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Background: Long-term effects of ovarian stimulation for IVF on the risk of ovarian malignancies are unknown.Methods: We identified a nationwide historic cohort of 19,146 women who received IVF treatment in the Netherlands between 1983 and 1995, and a comparison group of 6006 subfertile women not treated with IVF. In 1997-1999, data on reproductive risk factors were obtained from 65% of women and data on subfertility (treatment) were obtained from the medical records. The incidence of ovarian malignancies (including borderline ovarian tumours) through 2007 was assessed through linkage with disease registries. The risk of ovarian malignancies in the IVF group was compared with risks in the general population and the subfertile comparison group.Results: After a median follow-up of 14.7 years, the risk of borderline ovarian tumours was increased in the IVF group compared with the general population [standardized incidence ratio (SIR) = 1.76; 95% confidence interval (CI) = 1.16-2.56]. The overall SIR for invasive ovarian cancer was not significantly elevated, but increased with longer follow-up after first IVF (P = 0.02); the SIR was 3.54 (95% CI = 1.62-6.72) after 15 years. The risks of borderline ovarian tumours and of all ovarian malignancies combined in the IVF group were significantly increased compared with risks in the subfertile comparison group (hazard ratios = 4.23; 95% CI = 1.25-14.33 and 2.14; 95% CI = 1.07-4.25, respectively, adjusted for age, parity and subfertility cause).Conclusions: Ovarian stimulation for IVF may increase the risk of ovarian malignancies, especially borderline ovarian tumours. More large cohort studies are needed to confirm these findings and to examine the effect of IVF treatment characteristics. [ABSTRACT FROM AUTHOR]

Retinoblastoma patients have a strongly increased risk of second malignancies, and survivors with a third or subsequent malignancy are increasingly observed. However, it has not been examined whether survivors who developed a second malignancy have a greater risk of a subsequent malignancy. On the basis of the Dutch retinoblastoma registry, the risk of a third malignancy was compared with cancer risk in the Dutch population. Cox model analysis with a time-dependent covariate was used to compare the subsequent malignancy risk and survival among patients with and without a second malignancy. Risk of a third malignancy was increased 8-fold compared with the general population. The hazard ratio (HR) of a third malignancy after a second malignancy was more than 7-fold increased compared to the risk of a second malignancy after retinoblastoma. Radiotherapy increased the risk 3-fold. A third malignancy was associated with worse survival compared with survival of patients only diagnosed with a second malignancy (HR=5.0). Survivors of retinoblastoma who already developed a second primary malignancy have an even higher risk of subsequent primary malignancies than retinoblastoma survivors without a second malignancy. Treating physicians and patients should be aware of this higher risk. [Copyright &y& Elsevier]

Objective: The aim of this study was to evaluate whether values of FSH, LH, estradiol, anti-Müllerian hormone (AMH), inhibin B, antral follicle count (AFC) and ovarian volume (OV) determined on day 7 of the hormone-free interval are similar to values measured on days 2-5 of two subsequent natural menstrual cycles. In addition, values measured on day 7 of the hormone-free interval were examined for the purpose of predicting values measured on days 2-5 during the second natural cycle. Methods: In this study, 25 women using hormonal contraception provided a blood sample and underwent transvaginal ultrasound measurements on day 7 of the hormone-free interval and on cycle days 2-5 of two subsequent natural cycles. Changes were compared by repeated measures ANOVA and multivariate linear regression was used for prediction purposes. Results: Mean (SD) age of the participants was 26.3 (6.2) years. Overall significant decreases in FSH and inhibin B and significant increases in AMH, AFC and ovarian volume values were measured after discontinuation of hormonal contraception (P < 0.001, P = 0.04, P = 0.01, P < 0.001 and P = 0.004, respectively). Significant changes occurred both from day 7 of the hormone-free interval to natural cycle 1 as well as from natural cycle 1 to natural cycle 2. FSH, AMH and AFC values measured during days 2-5 of natural cycle 2 could be predicted by the corresponding values measured on day 7 of the hormone-free interval. Conclusion: Hormonal and ultrasound markers of ovarian function in hormonal contraception users measured at the end of the hormone-free interval do not seem to represent subsequent natural early follicular phase values. However, these values can, in some cases (FSH, AMH and AFC), be used to predict early follicular phase values using calculated prediction equations, which need to be validated in future research. [ABSTRACT FROM AUTHOR]

