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Background: Epidemiological evidence indicates that individuals with type 2 diabetes are at an increased risk of cancer. Elevated glucose levels, below the diagnostic threshold for diabetes, have also been suggested to be associated with increased cancer risks. Methods: We investigated possible associations between glucose levels and the risk of breast, endometrial, and ovarian cancer in a cohort of more than 230,000 women, for which information on outcome and potential confounders was obtained by record linkage to population-based registers. Results: Diabetes was associated with an increased risk of postmenopausal breast cancer (HR = 1.22, 95% CI 1.04-1.43). An indication of a slightly elevated breast cancer risk was also found in postmenopausal women with impaired glucose metabolism (HR = 1.11, 95% CI 0.96-1.28). Diabetes (HR = 1.46, 95% CI 1.09-1.96) and impaired glucose metabolism (HR = 1.41, 95% CI 1.08-1.85) were associated with an increased risk of endometrial cancer. No associations were found between glucose levels and ovarian cancer risk. Following adjustment for BMI, estimates were attenuated for endometrial cancer, while point estimates for breast and ovarian cancer remained essentially unchanged. Conclusions: Our results indicate that glucose levels below the diagnostic threshold for diabetes modify the risk not only of endometrial cancer but possibly also of postmenopausal breast cancer.

Improved cancer survival poses important questions about future life conditions of the survivor. We examined the possible influence of a breast cancer diagnosis on subsequent working and marital status, sickness absence and income. We conducted a matched cohort study including 4,761 women 40-59 years of age and registered with primary breast cancer in a Swedish population-based clinical register during 1993-2003, and 2,3805 women without breast cancer. Information on socioeconomic standing was obtained from a social database 1 year prior and 3 and 5 years following the diagnosis. In Conditional Poisson Regression models, risk ratios (RRs) and 95% confidence intervals (CIs) were estimated to assess the impact of a breast cancer diagnosis. Three years after diagnosis, women who had had breast cancer more often had received sickness benefits (RR = 1.49, 95% CI 1.40-1.58) or disability pension (RR = 1.47, 95% CI 1.37-1.58) than had women without breast cancer. We found no effect on income (RR = 0.99), welfare payments (RR = 0.98), or marital status (RR = 1.02). A higher use of sickness benefits and disability pension was evident in all stages of the disease, although the difference in use of sickness benefits decreased after 5 years, whereas the difference in disability pension increased. For woman with early stage breast cancer, the sickness absence was higher following diagnosis among those with low education, who had undergone mastectomy, and had received chemo- or hormonal therapy. Neither tumour size nor presence of lymph nodes metastasis was associated with sickness absence after adjustment for treatment. Even in early stage breast cancer, a diagnosis negatively influences working capacity both 3 and 5 years after diagnosis, and it seems that the type of treatment received had the largest impact. A greater focus needs to be put on rehabilitation of breast cancer patients, work-place adaptations and research on long-term sequelae of treatment.

Impaired glucose metabolism has been linked with increased cancer risk, but the association between serum glucose and cancer risk remains unclear. We used repeated measurements of glucose and fructosamine to get more insight into the association between the glucose metabolism and risk of cancer. We selected 11,998 persons (>20 years old) with four prospectively collected serum glucose and fructosamine measurements from the Apolipoprotein Mortality Risk (AMORIS) study. Multivariate Cox proportional hazards regression was used to assess standardized log of overall mean glucose and fructosamine in relation to cancer risk. Similar analyses were performed for tertiles of glucose and fructosamine and for different types of cancer. A positive trend was observed between standardized log overall mean glucose and overall cancer risk (HR= 1.08; 95% CI: 1.02-1.14). Including standardized log fructosamine in the model resulted in a stronger association between glucose and cancer risk and aninverse association between fructosamine and cancer risk (HR = 1.17; 95% CI: 1.08-1.26 and HR: 0.89; 95% CI: 0.82-0.96, respectively). Cancer risks were highest among those in the highest tertile of glucose and lowest tertile of fructosamine. Similar findings were observed for prostate, lung, and colorectal cancer while none observed for breast cancer. The contrasting effect between glucose, fructosamine, and cancer risk suggests the existence of distinct groups among those with impaired glucose metabolism, resulting in different cancer risks based on individual metabolic profiles. Further studies are needed to clarify whether glucose is a proxy of other lifestyle-related or metabolic factors.

