when no BRCA1/BRCA2 mutation was found in affected family members.

Adult↗
PubMed2003

Automated analysis of multiple sections for the detection of occult cells in lymph nodes.

PURPOSE: At present, reverse transcription (RT)-PCR against carcino-embryonic antigen mRNA is one of the few research tools for the detection of occult cells in histopathologically assessed negative lymph nodes from patients with colorectal cancer. The aim of this study was to investigate the suitability of supervised low-resolution image analysis of immunohistochemically stained sections as alternative. EXPERIMENTAL DESIGN: Multiple sections (n = 50) of regional lymph nodes from patients with colorectal cancer were immunohistochemically stained and analyzed by applying low-resolution image analysis (flatbed scanning) for semiautomated detection of cytokeratin (CK)-positive stained cells. The sensitivity of this approach was demonstrated for 20 patients with stage II colorectal cancer and compared with RT-PCR regarding the detection of clinically assessed recurrence of disease within 10 years. RESULTS: CK(+) cells were detected in all of the patients (n = 6; 100%) with recurrence, compared with five patients (83%) found positive by carcinoembryonic antigen RT-PCR. From patients (n = 14) who did not develop a recurrence, eight (57%) had positive lymph nodes. In all patients with recurrence, we visually identified at least one group of CK(+) cells (>/==" BORDER="0">2 cells). CONCLUSIONS: Automated image analysis is a promising tool for the detection of occult cells in histopathologically negative nodes. It is potentially more sensitive but less specific for detecting recurrence of disease than conventional histopathology or RT-PCR and is particularly useful for the evaluation of sentinel nodes. Furthermore, it opens new ways for basic research of occult cells based on molecular profiling after laser-microdissection.

Automation↗
PubMed2003

Saline contrast hysterosonography in abnormal uterine bleeding: a systematic review and meta-analysis.

OBJECTIVE: To assess the diagnostic accuracy of saline contrast hysterosonography in the evaluation of the uterine cavity in women complaining of abnormal uterine bleeding. DESIGN: A systematic review and meta-analysis of diagnostic studies that compared saline contrast hysterosonography to a gold standard diagnosis based on either hysteroscopy with or without histological sampling or to hysterectomy. SETTING: University Hospital. SAMPLE: Twenty-four studies (including 2278 procedures). METHODS: Electronic databases were searched for relevant studies and references were cross checked. Validity was assessed and data were extracted independently by two authors. Heterogeneity was calculated, studies were plotted in an ROC area and data were pooled. Subgroup analysis was performed according to the validity area. MAIN OUTCOME MEASURES: The success rate of saline contrast hysterosonography. The pooled sensitivity, specificity, likelihood ratio's and post-test probabilities of saline contrast hysterosonography on the prediction of uterine cavity abnormality. RESULTS: The largest population of homogeneous data were the studies with complete verification. In these studies, the pooled sensitivity and pooled specificity of saline contrast hysterosonography in uterine cavity evaluation were respectively 0.95 (95% CI 0.93 to 0.97) and 0.88 (95% CI 0.85 to 0.92), the likelihood ratios were respectively 8.23 (95% CI 6.2 to 11) and 0.06 (95% CI 0.04 to 0.09) and the post-test probabilities were respectively 0.91 (95% CI 0.89 to 0.94) and 0.07 (95% CI 0.04 to 0.10). The overall success rate of saline contrast hysterosonography was 93% (95% CI 92% to 94%). The feasibility of saline contrast hysterosonography in postmenopausal women (success rate 86.5%, 95% CI 83.2 to 89.8) is significantly lower (P < 0.01) compared with premenopausal women (success rate 95%, 95% CI 94% to 96%). CONCLUSION: Saline contrast hysterosonography is accurate in the evaluation of the uterine cavity in pre- and postmenopausal women suffering from abnormal uterine bleeding. The feasibility of saline contrast hysterosonography is high, although significantly better in premenopausal women compared with postmenopausal women. We conclude that saline contrast hysterosonography, in combination with an endometrium aspiration if necessary, can become the standard diagnostic procedure in women with abnormal uterine bleeding.

Contrast Media↗
PubMed2003

Modeling familial clustered breast cancer using published data.

The purpose of this research was to model the familial clustering of breast cancer and to provide an accurate risk estimate for individuals from the general population, based on their family history of breast and ovarian cancer. We constructed a genetic model as an extension of a model by Claus et al. (E. B. Claus et al., Am. J. Hum. Genet., 48: 232-242, 1991), with three breast cancer genes, BRCA1, BRCA2, and a hypothetical BRCAu, in two variants, one in which BRCAu was dominant and one in which BRCAu was recessive. The model parameters were estimated using published estimates of population incidence and relative risks. Risk estimation was performed for a set of 196 counselees and for a set of simulated counselees with both the dominant BRCAu and the recessive BRCAu model, and compared relating to medical management. Estimates of the model parameters were found. Relative risks among family members were comparable between the model of Claus et al. (E. B. Claus et al., Am. J. Hum. Genet., 48: 232-242, 1991) and our model. The dominant and the recessive model provided approximately similar lifetime risks for breast cancer. Our model is suitable for breast cancer risk estimation in a health care setting.

Adult↗