Employment and social benefits up to 10 years after breast cancer diagnosis: a population-based study.

BACKGROUND: Little is known about employment outcomes after breast cancer (BC) beyond the first years after treatment. METHODS: Employment outcomes were compared with a general population comparison group (N=91 593) up to 10 years after BC for 26 120 patients, diagnosed before age 55 between 2000-2005, with income and social benefits data from Statistics Netherlands. Treatment effects were studied in 14 916 patients, with information on BC recurrences and new cancer events. RESULTS: BC survivors experienced higher risk of losing paid employment (Hazard Ratio (HR): 1.6, 95% Confidence Interval (95% CI) 1.4-1.8) or any work-related event up to 5-7 years (HR 1.5, 95% CI 1.3-1.6) and of receiving disability benefits up to 10 years after diagnosis (HR 2.0, 95% CI 1.6-2.5), with higher risks for younger patients. Axillary lymph node dissection increased risk of disability benefits (HR 1.5, 95% CI 1.4-1.7) or losing paid employment (HR 1.3, 95% CI 1.2-1.5) during the first 5 years of follow-up. Risk of disability benefits was increased among patients receiving mastectomy and radiotherapy (HR 1.2; 95% CI 1.1-1.3) and after chemotherapy (HR 1.7; 95% CI 1.5-1.9) during the first 5 years after diagnosis. CONCLUSIONS: BC treatment at least partly explains the increased risk of adverse employment outcomes up to 10 years after BC.

Melanoma risk after ovarian stimulation for in vitro fertilization.

STUDY QUESTION: Do women treated with ovarian stimulation for IVF have an increased risk of melanoma? SUMMARY ANSWER: Ovarian stimulation for IVF does not increase risk of melanoma, even after a prolonged follow-up. WHAT IS KNOWN ALREADY: Although exposure to ultraviolet radiation is the major risk factor for melanoma, associations between female sex steroids and melanoma risk have also been suggested. The results of available studies on fertility drugs and melanoma risk are inconclusive since most studies had several methodological limitations such as short follow-up, a small number of cases and no subfertile comparison group. STUDY DESIGN, SIZE, DURATION: In 1996, a nationwide historic cohort study (the OMEGA-cohort) was established to examine the risk of cancer after ovarian stimulation for IVF. After a median follow-up of 17 years, cancer incidence was ascertained through linkage with the Netherlands Cancer Registry. Melanoma risk in the cohort was compared with that in the general population and between the IVF group and non-IVF group using multivariable Cox regression analyses. PARTICIPANTS/MATERIALS, SETTING, METHODS: The cohort comprises 19 158 women who received IVF between 1983 and 1995 and a comparison group of 5950 women who underwent subfertility treatments other than IVF. Detailed IVF-treatment data were obtained from the medical records and complete information on parity and age at first birth was obtained through linkage with the Dutch Municipal Personal Records Database. MAIN RESULTS AND THE ROLE OF CHANCE: In total, 93 melanoma cases were observed. The risk of melanoma was not elevated among IVF-treated women, neither when compared with the general population (standardized incidence ratio = 0.89; 95% confidence interval (CI): 0.69-1.12), nor when compared with the non-IVF group (adjusted hazard ratio (HR) = 1.27; 95% CI: 0.75-2.15). A higher number of IVF cycles was associated with apparent but statistically non-significant risk increases (5-6 cycles HR = 1.92; ≥7 cycles HR = 1.79). However, no significant trend emerged. In women with more follicle stimulating hormone/human menopausal gonadotrophin ampoules comparable non-significant risk increases were found. A longer follow-up did not increase melanoma risk. Nulliparous women did not have a significantly higher melanoma risk than parous women (HR = 1.22; 95% CI: 0.81-1.84). However, women who were 30 years of age or older at first birth had a significantly higher melanoma risk than women who were younger than 30 years at first birth (age: 30-34 years HR = 4.57; 95% CI: 2.07-10.08, >34 years HR = 2.98; 95% CI: 1.23-7.21). LIMITATIONS, REASONS FOR CAUTION: Despite our large cohort, the number of melanoma cases was rather small, especially in our comparison group, which hampered subgroup analyses. WIDER IMPLICATIONS OF THE FINDINGS: Our results are reassuring for women who underwent IVF or are contemplating to start IVF. Since our cohort study is one of the largest published so far, with long-term follow-up, a subfertile comparison group, and detailed IVF-treatment data, our results add important information to the available evidence. STUDY FUNDING/COMPETING INTEREST: This study was supported by grants from the Dutch Cancer Society (NKI 2006-3631), the Health Research and Development Counsel (28-2540) and the Dutch Ministry of Health.

