| 1. |
- Abe, O, et al.
(author)
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Effects of chemotherapy and hormonal therapy for early breast cancer on recurrence and 15-year survival: an overview of the randomised trials
- 2005
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In: The Lancet. - 1474-547X. ; 365:9472, s. 1687-1717
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Journal article (peer-reviewed)abstract
- Background Quinquennial overviews (1985-2000) of the randomised trials in early breast cancer have assessed the 5-year and 10-year effects of various systemic adjuvant therapies on breast cancer recurrence and survival. Here, we report the 10-year and 15-year effects. Methods Collaborative meta-analyses were undertaken of 194 unconfounded randomised trials of adjuvant chemotherapy or hormonal therapy that began by 1995. Many trials involved CMF (cyclophosphamide, methotrexate, fluorouracil), anthracycline-based combinations such as FAC (fluorouracil, doxombicin, cyclophosphamide) or FEC (fluorouracil, epirubicin, cyclophosphamide), tamoxifen, or ovarian suppression: none involved taxanes, trastuzumab, raloxifene, or modem aromatase inhibitors. Findings Allocation to about 6 months of anthracycline-based polychemotherapy (eg, with FAC or FEC) reduces the annual breast cancer death rate by about 38% (SE 5) for women younger than 50 years of age when diagnosed and by about 20% (SE 4) for those of age 50-69 years when diagnosed, largely irrespective of the use of tamoxifen and of oestrogen receptor (ER) status, nodal status, or other tumour characteristics. Such regimens are significantly (2p=0 . 0001 for recurrence, 2p<0 . 00001 for breast cancer mortality) more effective than CMF chemotherapy. Few women of age 70 years or older entered these chemotherapy trials. For ER-positive disease only, allocation to about 5 years of adjuvant tamoxifen reduces the annual breast cancer death rate by 31% (SE 3), largely irrespective of the use of chemotherapy and of age (<50, 50-69, &GE; 70 years), progesterone receptor status, or other tumour characteristics. 5 years is significantly (2p<0 . 00001 for recurrence, 2p=0 . 01 for breast cancer mortality) more effective than just 1-2 years of tamoxifen. For ER-positive tumours, the annual breast cancer mortality rates are similar during years 0-4 and 5-14, as are the proportional reductions in them by 5 years of tamoxifen, so the cumulative reduction in mortality is more than twice as big at 15 years as at 5 years after diagnosis. These results combine six meta-analyses: anthracycline-based versus no chemotherapy (8000 women); CMF-based versus no chemotherapy (14 000); anthracycline-based versus CMF-based chemotherapy (14 000); about 5 years of tamoxifen versus none (15 000); about 1-2 years of tamoxifen versus none (33 000); and about 5 years versus 1-2 years of tamoxifen (18 000). Finally, allocation to ovarian ablation or suppression (8000 women) also significantly reduces breast cancer mortality, but appears to do so only in the absence of other systemic treatments. For middle-aged women with ER-positive disease (the commonest type of breast cancer), the breast cancer mortality rate throughout the next 15 years would be approximately halved by 6 months of anthracycline-based chemotherapy (with a combination such as FAC or FEC) followed by 5 years of adjuvant tamoxifen. For, if mortality reductions of 38% (age <50 years) and 20% (age 50-69 years) from such chemotherapy were followed by a further reduction of 31% from tamoxifen in the risks that remain, the final mortality reductions would be 57% and 45%, respectively (and, the trial results could well have been somewhat stronger if there had been full compliance with the allocated treatments). Overall survival would be comparably improved, since these treatments have relatively small effects on mortality from the aggregate of all other causes. Interpretation Some of the widely practicable adjuvant drug treatments that were being tested in the 1980s, which substantially reduced 5-year recurrence rates (but had somewhat less effect on 5-year mortality rates), also substantially reduce 15-year mortality rates. Further improvements in long-term survival could well be available from newer drugs, or better use of older drugs.
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| 2. |
- Abril, Jazmine, et al.
