Introduction 1 2 3 4 5 6 7 8 9 10 1 11 Table 1 11 Revised Bethesda-guidelines age ≤50 a <60 years b a first degree relative Three relatives one patient needs to be a first degree relative a b 12 Patients and methods We selected patients who were diagnosed with a primary and invasive colorectal tumour in the period 1999–2001 from the Cancer Registry (CR) of the Comprehensive Cancer Centre West (CCCW) in The Netherlands. The patients had to satisfy one of the following two Bethesda guidelines: the patient had to have more than one tumour, i.e., one colorectal carcinoma and a second one (colorectal cancer or another HNPCC-associated kind of tumour), or the patient had to be fifty years or younger at diagnosis. The selected patients were considered to have an indication for the performance of MSI-analysis and/or referral to the Clinical Genetic Centre (CGC). Patients with a carcinoma in situ or a carcinoïd of the appendix were not included in the analysis. Between 1999 and 2001, 434 patients who complied with the above mentioned criteria were diagnosed with CRC in one of the twelve hospitals in the CCCW-region. Seven hospitals gave permission for the collection of information concerning family history, MSI-analysis and referral to the CGC. We extracted this information from the various (electronic) medical reports. The family history was considered complete if the medical records reported on cancer in the family, and if so, information about the age at the time of the diagnosis, the type of cancer and the occurrence of cancer within first-degree and second-degree family members. Data were collected of 244 patients. Of these patients, 120 patients had multiple tumours, 109 patients were fifty years or younger at the time of diagnosis, and 15 patients had both characteristics. For comparisons between patients with multiple tumours and patients who were young at diagnosis, those with both characteristics were allocated to the “multiple tumours” group. The data were analyzed using SPSS statistical software (version 12.0.1). Univariate comparisons of proportions between patient groups were performed by Chi-squared test. Multivariate logistic regression analysis was used to study whether the presence of a complete family history or referral to a CGC could be explained by age, sex, inclusion criterion (multiple tumours or young age at diagnosis), hospital or type of medical specialist. Results The study group consisted of 244 persons, who complied with one of the Bethesda guidelines and therefore were considered to be referred for MSI-analysis and/or genetic counselling. The male:female ratio was 49:51 and did not differ between the groups selected on the basis of multiple tumours or age ≤50 years at diagnosis. A complete family history was recorded in the medical records of 38 (16%) of the 244 patients. For 136 patients (55%) limited information on the family history was available, and for 70 (29%) patients no information on the family history was found in the medical records. In the seven participating hospitals, a family history was reported for 38–91% of the patients. P 2 P 2 Table 2 Diagnostic work-up for HNPCC in 244 patients with colorectal cancer, by completeness of the family history as reported in the medical records Diagnostic workup n n n Referred to CGC 20 (53%) 17 (13%) 3 (4%) MSI-analysis performed 13 (34%) 8 (6%) 1 (1%) Results of MSI-analysis 3 MSI, 10 stable 7 stable, 1 unknown 1 stable Diagnosis of HNPCC 6 (16%) 3 (2%) 1 (1%) Discussion We used the Bethesda-guidelines to select a group of patients with a suspicion of HNPCC. These patients were diagnosed with colorectal cancer between 1999 and 2001, a period during which MSI-analysis and the Bethesda guidelines were already available. Therefore we expected that for these patients, physicians would have examined and reported their patients’ family history and that MSI-analysis would have been performed. In our study group, however, the family history of the patients diagnosed with colorectal carcinoma was not sufficiently examined and reported in the medical records. For this reason, we believe the Bethesda-guidelines were not sufficiently applied by the physicians. As a consequence, MSI-analysis was performed on a small proportion of the tumours. More patients with a complete family history in their medical records were referred by their physicians to the CGC than patients without such a family history. MSI-analysis was also performed more often in this group. We expect that in a low-risk population, i.e., patients with colorectal cancer who do not meet the Bethesda guidelines, these results would be even more dramatic. On the one hand, our results may appear to be better than they actually are. We collected our data using medical records from various medical specialties, while the treating physician will not have this overview in practice. On the other hand, it is possible that when a physician examined a family history and none of the family members was diagnosed with cancer, he did not report it in the medical records. In this case, the family history was considered as absent, although it in fact was examined. Nevertheless we expect that if MSI-analysis was performed or the patient was referred to the CGC, this would have certainly been reported. We found that the attention for HNPCC in the diagnostic workup for CRC differed widely. For the seven participating hospitals, the proportion of patients with a reported family history on cancer ranged from 38% to 91%. Furthermore, only half of the approached hospitals were willing to cooperate. For these reasons, we cannot generalise our results for the whole CCCW-region. Nevertheless, we conclude that the family history appears to be neglected in the majority of patients with colorectal cancer in our study period, and that MSI-analysis was only performed in a small proportion of the patients that meet the guidelines for this analysis. Possibly, the attention for identification of patients with HNPCC has increased in more recent years. Our findings underscore the importance of implementation of family history and Bethesda guidelines in the physician education.