Treatment-specific risk of subsequent malignant neoplasms in five-year survivors of diffuse large B-cell lymphoma.

BACKGROUND: The introduction of rituximab significantly improved the prognosis of diffuse large B-cell lymphoma (DLBCL), emphasizing the importance of evaluating the long-term consequences of exposure to radiotherapy, alkylating agents and anthracycline-containing (immuno)chemotherapy among DLBCL survivors. METHODS: Long-term risk of subsequent malignant neoplasms (SMNs) was examined in a multicenter cohort comprising 2373 5-year DLBCL survivors treated at ages 15-61 years in 1989-2012. Observed SMN numbers were compared with expected cancer incidence to estimate standardized incidence ratios (SIRs) and absolute excess risks (AERs/10 000 person-years). Treatment-specific risks were assessed using multivariable Cox regression. RESULTS: After a median follow-up of 13.8 years, 321 survivors developed one or more SMNs (SIR 1.5, 95% CI 1.3-1.8, AER 51.8). SIRs remained increased for at least 20 years after first-line treatment (SIR ≥20-year follow-up 1.5, 95% CI 1.0-2.2, AER 81.8) and were highest among patients ≤40 years at first DLBCL treatment (SIR 2.7, 95% CI 2.0-3.5). Lung (SIR 2.0, 95% CI 1.5-2.7, AER 13.4) and gastrointestinal cancers (SIR 1.5, 95% CI 1.2-2.0, AER 11.8) accounted for the largest excess risks. Treatment with >4500 mg/m2 cyclophosphamide/>300 mg/m2 doxorubicin versus ≤2250 mg/m2/≤150 mg/m2, respectively, was associated with increased solid SMN risk (hazard ratio 1.5, 95% CI 1.0-2.2). Survivors who received rituximab had a lower risk of subdiaphragmatic solid SMNs (hazard ratio 0.5, 95% CI 0.3-1.0) compared with survivors who did not receive rituximab. CONCLUSION: Five-year DLBCL survivors have an increased risk of SMNs. Risks were higher for survivors ≤40 years at first treatment and survivors treated with >4500 mg/m2 cyclophosphamide/>300 mg/m2 doxorubicin, and may be lower for survivors treated in the rituximab era, emphasizing the need for studies with longer follow-up for rituximab-treated patients.

Outcomes of a population-based series of early breast cancer patients with micrometastases and isolated tumour cells in axillary lymph nodes.

BACKGROUND: Axillary lymph node staging is traditionally important to provide prognostic information to guide further treatment. However, the relevance of isolated tumour cells (ITC) or micrometastases in axillary nodes and the need for adjuvant treatment remain uncertain. PATIENTS AND METHODS: Data from 18 370 patients with pT1-2 breast cancer with pN0, pN0i+ or pN1mi were analysed. The primary end point was 5-year disease-free survival (locoregional recurrence, distant metastases or contralateral breast cancer). RESULTS: Five-year disease-free survival was 89.9% [95% confidence interval 89.5% to 90.4%]; and did not differ significantly between groups. After adjusting for prognostic factors (including treatment), patients with ITC had a comparable risk (hazard ratio = 1.12) as patients with node-negative disease, while patients with micrometastases had a 38% higher risk of recurrence. CONCLUSION(S): Patients with ITC and node-negative breast cancer appear to have similar prognosis, and those with micrometastases have a 38% higher risk of tumour recurrence. However, considering that disease-free survival is already high, we are reluctant to advise chemotherapy in all patients with ITC or micrometastases. In future, genomic tumour characteristics might predict the propensity of dissemination from the primary cancer better than the status of the axillary lymph nodes.