Abstract: This study examined long-term cause-specific mortality among 998 Dutch retinoblastoma survivors, diagnosed from 1862 to 2005, according to follow-up time, treatment and heredity. After a median follow-up of 30.8 years, only cause-specific mortality for second malignancies among hereditary retinoblastoma survivors was statistically significantly increased with 12.8-fold. Risk of death from second malignancies among non-hereditary survivors was not increased. Mortality rates of second malignancy among hereditary patients were non-significantly elevated with 1.6-fold for treated with radiotherapy, compared to those treated otherwise. Standardised mortality ratios (SMRs) for second malignancy among hereditary patients increased during the first three decades after retinoblastoma diagnosis. Whereas these risks decreased after three decades, the absolute excess risk (AER) increased significantly, up to 23.2 excess cases per 1000 patients/year after five decades of follow-up. Fifty years after retinoblastoma diagnosis the cumulative mortality from any second malignancy was 17.3% for hereditary patients. Very long-term follow-up of retinoblastoma patients revealed an emerging excess risk of mortality in hereditary retinoblastoma survivors. This implies that lifelong follow-up is needed, whereas at the same time, patients and their physicians must be alerted to the increased second malignancy risks. [Copyright &y& Elsevier]

Abstract: As migrant studies can offer important information with regard to cancer aetiology, we estimated the cancer risk in first generation migrants using data of the Amsterdam Cancer Registry. The risk among western migrants was almost equal to the risk of the native population. Migrants from former Dutch colonies had a low cancer risk (standardised incidence ratios 0.69–0.81), while the lowest risks were observed for Turkey (0.66), Morocco (0.53) and sub-Sahara Africa (0.59). High risks in migrants from non-western countries were observed for cancer of the nasopharynx (China 51, Morocco 22), liver (China 13), gallbladder, cervix and thyroid, as well as for Kaposi’s sarcoma, Hodgkin’s lymphoma and mature T/NK-cell lymphoma. Cancer risk for breast, colorectum, lung, prostate, skin and testis was generally low. Although cancers related to infectious disease were relatively common among migrants from non-western countries, the low risks for mainly lifestyle related cancers resulted in a low overall risk. [Copyright &y& Elsevier]

Abstract: While stage is the most important factor for determining cancer survival, population-based survival data according to stage are rarely presented. We present such data for a large population diagnosed with cancer in the area covered by the Amsterdam Cancer Registry for the period 1989–2001 (n =108,251). Cases were grouped according to the TNM-classification. For all sites, a close correlation between stage at diagnosis and survival was observed. The stage-specific 5-year relative survival rate (RSR) ranged from close to 100% for stage I carcinoma of the salivary glands, thyroid, colon/rectum, skin, breast, female genitals, prostate and urethra to ⩽1% for stage IV carcinoma of the oesophagus, stomach, liver, gallbladder, pancreas and lung. Between 1989–1991 and 1999–2001, we observed an increase in the stage-specific RSR for carcinoma of colon/rectum (stages II–IV), lung (stages I–II), breast (stages I–III) and prostate (stages II–IV). Changes in diagnostic (breast, prostate) and staging procedures (lung), surgery (rectum, prostate) and adjuvant treatment (breast, colon) are likely to have contributed to this increase. [Copyright &y& Elsevier]

Smokers of cigarettes are exposed to a number of carcinogens, induding polycylic aromatic hydrocarbons (PAHs), and are at a high risk for lung cancer. PAHs exert their carcinogenic activity after metabolic activation to reactive intermediates that can damage DNA through adduct formation. Measuring DNA adducts in peripheral white blood cells (WBC) could serve as a means of monitoring human exposure to genotoxic agents and subsequently risk assessment. In this study, DNA from WBC obtained from 39 lung cancer patients was examined for PAH-DNA adducts both in an ELISA using a polyclonal antibody against benzo[]pyrene 7,8-diol-9,10-epoxide (BPDE)-DNA and the P-post-labeling technique. The ELISA results showed BPDE-DNA antigenicity in WBC DNA from 12/38 (32%) patients and adduct levels ranged from 1.5 to >150 adducts in 10 nucleotides. The autoradiographs of chromatograms of P-post-labeled digests of WBC DNA from the 38 patients showed a variety of adduct spots; relative adduct labeling (RAL) values ranged from 0.3 to 407 adducts in 10 nucleotides. In 18 of the 38 (47%) persons an adduct spot was detected that co-chromatographed with the major BPDE-DNA adduct (BPDE-dG); RAL values ranged from 0.03 to 382 adducts in 10 nucleotides. Correlations were not significant between the adduct levels in WBC and smoking habits, age or sex. From 20 patients of the same group lung tissue was collected at surgery and examined for PAH-DNA adducts by ELISA and P-post-labeling assay. No significant correlation was found between DNA adduct levels in blood and lung. This finding stresses the limitations of the use of WBC as a surrogate for adduct levels in the target organ. [ABSTRACT FROM PUBLISHER]