Adherence to long-term pharmacological treatment for chronic conditions is often less than optimal. Till date, a limited number of population-based studies have assessed adherence to adjuvant hormonal therapy in breast cancer, a therapy with proven benefits in terms of reductions of recurrence and mortality. We aimed to examine rates of adherence and early discontinuation in Sweden where prescribed medications are subsidized for all residents and made available at reduced out-of-pocket costs. Individual-level data were obtained from Regional Clinical Quality Breast Cancer Registers, the Swedish Prescribed Drug Register, and several other population-based registers. Multivariate logistic regression was used to analyze factors associated with adherence to prescribed medication for a period of 3 years. Between January 1 and December 31, 2005, 1,741 patients in central Sweden were identified with estrogen receptor positive breast cancer, and at least one prescription dispensation of either tamoxifen or an aromatase inhibitor. Of these women, 1,193 (69%) were fully adherent to therapy for 3 years (medication possession ratio of 80% or higher and a maximum of 180 days between refills). During the 3-year follow-up, 215 women (12%) had prematurely discontinued therapy. Adherence was positively associated with younger age, large tumor size, being married, and being born in the Nordic countries, while no clear association was observed with education or income. During the 3 years of follow-up, 31% of women were non-adherent to therapy. Further efforts must be undertaken to promote adherence over the entire recommended treatment period.

To investigate associations between comorbidity burden, management, and mortality in women with breast cancer. A total of 42,646 women diagnosed with breast cancer between 1992 and 2008 were identified in two Clinical Quality Registers in Central Sweden. Breast cancer-specific, conditional breast cancer, competing-cause and all-cause mortality were estimated in relation to comorbidity burden assessed by the Charlson comorbidity index. All analyses were stratified by stage at diagnosis using competing risk analyses, and all-cause mortality was estimated as a function of follow-up time. Following adjustment for age and calendar period, breast conserving surgery was significantly less likely to be offered to women with severe comorbidity (OR 0.63; 95 % CI 0.58–0.69). Similarly, the proportion treated with radiotherapy, tamoxifen, or chemotherapy was lower in women with severe compared to those with no comorbidity. In women with early stage disease, breast cancer-specific mortality was higher among patients with severe comorbidity (sHR 1.47; 95 % CI 1.11–1.94). In all stages of breast cancer, conditional breast cancer and competing-cause mortality were elevated in women with severe comorbidity. For all stages, the relative risk of all-cause mortality between women with severe versus no comorbidity varied by time since diagnosis, and was most pronounced at early follow-up. Comorbidity affects treatment decisions and mortality. In women with early stage breast cancer, severe comorbidity was associated not only with conditional breast cancer, competing-cause and all-cause mortality, but also breast cancer-specific mortality. The observed differences in breast cancer-specific mortality may be due to less extensive treatment, impaired tumor defense and differences in general health status and lifestyle factors.

Background The aim of the study was to identify demographic and socioeconomic characteristics of participants and non-participants in a Swedish population-based case-control study on brain tumours and to analyse the association between socioeconomic factors and glioma and meningioma risk. Methods Record linkage was made to an official register to gather information on socioeconomic status, income, education and demography for all participating and non-participating cases and controls. Results 494 glioma cases, 321 meningioma cases and 955 controls were eligible and 74%, 85% and 70%, respectively, participated. Working status and income level were positively associated with participation among cases and controls. Among both cases and controls, being married, and having a high education were also associated with participation. Having a family income level in the highest quartile was associated with an increased glioma risk (OR 1.5, 95% CI 1.1 to 2.1). This risk increase diminished when only participating individuals were included in the analysis. Socioeconomic factors were not associated with meningioma risk. Conclusions Non-participation, related to socioeconomic factors, is a potential source of bias in case-control studies that should be acknowledged; however, the effect was not large in the present study due to the fact that the level of participation was comparable between cases and controls and participation was similarly influenced by socioeconomic factors among cases and controls. The association between a high income level and an increased glioma risk and possible underlying factors needs to be explored further.

Studies from Western countries have found evidence of a recent decline in breast cancer incidence rates in postmenopausal women, findings which have been hypothesized to reflect a reduced use of hormonal replacement therapy (HRT). We examined breast cancer incidence trends in Sweden between 1997 and 2007, a period characterized by a drop in the use of HRT. Incidence trends were assessed using data from three population-based Regional Clinical Registries on breast cancer covering 2/3 of the Swedish population. Information on HRT sales was obtained from national pharmacy data. The prevalence of HRT use in age group 50-59 years decreased from a peak of 36% in 1999 to 27% in 2002 and further to 9% in 2007. Incidence rates of breast cancer in women 50 years and older increased between 1997 and 2003. A significant decrease in incidence between 2003 and 2007 was confined to women 50-59 years of age, the group in which the prevalence of HRT use has been highest and the decrease in use most pronounced. As opposed to the immediate effects reported from the United States and other regions, there was a time lag between the drop in HRT use and clear reductions in breast cancer incidence. This may reflect between country differences with regard to types of HRT used, and the rate, magnitude and pattern of change in use. The present findings give further support to the notion that HRT use is a driver of breast cancer incidence trends on the population level.