Breslow thickness in the Netherlands: a population-based study of 40 880 patients comparing young and elderly patients.

BACKGROUND: Melanoma incidence has increased rapidly in the last decades, and predictions show a continuing increase in the years to come. The aim of this study was to assess trends in melanoma incidence, Breslow thickness (BT), and melanoma survival among young and elderly patients in the Netherlands. METHODS: Patients diagnosed with invasive melanoma between 1994 and 2008 were selected from the Netherlands Cancer Registry. Incidence (per 100 000) over time was calculated for young (<65 years) and elderly patients (≥65 years). Distribution of BT for young and elderly males and females was assessed. Regression analysis of the log-transformed BT was used to assess changes over time. Relative survival was calculated as the ratio of observed survival to expected survival. RESULTS: Overall, 40 880 patients were included (42.3% male and 57.7% female). Melanoma incidence increased more rapidly among the elderly (5.4% estimated annual percentage change (EAPC), P<0.0001) than among younger patients (3.9% EAPC, P<0.0001). The overall BT declined significantly over time (P<0.001). Among younger patients, BT decreased for almost all locations. Among elderly males, BT decreased for melanomas in the head and neck region (P=0.001) and trunk (P<0.001), but did not decrease significantly for the other regions. Among elderly females, BT only decreased for melanomas at the trunk (P=0.01). The relative survival of elderly patients was worse compared with that of younger patients (P<0.001). CONCLUSION: Melanoma incidence increases more rapidly for elderly than for younger patients and the decline in BT is less prominent among elderly patients than among young patients. Campaigns in the Netherlands should focus more on early melanoma detection in the elderly.

Risk and prognostic significance of metachronous contralateral testicular germ cell tumours.

BACKGROUND: Testicular germ cell tumour (TGCT) patients are at increased risk of developing a contralateral testicular germ cell tumour (CTGCT). It is unclear whether TGCT treatment affects CTGCT risk. METHODS: The risk of developing a metachronous CTGCT (a CTGCT diagnosed ≥6 months after a primary TGCT) and its impact on patient's prognosis was assessed in a nationwide cohort comprising 3749 TGCT patients treated in the Netherlands during 1965-1995. Standardised incidence ratios (SIRs), comparing CTGCT incidence with TGCT incidence in the general population, and cumulative CTGCT incidence were estimated and CTGCT risk factors assessed, accounting for competing risks. RESULTS: Median follow-up was 18.5 years. Seventy-seven metachronous CTGCTs were diagnosed. The SIR for metachronous CTGCTs was 17.6 (95% confidence interval (95% CI) 13.9-22.0). Standardised incidence ratios remained elevated for up to 20 years, while the 20-year cumulative incidence was 2.2% (95% CI 1.8-2.8%). Platinum-based chemotherapy was associated with a lower CTGCT risk among non-seminoma patients (hazard ratio 0.37, 95% CI 0.18-0.72). The CTGCT patients had a 2.3-fold (95% CI 1.3-4.1) increased risk to develop a subsequent non-TGCT cancer and, consequently, a 1.8-fold (95% CI 1.1-2.9) higher risk of death than patients without a CTGCT. CONCLUSION: The TGCT patients remain at increased risk of a CTGCT for up to 20 years. Treatment with platinum-based chemotherapy reduces this risk.