(author)
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Associations between pregnancy-related factors and birth characteristics with risk of rare uterine cancer subtypes : a Nordic population-based case-control study
- 2024
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In: Cancer Causes and Control. - : Springer. - 0957-5243 .- 1573-7225. ; 35:5, s. 741-747
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Journal article (peer-reviewed)abstract
- Purpose: Uterine sarcomas are a rare group of uterine malignancies. Due to the low incidence and changes in uterine sarcoma classification, risk factors are not well characterized. Our objective was to evaluate risk factors for uterine sarcoma and compare risk factors between uterine sarcoma, malignant mixed Mullerian tumors (MMMTs), and type I endometrial carcinomas.Methods: This nested case-control study utilized linked data from population-based medical birth and cancer registries in Denmark, Finland, Norway, and Sweden. Up to 10 controls were matched on country and birth year for each uterine cancer case. Using multivariable adjusted multinomial logistic regression, estimates of the associations between pregnancy-related factors and risk of uterine sarcoma, MMMTs, and type I endometrial carcinomas were determined.Results: Having a very-low-birth-weight infant (< 1500 vs. 2500-3999 g: OR [95% CI] 2.83 [1.61-4.96]) was associated with an increased risk of uterine sarcoma. Whereas, having a more recent pregnancy was associated with reduced risks of MMMT (< 10 vs. >= 30 years: 0.66 [0.20-2.23]) and type 1 endometrial carcinomas (0.35 [0.30-0.41]) but not uterine sarcomas (1.33 [0.90-1.98], p-heterogeneity < 0.01).Conclusion: Our study provides evidence that risk factors for uterine sarcoma and MMMT, previously grouped with uterine sarcomas, vary substantially. Additionally, MMMT and type I endometrial carcinomas are more similar than uterine sarcoma in that pregnancy complications like gestational hypertension and preeclampsia were associated with reduced risks of both but not uterine sarcoma, suggesting different etiologies.
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| 3. |
- Amsberg, Susanne, et al.
(author)
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Acceptance and commitment therapy (ACT) for adult type 1 diabetes management : study protocol for a randomised controlled trial
- 2018
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In: BMJ Open. - : BMJ. - 2044-6055. ; 8:11
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Journal article (peer-reviewed)abstract
- INTRODUCTION: Integrating diabetes self-management into daily life involves a range of complex challenges for affected individuals. Environmental, social, behavioural and emotional psychological factors influence the lives of those with diabetes. The aim of this study is to evaluate the impact of a stress management group intervention based on acceptance and commitment therapy (ACT) among adults living with poorly controlled type 1 diabetes.METHODS AND ANALYSIS: This study will use a randomised controlled trial design evaluating treatment as usual (TAU) and ACT versus TAU. The stress management group intervention will be based on ACT and comprises a programme divided into seven 2-hour sessions conducted over 14 weeks. A total of 70 patients who meet inclusion criteria will be recruited over a 2-year period with follow-up after 1, 2 and 5 years.The primary outcome measure will be HbA1c. The secondary outcome measures will be the Depression Anxiety Stress Scales, the Swedish version of the Hypoglycemia Fear Survey, the Swedish version of the Problem Areas in Diabetes Scale, The Summary of Self-Care Activities, Acceptance Action Diabetes Questionnaire, Swedish Acceptance and Action Questionnaire and the Manchester Short Assessment of Quality of Life. The questionnaires will be administered via the internet at baseline, after sessions 4 (study week 7) and 7 (study week 14), and 6, 12 and 24 months later, then finally after 5 years. HbA1c will be measured at the same time points.Assessment of intervention effect will be performed through the analysis of covariance. An intention-to-treat approach will be used. Mixed-model repeated measures will be applied to explore effect of intervention across all time points.ETHICS AND DISSEMINATION: The study has received ethical approval (Dnr: 2016/14-31/1). The study findings will be disseminated through peer-reviewed publications, conferences and reports to key stakeholders.TRIAL REGISTRATION NUMBER: NCT02914496; Pre-results.
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| 4. |
- Bjørge, Tone, et al.