Aims: This study analyses the applicability of some of the registers used within the healthcare system for estimations of disease prevalence. The study focuses on the diagnoses of asthma, diabetes mellitus, chronic bronchitis/emphysema, hypertensive disease, and cerebrovascular disease. Methods: The study population comprised all inhabitants (n=20,037) in the municipality of Tierp on 31 December 1996. Diagnostic information was collected from primary healthcare and occupational healthcare in the municipality of Tierp and from inpatient and outpatient units at the hospitals in Uppsala County. The proportion of registered patients in the different registers was calculated in relation to the total number of patients who had been registered during 1996 with the selected diagnoses. Results: In the primary healthcare register, between 67% (cerebrovascular disease) and 85% (asthma) of all patients with selected diagnoses could be identified. A search on the inpatient care register (Hospital Discharge Register) led to the identification of between 8% (hypertensive disease) and 53% (cerebrovascular disease) of the patients. Conclusions: For all of the examined diagnoses, most patients could be identified in the primary healthcare register. Register data from both primary healthcare and inpatient and outpatient care at hospital are needed to make reasonable estimates of prevalence.

Every year approximately 1200 people in Sweden are diagnosed with a brain tumor. The two main histological types of brain tumors, gliomas and meningiomas, differ in terms of their localization, histology, prognosis, and probably etiology. Exposure to ionizing radiation and a few rare genetic syndromes are the only unequivocally established risk factors.The overall aim of this thesis was to look at some specific factors that potentially could be associated with glioma and meningioma risk, and to characterize and compare demographic and socioeconomic factors among participants and non-participants in a case-control study of brain tumors. Data from an international population-based case-control study of brain tumors formed the base for the papers included in the thesis. In papers I and IV only Swedish participants were included. Papers II and III included participants from Denmark, Finland, Norway, Sweden, and England.We found an increased risk of meningioma associated with use of hormone replacement therapy. We found no association between use of oral contraceptives and meningioma risk, but results indicated an increased risk associated with use of other hormonal contraceptives. No associations were found between use of exogenous female sex hormones and glioma. Increasing number of pregnancies leading to a live birth was associated with an increased meningioma risk among women < 50 years of age, but not among older women. Ever having been pregnant was associated with a decreased glioma risk. Among parous women longer duration of breastfeeding and older age when giving birth for the fist time was associated with an increased glioma risk.Allergic conditions (asthma, eczema, hay fever, other allergy) were associated with a reduced glioma risk, OR=0.70 (95% CI: 0.61-0.80), which is in accordance with previously published studies. We showed that the inverse association was primarily related to current allergic condition and was not influenced by anti-allergy treatment. Allergic conditions were not associated with meningioma risk, except for a decreased risk associated with eczema.Records were linked to registries at Statistics Sweden to gather information on socioeconomic status, income, and education, for all participating and non-participating cases and controls in the Swedish part of the study. Working status and income level were positively associated with participation among both cases and controls. A high income level was associated with a slightly increased risk of glioma, but not related to meningioma risk.Conclusions: Our findings imply that female sex hormones influence the occurrence of meningioma and glioma. The results also indicate that immunological factors are of importance for glioma tumorigenesis. Non-participation related to socioeconomic factors should always be acknowledged as a potential source of selection bias, but the influence was not large in our study due to the fact that the level of participation was comparable between cases and controls and participation was similarly influenced by socioeconomic factors among cases and controls.

Aims: This study analyses the applicability of some of the registers used within the healthcare system for estimations of disease prevalence .The study focuses on the diagnoses of asthma, diabetes mellitus, chronic bronchitis/emphysema, hypertensive disease, and cerebrovascular disease. Methods: The study population comprised all inhabitants ( n=20,037) in the municipality of Tierp on 31 December 1996. Diagnostic information was collected from primary healthcare and occupational healthcare in the municipality of Tierp and from inpatient and outpatient units at the hospitals in Uppsala County. The proportion of registered patients in the different registers was calculated in relation to the total number of patients who had been registered during 1996 with the selected diagnoses . Results: In the primary healthcare register, between 67% ( cerebrovascular disease) and 85% ( asthma) of all patients with selected diagnoses could be identified. A search on the inpatient care register ( Hospital Discharge Register) led to the identification of between 8% ( hypertensive disease) and 53% ( cerebrovascular disease) of the patients. Conclusions: For all of the examined diagnoses, most patients could be identified in the primary healthcare register. Register data from both primary healthcare and inpatient and outpatient care at hospital are needed to make reasonable estimates of prevalence.