A randomized phase II study investigating the addition of the specific COX-2 inhibitor celecoxib to docetaxel plus carboplatin as first-line chemotherapy for stage IC to IV epithelial ovarian cancer, Fallopian tube or primary peritoneal carcinomas: the DoCaCel study.

BACKGROUND: In ovarian cancer, cyclooxygenase-2 (COX-2) overexpression is prognostic for poor survival. We investigated the efficacy of celecoxib (C), a selective COX-2 inhibitor, added to docetaxel (Taxotere)/carboplatin (DC) in advanced ovarian cancer. PATIENTS AND METHODS: In a phase II, randomized study, 400 mg celecoxib b.i.d. was added to first-line DC treatment (DCC). Celecoxib was to be continued after DC termination up to 3 years. Study end points were tolerability, progression-free survival (PFS) and overall survival (OS). RESULTS: 151 of 196 eligible patients were diagnosed with stage IIIC/IV disease. Median follow-up for patients alive was 32.3 months. Celecoxib was used during a mean of 8.5 months. Twenty-three of 97 DCC patients stopped celecoxib prematurely, mainly due to skin reactions. Complete biochemical response was achieved in 51/78 DC patients (65%) versus 57/78 DCC patients (75%, not significant). In both study arms, median PFS was 14.3 months and median OS 34 months. COX-2 was expressed in 82% of 120 tumor samples retrospectively recovered. The PFS and OS of patients with intermediate/high COX-2 expression were similar to that in the other patients. CONCLUSION: Celecoxib did not influence PFS and OS, but interpretation of results is hampered by premature celecoxib discontinuation.

Safety and cost-effectiveness of shortening hospital follow-up after breast cancer treatment.

BACKGROUND: In the Netherlands, the first 5 years of follow-up after treatment for breast cancer are carried out in hospital with yearly mammography. After this, for patients aged over 60 years who have undergone mastectomy, there is a shift of care to the National Screening Programme (NSP) for mammography every 2 years. After breast-conserving therapy follow-up is perfomed by the general practitioner (GP), with mammography every second year and physical examination annually. The aim of this study was to evaluate the clinical effects and costs of four different strategies for follow-up after breast cancer treatment. METHODS: An extended and validated simulation model for breast cancer follow-up was used. The current guidelines for follow-up (baseline strategy) and three less intensive follow-up strategies were evaluated. The main outcome measure was the detection rate of small tumours (2 cm or smaller) and associated costs for each strategy. RESULTS: Shortening the follow-up time in hospital by shifting care to the NSP or GP after 2 years instead of 5 years of hospital follow-up, lowering the age of referral to the NSP or GP from 60 to 50 years, and termination of annual physical examination by the GP after hospital follow-up did not decrease the detection of small tumours. In addition, a substantial decrease in costs was observed with simplified follow-up. CONCLUSION: Decreasing hospital follow-up time, lowering the age of referral to the NSP or GP, and termination of annual physical examinations would lead to a substantial reduction in costs while maintaining the possibility of detecting small breast cancers.

Implementation of trastuzumab in conjunction with adjuvant chemotherapy in the treatment of non-metastatic breast cancer in the Netherlands.

Trastuzumab in conjunction with adjuvant chemotherapy markedly improves outcome. In the Netherlands, a national guideline was released in September 2005 stating that trastuzumab should be given in conjunction with adjuvant chemotherapy in women with HER2-positive breast cancer. Aim of this study was to identify the number of women with HER2-positive breast cancer and to evaluate the level of implementation of adjuvant trastuzumab in clinical practice nationwide. Women diagnosed with primary breast cancer between September 2005 and January 2007 were selected from the Netherlands Cancer Registry (NCR). HER2 status, adjuvant treatment and reasons to withhold trastuzumab were registered. 14,934 Breast cancer patients were diagnosed in this period of whom 1,928 (13%) had a HER2-positive tumour. Of all HER2-positive women receiving adjuvant chemotherapy, 66 (6%) did not receive trastuzumab. This percentage decreased from 10% at the time of introduction of the guideline to 4% in the study period September 2005-December 2006. Most common reasons to withhold trastuzumab were cardiovascular disease (29%) and patient refusal (21%). Of all HER2-positive patients who received adjuvant chemotherapy, 94% received trastuzumab. The implementation of trastuzumab in clinical practice was realized within 8 months after introduction of the new guideline.