(author)
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Reproductive history and risk of colorectal adenocarcinoma in parous women : a Nordic population-based case-control study
- 2016
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In: British Journal of Cancer. - : Springer Science and Business Media LLC. - 0007-0920 .- 1532-1827. ; 115:11, s. 1416-1420
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Journal article (peer-reviewed)abstract
- Background: Data are conflicting regarding the role of endogenous sex hormones in colorectal carcinogenesis. In this large population-based study, we pooled data from birth and cancer registries in four Nordic countries, to evaluate the risk of colorectal adenocarcinoma in relation to women's reproductive history. Methods: We conducted a population-based case-control study among women registered in Nordic birth registries. The study included colorectal adenocarcinoma cases diagnosed in Denmark, Finland, Norway, and Sweden during 1967-2013 and up to 10 matched controls per case, in total 22 185 cases and 220 246 controls. Odds ratios (ORs) with 95% confidence intervals (95% CIs) were derived from conditional logistic regression models. We had limited information available on possible confounders. Results: We found no evidence for associations between colorectal adenocarcinoma and parity, age at first and last birth, and time since first and last birth. The risk estimates were also close to unity for specific cancer subsites (proximal and distal colon and rectum). As well, when the analyses were stratified on menopausal status, parity, and mother's year of birth, no indication of associations was found. Conclusions: In this large, Nordic population-based study, no evidence for associations was found between women's reproductive history and colorectal adenocarcinoma in parous women.
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| 5. |
- Daltveit, Dagrun Slettebo, et al.
(author)
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Cancer risk in the siblings of individuals with major birth defects : a large Nordic population-based case-control study
- 2023
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In: International Journal of Epidemiology. - : Oxford University Press. - 0300-5771 .- 1464-3685. ; 52:6, s. 1826-1835
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Journal article (peer-reviewed)abstract
- Background: Individuals with major birth defects are at increased risk of developing cancer, indicating a common aetiology. However, whether the siblings of individuals with birth defects are also at an increased risk of cancer is unclear.Methods: We used nationwide health registries in four Nordic countries and conducted a nested case-control study. We included 40 538 cancer cases (aged 0-46 years) and 481 945 population controls (matched by birth year and country), born between 1967 and 2014. The relative risk of cancer among individuals whose siblings had birth defects was computed with odds ratios (OR) and 95% confidence intervals (CIs), using logistic regression models.Results: In the total study population (aged 0-46 years), we observed no overall difference in cancer risk between individuals whose siblings had birth defects and those who had unaffected siblings (OR 1.02; 95% CI 0.97-1.08); however, the risk of lymphoid and haematopoietic malignancies was elevated (1.16; 1.05-1.28). The overall risk of childhood cancer (0-19 years) was increased for siblings of individuals who had birth defects (1.09; 1.00-1.19), which was mainly driven by lymphoma (1.35; 1.09-1.66), neuroblastoma (1.51; 1.11-2.05) and renal carcinoma (5.03; 1.73-14.6). The risk of cancer also increased with the number of siblings with birth defects (P-trend = 0.008).Conclusion: Overall risk of cancer among individuals (aged 0-46 years) whose siblings had birth defects was not elevated, but the risk of childhood cancer (ages 0-19 years) was increased. Our novel findings are consistent with the common aetiologies of birth defects and cancer, such as shared genetic predisposition and environmental factors.
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| 6. |
- Daltveit, Dagrun Slettebo, et al.
(author)
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Sex differences in childhood cancer risk among children with major birth defects : a Nordic population-based nested case-control study
- 2023
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In: International Journal of Epidemiology. - : Oxford University Press. - 0300-5771 .- 1464-3685. ; 52:2, s. 450-465
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Journal article (peer-reviewed)abstract
- Background Childhood cancer is more common among children with birth defects, suggesting a common aetiology. Whether this association differs by sex is unclear. Methods We performed a population-based nested case-control study using nationwide health registries in four Nordic countries. We included 21 898 cancer cases (0-19 years) and 218 980 matched population controls, born 1967-2014. Associations between childhood cancer and major birth defects were calculated as odds ratios (ORs) with 95% confidence intervals (CIs) using logistic regression models. Effect modification was evaluated using a counterfactual framework to estimate confidence intervals and P-values for the natural indirect effects. Results Birth defects were present for 5.1% (1117/21 898) of childhood cancer cases and 2.2% (4873/218 980) of controls; OR of cancer was higher for chromosomal (OR = 10, 95% CI = 8.6-12) than for non-chromosomal defects (OR = 1.9, 95% CI = 1.8-2.1), strongest between genetic syndromes/microdeletion and renal tumours, Down syndrome and leukaemia, and nervous system defects and central nervous system tumours. The association between birth defects and cancer was stronger among females (OR = 2.8, 95% CI = 2.6-3.1) than males (OR = 2.1, 95% CI = 1.9-2.2, P-interaction <0.001). Male sex was an independent risk factor for childhood cancer, but very little of the overall association between sex and childhood cancer was mediated through birth defects (4.8%, P-NIE <0.001), although more at younger ages (10% below years and 28% below 1 year). Conclusions The birth defect-cancer associations were generally stronger among females than males. Birth defects did not act as a strong mediator for the modest differences in childhood cancer risk by sex, suggesting that other biological pathways are involved.
