Antidepressant drugs and risk of developing glioma: a national registry-based case control study and a meta-analysis.

The aim of the present study was to investigate if use of antidepressants is related to the risk of developing lower (WHO grade 2-3) and higher grade (WHO grade 4) glioma. A registry-based case-control study was performed using 1283 glioma cases and 6400 age-, sex- and geographically matched controls, diagnosed in Sweden 2009-2013. Conditional logistic regression was used to analyze whether Selective Serotonin Reuptake Inhibitors (SSRIs) or non-SSRIs were associated with the risk of developing lower- or higher-grade glioma in the study population. Our results show that use of antidepressant medication was not associated with the risk of developing glioma. We also performed a meta-analysis in which the dataset from the present study was combined with results from two previous epidemiological studies to answer the same questions. The meta-analysis showed a modest risk reduction of developing glioma in relation to antidepressant treatment (OR 0.90 [95% CI 0.83-0.97]), when all glioma subgroups and all forms of antidepressant medications were combined. In conclusion, it remains possible that antidepressants may have common monoaminergic mechanism(s) that reduce the risk of developing glioma.

Antidepressants and survival in glioma-A registry-based retrospective cohort study.

Background: Depression and treatment with antidepressant medication is common in patients with malignant glioma. However, the extent to which antidepressants may affect the disease is not fully understood. Therefore, the purpose of the present study was to investigate possible associations between treatment with antidepressant medication and survival in glioma patients. Methods: We performed a registry-based cohort study including 1231 patients with malignant glioma (WHO grades 2, 3, and 4) having undergone surgery, and 6400 matched controls without glioma. All data were extracted from the RISK North database, which contains information from multiple national population-based registries in Sweden. Results: Treatment with antidepressants is more common in patients with malignant glioma (27%), compared to controls (16%), P < .001. Treatment with antidepressants after surgery for glioma was significantly associated with poorer survival. These effects were observed both for selective serotonin reuptake inhibitors (SSRIs) and non-SSRIs. In grade 4 glioma, SSRI treatment was associated with a hazard ratio (HR) of 3.32 (95% CI 2.69-4.10, P < .001), and non-SSRI treatment a HR of 3.54 (95% CI 2.52-4.99, P < .001), compared to glioma patients without antidepressants. In grade 2-3 glioma, the HR for SSRI treatment was 3.26 (95% CI 2.19-4.85, P < .001), and for non-SSRI treatment was 7.71 (95% CI 4.22-14.12, P < .001). Conclusions: Our results demonstrate a negative association between antidepressant medication and survival in glioma. Further research will be needed to clarify causation.

Direct letters to relatives at risk of hereditary cancer-study protocol for a multi-center randomized controlled trial of healthcare-assisted versus family-mediated risk disclosure at Swedish cancer genetics clinics (DIRECT-study).

BACKGROUND: The results of germline genetic testing for hereditary cancer are of importance not only to the patients under investigation but also to their genetic at-risk relatives. Standard care is to encourage the proband (first family member under investigation) to pass on this risk information to the relatives. Previous research suggests that with family-mediated disclosure, only about a third of at-risk relatives contact health care to receive genetic counselling. In some studies, complementing family-mediated risk disclosure with healthcare-assisted risk disclosure almost doubles the uptake of genetic counselling in at-risk relatives. In this study, we evaluate healthcare-assisted direct letters to relatives at risk of hereditary cancer syndromes in a randomized controlled trial. METHODS: Probands are recruited from Swedish outpatient cancer genetics clinics to this two-arm randomized controlled trial. The study recruits probands with either a pathogenic variant in a cancer susceptibility gene (BRCA1, BRCA2, PALB2, MLH1, MSH2, MSH6, PMS2) or probands with familial breast and colorectal cancer based on clinical and pedigree criteria. In both arms, probands receive standard care, i.e., are encouraged and supported to pass on information to relatives. In the intervention arm, the proband is also offered to have direct letters sent to the at-risk relatives. The primary outcome measure is the proportion of at-risk relatives contacting a Swedish cancer genetics clinic within 12 months of the proband receiving the test results. DISCUSSION: This paper describes the protocol of a randomized controlled clinical trial evaluating a healthcare-assisted approach to risk disclosure by offering the probands to send direct letters to their at-risk relatives. The results of this study should be informative in the future development of risk disclosure practices in cancer genetics clinics. TRIAL REGISTRATION: ClinicalTrials.gov. Identifier NCT04197856 (pre-trial registration on December 13, 2019). Also registered at the website "RCC Cancerstudier i Sverige" as study #86719.