Cancer in adolescents and young adults in north Netherlands (1989-2003): increased incidence, stable survival and high incidence of second primary tumours.

BACKGROUND: Lack of survival improvement in adolescents and young adults (AYA) with cancer has led to increased awareness of this young population. DESIGN: We carried out a population-based study of incidence and survival of primary tumours and second primary tumours in patients aged 12-24 in north Netherlands. Age-specific incidence rates per 100,000 and 3-year moving means were calculated. Factors associated with incidence and survival were assessed using a Poisson model, log-rank test and multivariate Cox proportional hazards analysis. RESULTS: From 1989 to 2003 a total of 1118 patients were diagnosed. The total age-specific incidence rates per 100,000 were as follows: males: 13.4 (12-15 years), 26.9 (16-19 years) and 27.5 (20-24 years) and females: 13.9, 20.7 and 20.7. Male : female ratio was 1.32. The overall estimated annual percentage change (EAPC) in incidence was 2.15% (P < 0.01). Five-year survival was 80.8% and did not improve during the study period. With median follow-up of 5.5 years (range 0.0-16.0) in our cohort the standardized incidence ratio (SIR) of second primary tumours was 30.55 (95% confidence interval = 19.96-44.76, P < 0.05). CONCLUSIONS: The total incidence of cancer in AYA increased (EAPC = 2.15%). Survival was unchanged. The SIR of a second primary tumour in this young cohort increased 31-fold. Further research is needed to study this increasing incidence and optimise treatment outcome in these young patients.

Pulmonary tumours in the Netherlands: focus on temporal trends in histology and stage and on rare tumours.

BACKGROUND: Recent temporal trends in histology and stage of pulmonary tumours in the Netherlands were studied. The incidence of rare pulmonary tumours was determined. METHODS: All tumours originating from the trachea, bronchus and lung recorded in the Netherlands Cancer Registry were included. Based on ICD-O morphology codes, five major subgroups were constructed: squamous carcinoma (SC), adenocarcinoma (AC), large cell (undifferentiated) carcinoma (LC), small cell lung cancer (SCLC) and other (including uncommon tumours). RESULTS: Between 1989 and 2003, 134,894 tumours were diagnosed. In men the age-adjusted incidence of SC and SCLC decreased, AC remained stable and LC increased. In women the incidence of all subgroups increased. Since 1996, a stage shift was observed with fewer patients in stage I and more patients in stage IV at diagnosis. This stage shift occurred equally in SC, AC and LC. In SC, fewer patients presented with stage IV disease than in AC and LC (25% vs 44% and 49% in 2003, respectively). The incidence of adenosquamous carcinoma decreased from 0.6 to 0.29/100 000 (p<0.001). The incidence of carcinoid tumours, sarcomatoid carcinomas and primary pulmonary sarcomas remained stable (0.44, 0.17 and 0.08/100 000, respectively). CONCLUSION: The incidence of smoking-related tumours decreased in men (especially SC and SCLC) and increased in women (all subgroups). More patients presented with stage IV disease. The incidence of non-smoking-related uncommon tumours remained constant.

Association with HLA class I in Epstein-Barr-virus-positive and with HLA class III in Epstein-Barr-virus-negative Hodgkin's lymphoma.