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| 7. |
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| 8. |
- Kitahara, Cari M., et al.
(author)
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Maternal health, in-utero, and perinatal exposures and risk of thyroid cancer in offspring : a Nordic population-based nested case-control study
- 2021
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In: The Lancet Diabetes and Endocrinology. - : Elsevier. - 2213-8587 .- 2213-8595. ; 9:2, s. 94-105
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Journal article (peer-reviewed)abstract
- Background Thyroid cancer tends to be diagnosed at a younger age (median age 51 years) compared with most other malignancies (such as breast cancer [62 years] or lung cancer [71 years]). The incidence of thyroid cancer is higher in women than men diagnosed from early adolescence. However, few in-utero and early life risk exposures associated with increased risk of thyroid cancer have been identified. Methods In this population-based nested case-control study we used registry data from four Nordic countries to assess thyroid cancer risk in offspring in relation to maternal medical history, pregnancy complications, and birth characteristics. Patient with thyroid cancer (cases) were individuals born and subsequently diagnosed with first primary thyroid cancer from 1973 to 2013 in Denmark, 1987 to 2014 in Finland, 1967 to 2015 in Norway, or 1973 to 2014 in Sweden. Each case was matched with up to ten individuals without thyroid cancer (controls) based on birth year, sex, country, and county of birth. Cases and matched controls with a previous diagnosis of any cancer, other than non-melanoma skin cancer, at the time of thyroid cancer diagnosis were excluded. Cases and matched controls had to reside in the country of birth at the time of thyroid cancer diagnosis. Conditional logistic regression models were used to calculate odds ratios (ORs) with 95% CIs. Findings Of the 2437 cases, 1967 (81.4%) had papillary carcinomas, 1880 (77.1%) were women, and 1384 (56.7%) were diagnosed before age 30 years (range 0-48). Higher birth weight (OR per kg 1.14 [95% CI 1.05-1.23]) and congenital hypothyroidism (4.55 [1.58-13.08]); maternal diabetes before pregnancy (OR 1.69 [0.98-2.93]) and postpartum haemorrhage (OR 1.28 [1.06-1.55]); and (from registry data in Denmark) maternal hypothyroidism (18.12 [10.52-31.20]), hyperthyroidism (11.91 [6.77-20.94]), goiter (67.36 [39.89-113.76]), and benign thyroid neoplasms (22.50 [6.93-73.06]) were each associated with an increased risk of thyroid cancer in offspring. Interpretation In-utero exposures, particularly those related to maternal thyroid disorders, might have a long-term influence on thyroid cancer risk in offspring.
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| 9. |
- Kitahara, Cari M., et al.
(author)
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Maternal Health, Pregnancy and Offspring Factors, and Maternal Thyroid Cancer Risk : A Nordic Population-Based Registry Study
- 2023
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In: American Journal of Epidemiology. - : Oxford University Press. - 0002-9262 .- 1476-6256. ; 192:1, s. 70-83
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Journal article (peer-reviewed)abstract
- Thyroid cancer incidence is higher in women than men, especially during the reproductive years, for reasons that remain poorly understood. Using population-based registry data from 4 Nordic countries through 2015, we examined associations of perinatal characteristics with risk of maternal thyroid cancer. Cases were women diagnosed with thyroid cancer >= 2 years after last birth (n = 7,425, 83% papillary). Cases were matched to controls (n = 67,903) by mother's birth year, country, and county of residence. Odds ratios (ORs) were estimated using conditional logistic regression models adjusting for parity. Older age at first pregnancy, postpartum hemorrhage (OR = 1.18, 95% (confidence interval) CI: 1.08, 1.29), and benign thyroid conditions (ORs ranging from 1.64 for hypothyroidism to 10.35 for thyroid neoplasms) were associated with increased thyroid cancer risk, as were higher offspring birth weight (per 1-kg increase, OR = 1.17, 95% CI: 1.12, 1.22) and higher likelihood of offspring being large for gestational age (OR = 1.26, 95% CI: 1.11, 1.43). Unmarried/noncohabiting status (OR = 0.91, 95% CI: 0.84, 0.98), maternal smoking (OR = 0.75, 95% CI: 0.67, 0.84), and preterm birth (OR = 0.90, 95% CI: 0.83, 0.98) were associated with reduced risk. Several factors (e.g., older age at first pregnancy, maternal smoking, goiter, benign neoplasms, postpartum hemorrhage, hyperemesis gravidarum, and neonatal jaundice) were associated with advanced thyroid cancer. These findings suggest that some perinatal exposures may influence maternal thyroid cancer risk.