In an attempt to probe for polycydic aromatic hydrocarbon (PAH)-DNA adducts in human subjects resulting from smoking (or other chronic environmental exposure), lung tissue and lung tumours were obtained from patients hospitalized for lung cancer. DNA was isolated from the tissue samples and examined both in an ELISA using a polyclonal antibody against (±)-7,8-dihydroxy--9,10-epoxy-7,8,9,10-tetrahydrobenzo[]pyrene (BPDE)-DNA as well as by the nuclease P1-mediated modification of the P-post-labelling technique. The ELISA results showed BPDE–DNA antigenicity in lung DNA from 6 out of 21 patients, and adduct levels ranged from 2 to 134 adducts per 10 nucleotldes. For all 21 patients, the autoradiographs of chromatograms of P-postlabelled digests of DNA from non-tumorous lung tissue showed a strong diagonal radioactive zone (DRZ). This DRZ was generallyabsent In tumorous tissue. DNA samples that were positive in the ELISA contained a dominant spot within the DRZ that co-chromatographed with the major BPDE-DNA adduct (BPDE-dG). The quantities of the BIPE-dG spots ranged from 2.1 to 42 adducts in 10nucleotides. These values were lower than the levels found in the ELISA but correlated well with the ELISA results (Kendall = 0.97; = 0.00). The levels of the DRZ adducts ranged from 1.9 to 34 adducts in 10 nucleotides. Correlations between smoking and DNA adduct levels were poor because of the small number of current smokers ( = 13). However, smokers of filter cigarettes had significantly lower DNA adduct levels compared with smokers of cigarettes without a filter ( = 0.02 by Fischer's exact test). [ABSTRACT FROM PUBLISHER]

Background Breast cancer risk is temporarily increased after a full-term pregnancy and declines thereafter, possibly due to increased levels of gonadal and placental hormones during pregnancy. Inconsistent results, however, have been reported after twin pregnancies with higher hormone levels. Among women treated with in vitro fertilisation (IVF), for whom the number of embryos available for implantation is known, we recently observed that a multiple birth after implantation of all transferred embryos is associated with higher levels of vascular endothelial growth factor (VEGF). As VEGF is involved in breast cancer progression, we studied the effects of embryo implantation and a multiple birth on breast cancer risk in a nationwide Dutch cohort of IVF-treated women. Methods We performed a cohort analysis among 12,589 women who had been treated with IVF between 1983 and 1995 and completed a risk factor questionnaire between 1997 and 1999. Data on IVF treatment were obtained from medical records. Breast cancer cases were ascertained through linkage with the population-based Netherlands Cancer Registry. Breast cancer risks associated with singleton and multiple births were estimated with Cox regression. Findings There were 1688 women (13.4%) with multiples, 6027 (47.9%) with singletons and 4874 (38.7%) nulliparous women. Breast cancer occurred in 317 women of whom 57 had multiples. Breast cancer risk was 1.44 times higher in mothers of multiples than in mothers of singletons (95% confidence interval (CI) 1.06–1.97). Risk was highest in women who gave birth to multiples from all embryos transferred (adjusted hazard ratio (HR) 1.86, 95% CI 1.01–3.43), and lower for those with multiples after incomplete embryo implantation (adjusted HR 1.31, 95% CI 0.76–2.25). Interpretation A woman’s potential to implant all transferred embryos may be associated with breast cancer risk. Further research is needed to confirm our results and to identify the underlying biological mechanisms. [ABSTRACT FROM AUTHOR]

Aim of the study: To examine risk factors for developing hypertension in childhood cancer survivors (CCS). Methods: We conducted a nested case-control study of risk for hypertension within a cohort of 1362 childhood cancer survivors treated between 1966 and 1996 in the Emma’s Children’s Hospital/Academic Medical Center in the Netherlands. Detailed information on treatment and several lifestyle factors was collected for 44 cases with hypertension and 123 matched controls. Odds ratios (ORs) for hypertension were calculated by conditional logistic regression analysis. Results: Body Mass Index (BMI) was the only significant risk factor associated with the occurrence of hypertension (OR 3.95; 95% confidence interval (CI) 1.7–9.1 for BMI⩾25kg/m2 compared to BMI<25kg/m2). However, cisplatin, cyclophosphamide and radiotherapy (RT) to the abdominal region were all associated with non-significant risk increases (ORs of 4.3, 2.1, and 1.8, respectively). Conclusion: Our results show that BMI is the most important risk factor for hypertension following treatment of childhood cancer, emphasising the need for CCS to maintain a normal weight. [Copyright &y& Elsevier]

Abstract: Introduction: Childhood cancer survivors are known to be at increased risk for second malignancies. Patients and methods: The risk of second malignancies was assessed in 1368 5-year survivors of childhood cancer treated in the Emma Children’s Hospital AMC in Amsterdam. The median follow-up time was 16.8 years. Results: Sixty two malignancies were observed against 5.4 expected, yielding a standardised incidence ratio (SIR) of 11.2 (95% confidence interval: 8.53–14.4; absolute excess risk: 3.2 per 1000 person-years). New observations were the strongly increased risks of meningiomas (SIR=40) and basal cell carcinomas (SIR=9). Patients whose treatment involved radiotherapy had a 2-fold increased second cancer risk compared to patients with chemotherapy alone. Discussion: The relative risk of second malignancies does not decrease till at least 30 years of follow-up. With aging of the survivor cohort this results in a strong increase of the AER, due to the rising background risk of cancer with age. [Copyright &y& Elsevier]