BACKGROUND: Associations of Hodgkin's lymphoma with HLA have been reported for many years. In 20-40% of patients with this disorder, Epstein-Barr virus (EBV) is present in the neoplastic cells. Because presentation of EBV antigenic peptides can elicit vigorous immune responses, we investigated associations of the HLA region with EBV-positive and EBV-negative Hodgkin's lymphoma. METHODS: In a retrospective, population-based study, patients with Hodgkin's lymphoma were reclassified according to the WHO classification, and EBV status was assessed by in-situ hybridisation of EBV-encoded small RNAs. Germline DNA was isolated from 200 patients diagnosed between 1987 and 2000 and from their first-degree relatives. Genotyping was done with 33 microsatellite markers spanning the entire HLA region and two single-nucleotide polymorphisms in the genes for tumour necrosis factor alpha and beta. Classic association analysis and the haplotype sharing statistic were used to compare patients with controls. FINDINGS: Classic association analysis (but not the haplotype sharing statistic) showed an association of consecutive markers D6S265 and D6S510 (p=0.0002 and 0.0003), located in the HLA class I region, with EBV-positive lymphomas. The haplotype sharing statistic (but not classic association analysis) showed a significant difference in mean haplotype sharing between patients and controls surrounding marker D6S273 (p=0.00003), located in HLA class III. INTERPRETATION: Areas within the HLA class I and class III regions are associated with susceptibility to Hodgkin's lymphoma, the association with class I being specific for EBV-positive disease. This finding strongly suggests that antigenic presentation of EBV-derived peptides is involved in the pathogenesis of EBV-involved Hodgkin's lymphoma. RELEVANCE TO PRACTICE: Polymorphisms in the HLA region could explain ethnic variation in the incidence of Hodgkin's lymphoma. The association of EBV-positive Hodgkin's lymphoma with HLA class I suggests that this polymorphism might affect the proper presentation of EBV antigens to cytotoxic T lymphocytes.

Cause-specific excess mortality in patients treated for cancer of the oral cavity and oropharynx: A population-based study.

PURPOSE: To assess cause-specific mortality in a large population-based cohort of 14,393 patients treated for squamous cell carcinoma of the oral cavity (OC) or oropharynx (OP) in The Netherlands between 1989 and 2006. PATIENTS AND METHODS: Causes of death were obtained for 94.7% of 9620 patients who had died up to January 1, 2009. We assessed standardized mortality ratios (SMR) and absolute excess mortality (AEM), comparing observed cause-specific mortality with expected mortality for our cohort based on general population mortality rates. RESULTS: Median survival was 3.9 years. Overall, the study population experienced a 6-fold higher (95% Confidence Interval (95% CI) 5.9-6.1) mortality risk compared with the general population. After three years, 41% of OP and 29% of OC patients had died due to cancer of the oral cavity and pharynx. Additionally, OC and OP patients experienced high excess mortality from esophageal (SMR 10.6 and 17.9) and lung cancer (SMR 4.6 and 6.3). With regard to non-cancer deaths, the highest AEMs were due to diseases of the circulatory system, with OC patients experiencing an AEM of 11.3 per 10,000 person-years for ischemic heart disease. OP patients experienced excess mortality due to pneumonia (AEM 22.1 per 10,000 person-years). The risk of death due to diseases of the digestive system was for OP and OC patients where about equal (AEM 28.7 and 23.80, respectively). The SMR for death due to pneumonia was more than two times higher (4.4 vs. 1.7) for OP patients than for OC patients (P<0.001). From 15 years after diagnosis, second tumors located outside the head and neck region accounted for most of the excess mortality. CONCLUSIONS: Excess mortality in OC and OP patients appears to be dominated by effects of heavy tobacco and alcohol use with high AEM due to second tumors, respiratory, cardiovascular and gastrointestinal diseases. Patients with OP experienced more than two times higher risk of death due to pneumonia than OC patients. Therefore, awareness of this potential complication should be raised along with development of prevention strategies.

Long-term risk of second malignancy in survivors of Hodgkin's disease treated during adolescence or young adulthood.