Public support for healthcare-mediated disclosure of hereditary cancer risk information: Results from a population-based survey in Sweden.

BACKGROUND: Targeted surveillance of at-risk individuals in families with increased risk of hereditary cancer is an effective prevention strategy if relatives are identified, informed and enrolled in screening programs. Despite the potential benefits, many eligible at-risk relatives remain uninformed of their cancer risk. This study describes the general public's opinion on disclosure of hereditary colorectal cancer (CRC) risk information, as well as preferences on the source and the mode of information. METHODS: A random sample of the general public was assessed through a Swedish citizen web-panel. Respondents were presented with scenarios of being an at-risk relative in a family that had an estimated increased hereditary risk of CRC; either 10% (moderate) or 70% (high) lifetime risk. A colonoscopy was presented as a preventive measure. Results were analysed to identify significant differences between groups using the Pearson's chi-square (χ2) test. RESULTS: Of 1800 invited participants, 977 completed the survey (54%). In the moderate and high-risk scenarios, 89.2 and 90.6% respectively, would like to receive information about a potential hereditary risk of CRC (χ2, p = .755). The desire to be informed was higher among women (91.5%) than men (87.0%, χ2, p = .044). No significant differences were found when comparing different age groups, educational levels, place of residence and having children or not. The preferred source of risk information was a healthcare professional in both moderate and high-risk scenarios (80.1 and 75.5%). However, 18.1 and 20.1% respectively would prefer to be informed by a family member. Assuming that healthcare professionals disclosed the information, the favoured mode of information was letter and phone (38.4 and 33.2%). CONCLUSIONS: In this study a majority of respondents wanted to be informed about a potential hereditary risk of CRC and preferred healthcare professionals to communicate this information. The two presented levels of CRC lifetime risk did not significantly affect the interest in being informed. Our data offer insights into the needs and preferences of the Swedish population, providing a rationale for developing complementary healthcare-assisted communication pathways to realise the full potential of targeted prevention of hereditary CRC.

Travel time to care does not affect survival for patients with colorectal cancer in northern Sweden: A data linkage study from the Risk North database.

INTRODUCTION: Numerous prior studies, even from countries with free access to care, have associated long travel time to care with poor survival in patients with colorectal cancer. METHODS: This is a data-linkage study of all 3718 patients with colorectal cancer, diagnosed between 2007 and 2013 in Northern Sweden, one of the most sparsely populated areas in Europe. Travel time to nearest hospital was calculated based on GPS coordinates and multivariable Cox regression was used to analyse possible associations between travel time and cause-specific survival. RESULTS: No association between travel time and survival was observed, either in univariable analysis (colon HR 1.00 [95% CI 0.998-1.003]; rectal HR 0.998; [95% CI 0.995-1.002]) or in multivariable Cox regression analysis (colon HR 0.999 [95% CI 0.997-1.002]; rectal HR 0.997 [95% CI 0.992-1.002]). CONCLUSIONS: In contrast to most other studies, no association between travel time and colorectal cancer survival was found; despite that longer travel time was associated with known risk factors for poorer outcome. In the Swedish health care setting, travel time does not appear to represent a barrier to care or to negatively influence outcomes.

Effectiveness of population-based service screening with mammography for women ages 40 to 49 years with a high or low risk of breast cancer: socioeconomic status, parity, and age at birth of first child.