PURPOSE: To quantify the long-term risk of second primary cancers (SCs) in patients diagnosed with Hodgkin's disease (HD) during adolescence or young adulthood. PATIENTS AND METHODS: The risk of SCs was assessed in 1,253 patients diagnosed with HD before the age of 40 years and treated in two Dutch cancer centers between 1966 and 1986. The median follow-up duration was 14.1 years. RESULTS: In all, 137 patients developed SCs, compared with 19.4 cases expected on the basis of incidence rates in the general population (relative risk [RR] = 7.0; 95% confidence interval, 5.9 to 8.3). The 25-year actuarial risk of SC overall was 27.7%. The RR of solid tumors increased greatly with younger age at the first treatment of HD, not only for breast cancer but also for all other solid tumors, with RRs of 4.9, 6.9, and 12.7 for patients first treated at ages 31 to 39 years, 21 to 30 years, and

Soft tissue sarcoma: why not treated?

BACKGROUND: Soft tissue sarcomas (STS) are uncommon malignancies and elderly STS patients have been reported to receive less definitive treatment compared to young STS patients. The present study was performed to investigate whether withholding treatment was based on disease specific aspects, patients' general health condition, comorbidity or a combination of these. METHODS: Patients with primary STS, registered by the Comprehensive Cancer Center North-Netherlands (CCCN) from 1989 to 1999, were analyzed retrospectively with regard to the inclusion-criteria: no primary anti-tumor treatment. RESULTS: From 1989 to 1999, 620 patients (including 56 Kaposi sarcoma) were registered with primary STS. Seventy-six patients (13%) were registered as untreated. Nineteen patients were excluded. Records of 57 patients, median age 71 years (range 23-92, 40 patients > or =65 years, 17 patients < 65 years) were examined. The reasons for no treatment were irresectability of the sarcoma (65%), metastatic disease (11%), comorbidity (4%), poor general health (5%), death prior to therapy (7%) and refusal of therapy (3%) (motivation not documented in 5%). CONCLUSIONS: Thirteen percent of all STS patients within the CCCN region were not treated, 70% of these patients were elderly. Withholding treatment was mostly disease-related (76%), e.g. irresectable retroperitoneal STS or metastatic disease; for 19% of the patients, it was related to their poor general health. The decision to refrain from cancer treatment was justifiable in all these STS patients.

Genes other than BRCA1 and BRCA2 involved in breast cancer susceptibility.

This review focuses on genes other than the high penetrance genes BRCA1 and BRCA2 that are involved in breast cancer susceptibility. The goal of this review is the discovery of polymorphisms that are either associated with breast cancer or that are in strong linkage disequilibrium with breast cancer causing variants. An association with breast cancer at a 5% significance level was found for 13 polymorphisms in 10 genes described in more than one breast cancer study. Our data will help focus on the further analysis of genetic polymorphisms in populations of appropriate size, and especially on the combinations of such polymorphisms. This will facilitate determination of population attributable risks, understanding of gene-gene interactions, and improving estimates of genetic cancer risks.

The epidemiology of head and neck squamous cell carcinoma in The Netherlands during the era of HPV-related oropharyngeal squamous cell carcinoma. Is there really evidence for a change?

BACKGROUND: Several recent studies have shown that incidence of oropharyngeal carcinomas is rising in the Western World. This increase has been attributed to changes in the etiology of oropharyngeal carcinomas with a growing role for infections with Human Papilloma viruses. This nationwide study evaluates and compares trends in incidence, clinical behavior and tumor characteristics of oropharyngeal and oral squamous cell cancer. METHODS: This study comprised all 16,480 patients with primary squamous cell carcinoma of the oral tongue (OTSCC), oral cavity excluding oral tongue (OCSCC), and oropharynx (OPSCC) diagnosed from 1989 through 2008 in The Netherlands. We assessed trends in age-standardized incidence, second cancer risk and subsite specific relative survival (RS) over time. RESULTS: Incidence of OTSCC and OPSCC in males and incidence of all subsites in females increased significantly from 1989 through 2008. In males increases in incidence were largely restricted to the 50-64 year age group (estimated annual percentage change 2.2% and 3.2% for OTSCC and OPSCC, respectively), while in females incidence increased for most age groups. The incidence of OCSCC (excl. oral tongue) and OPSCC before 50 years of age decreased. Patients with OPSCC showed the poorest prognosis with a relative survival of 41.6% after 5 years and 29.4% after 10 years (P<0.001) over the entire period 1989-2008. However survival increased substantially for OPSCC patients over time (5-year RS of 37.2% in 1989-1993 to 47.6% in 2004-2008, P<0.001). CONCLUSION: Although incidence of OPSCC did increase since 1989, especially in females, similar increases were seen for OCSCC (excl. oral tongue) and OTSCC. Our study does not appear to support that HPV is the main contributor to a rising incidence of OPSCC as the effects of changes in smoking and alcohol use cannot be discounted.

Epidemiological aspects of soft tissue sarcomas (STS)--consequences for the design of clinical STS trials.

The purpose of the study was to gain insight into epidemiological aspects of soft tissue sarcomas (STS), based on the population-based cancer registry of the Comprehensive Cancer Center North-Netherlands (CCCN), and to provide data for the development of future STS clinical trials. 456 primary STS (Kaposi, urogenital and gastro-intestinal STS excluded), registered from 1989 to 1995 by the cancer registration of the Comprehensive Cancer Center North-Netherlands (CCCN), were analysed. The annual, age-adjusted, STS incidence was 3.6 per 100,000. Incidence increased with age. Half of the patients were over the age of 65 years. Malignant fibrous histiocytomas and liposarcomas were most frequently encountered. At presentation, nodal involvement was rare (3-8%). Distant metastases were more frequently encountered (9-14%), and appeared to be related to tumour size and site. Above 70 years of age, 16% of patients received no treatment at all, especially for metastatic disease.

Epidemiology of cancer of the lip in The Netherlands.

Descriptive epidemiological data of new cases of squamous cell carcinoma of the vermilion border of the lip in the Netherlands from 1989-94 inclusive are presented. Lip cancer represented 0.47 and 0.09% of all new malignancies in males and females, respectively. The lower lip was the most frequently affected site. The majority of the lip cancers were diagnosed in tumour stage I. The median age at diagnosis in males was 68 years, 5 years less than in females. The overall male-to-female ratio was 5.7. Age-adjusted incidence rates in males and females were 2.2 and 0.3 per 100,000 (ESR), respectively. The cumulative lifetime risk for developing lip cancer was 0.15 for males and 0.03 for females. Mortality/incidence ratios in males and females were 0.05 and 0.07, respectively. Differences in lip cancer incidence were observed between an urban and a rural area. There was a positive association between the occurrence of lip cancer and rural residence; rate ratios were 3.3 among males and 3.5 among females.

No association between the Arg201Gly polymorphism of the DCC gene and colorectal cancer.

BACKGROUND AND AIMS: In one small study, the DCC Arg201Gly polymorphism has been observed more frequently in colorectal cancer cases compared with controls. We wondered whether these results could be replicated in a much larger study. METHODOLOGY: The DCC Arg201 Gly polymorphism was genotyped in 625 unselected Caucasian colorectal cancer patients and 220 controls. Association analysis was used to search for a difference between patients and controls. Subgroup analyses were performed for site of tumour, gender, age at diagnosis, family history of colorectal cancer and modified Dukes classification. RESULTS: The association analyses revealed no difference in Arg201Gly genotype frequency between patients and controls, neither overall nor for different subgroups according to site of tumour, gender, age at diagnosis, family history of colorectal cancer and modified Dukes classification. CONCLUSION: No association was observed between the Arg201Gly polymorphism of DCC and colorectal cancer risk.