BACKGROUND: Invitation to mammography screening of women aged 40 to 49 years is a matter of debate in many countries and a cost-effective alternative in countries without screening among women aged 40 to 49 years could be inviting those at higher risk. The relative effectiveness of mammography screening was estimated for subgroups based on the breast cancer risk factors parity, age at time of birth of first child, and socioeconomic status (SES). METHODS: The SCReening of Young Women (SCRY) database consists of all women aged 40 to 49 years in Sweden between 1986 and 2005 and was split into a study and control group. The study group consisted of women residing in areas in which women aged 40 to 49 years were invited to screening and the control group of women in areas in which women aged 40 to 49 years were not invited to screening. Rate ratio (RR) estimates were calculated for 2 exposures: invitation and attendance. RESULTS: There were striking similarities noted in the RR pattern for women invited to and attending screening and no statistically significant difference or trend in the RR was noted by risk group. The RR estimates increased by increasing parity for parity of 0 to 2 and ranged from 0.55 (95% confidence interval [95% CI], 0.38-0.79) to 0.79 (95% CI, 0.65-0.95) for attending women. The RR for women with high SES was lower than that for women with low SES (RR, 0.72 [95% CI, 0.60-0.86] and RR, 0.79 [95% CI, 0.63-0.99], respectively). For women aged 20 to 24 years at the time of the birth of their first child, the RR was 0.73 (95% CI, 0.58-0.91) and estimates for other ages were similar. CONCLUSIONS: There was no statistically significant difference noted in the relative effectiveness of mammography screening by parity, age at the time of birth of the first child, or SES.

Overdiagnosis in the population-based service screening programme with mammography for women aged 40 to 49 years in Sweden.

OBJECTIVES: To estimate the level of overdiagnosis of all breast cancers and of invasive breast cancers in women aged 40-49 invited to the subsequent screening rounds in the Swedish service-screening programme 1986-2005. METHODS: To estimate the level of overdiagnosis in subsequent screening, the rate ratios (RR) of the breast cancer incidence in the study group (women in areas with screening in ages 40-49) and the control group (women in areas with no screening in ages 40-49) were calculated for all breast cancers and for invasive breast cancers. The RR estimates were adjusted for the prescreening difference in incidence between study and control group and for lead time. RESULTS: The prescreening incidence rate ratio was estimated at 0.92 (95% confidence interval [CI]: 0.88-0.97). The number of breast cancer cases and person-years were 6047 and 3.8 million, and 7790 and 5.2 million, in the study group and control group respectively during the study period. The RR estimate for all cancers was 1.01 (95% CI: 0.94-1.08) when adjusted for prescreening difference and a lead time of 1.2 years. The corresponding estimate for invasive breast cancers was 0.95 (95% CI: 0.88-1.02). CONCLUSIONS: We found no significant overdiagnosis for women aged 40-49 in the Swedish service screening programme with mammography.

Effectiveness of population-based service screening with mammography for women ages 40 to 49 years: evaluation of the Swedish Mammography Screening in Young Women (SCRY) cohort.

BACKGROUND: The effectiveness of mammography screening for women ages 40 to 49 years still is questioned, and few studies of the effectiveness of service screening for this age group have been conducted. METHODS: Breast cancer mortality was compared between women who were invited to service screening at ages 40 to 49 years (study group) and women in the same age group who were not invited during 1986 to 2005 (control group). Together, these women comprise the Mammography Screening of Young Women (SCRY) cohort, which includes all Swedish counties. A prescreening period was defined to facilitate a comparison of mortality in the absence of screening. The outcome measure was refined mortality, ie, breast cancer death for women who were diagnosed during follow-up at ages 40 to 49 years. Relative risks (RRs) with 95% confidence intervals (CIs) were estimated. RESULTS: There was no significant difference in breast cancer mortality during the prescreening period. During the study period, there were 803 breast cancer deaths in the study group (7.3 million person-years) and 1238 breast cancer deaths in the control group (8.8 million person-years). The average follow-up was 16 years. The estimated RR for women who were invited to screening was 0.74 (95% CI, 0.66-0.83), and the RR for women who attended screening was 0.71 (95% CI, 0.62-0.80). CONCLUSIONS: In this comprehensive study, mammography screening for women ages 40 to 49 years was efficient for reducing breast cancer mortality.