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| 10. |
- Modvig, S, et al.
(author)
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Minimal residual disease quantification by flow cytometry provides reliable risk stratification in T-cell acute lymphoblastic leukemia
- 2019
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In: Leukemia. - : Nature Publishing Group. - 0887-6924 .- 1476-5551. ; 33:6, s. 1324-1336
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Journal article (peer-reviewed)abstract
- Minimal residual disease (MRD) measured by PCR of clonal IgH/TCR rearrangements predicts relapse in T-cell acute lymphoblastic leukemia (T-ALL) and serves as risk stratification tool. Since 10% of patients have no suitable PCR-marker, we evaluated flowcytometry (FCM)-based MRD for risk stratification. We included 274 T-ALL patients treated in the NOPHO-ALL2008 protocol. MRD was measured by six-color FCM and real-time quantitative PCR. Day 29 PCR-MRD (cut-off 10-3) was used for risk stratification. At diagnosis, 93% had an FCM-marker for MRD monitoring, 84% a PCR-marker, and 99.3% (272/274) had a marker when combining the two. Adjusted for age and WBC, the hazard ratio for relapse was 3.55 (95% CI 1.4-9.0, p = 0.008) for day 29 FCM-MRD ≥ 10-3 and 5.6 (95% CI 2.0-16, p = 0.001) for PCR-MRD ≥ 10-3 compared with MRD < 10-3. Patients stratified to intermediate-risk therapy on day 29 with MRD 10-4-<10-3 had a 5-year event-free survival similar to intermediate-risk patients with MRD < 10-4 or undetectable, regardless of method for monitoring. Patients with day 15 FCM-MRD < 10-4 had a cumulative incidence of relapse of 2.3% (95% CI 0-6.8, n = 59). Thus, FCM-MRD allows early identification of patients eligible for reduced intensity therapy, but this needs further studies. In conclusion, FCM-MRD provides reliable risk prediction for T-ALL and can be used for stratification when no PCR-marker is available.
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| 11. |
- Ording, Anne Gulbech, et al.
(author)
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Birthweight and all-cause mortality after childhood and adolescent leukemia : a cohort of children with leukemia from Denmark, Norway, Sweden, and Washington State
- 2020
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In: Acta Oncologica. - : TAYLOR & FRANCIS LTD. - 0284-186X .- 1651-226X. ; 59:8, s. 949-958
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Journal article (peer-reviewed)abstract
- Background: High birthweight may predispose children to acute lymphoid leukemia, whereas low birthweight is associated with childhood morbidity and mortality. Low and high birthweight have been inconsistently associated with mortality in children with leukemia. Material and methods: In a cohort of childhood and adolescent leukemia (0-19 years) patients from registries in Denmark, Norway, Sweden, and Washington State in the United States (1967-2015), five-year all-cause mortality was assessed by birthweight and other measures of fetal growth using the cumulative incidence function and Cox regression with adjustment for sex, diagnosis year, country, the presence of Down's syndrome or other malformations, and type of leukemia. Results: Among 7148 children and adolescents with leukemia (55% male), 4.6% were low (<2500 g) and 19% were high (>= 4000 g) birthweight. Compared with average weight, hazard ratios (HRs) of death associated with low birthweight varied by age at leukemia diagnosis: 1.5 (95% confidence interval (CI): 0.7, 3.2) for patients 0-1 year old, 1.6 (95% CI: 1.0, 2.6) for >1-2 years old; 1.0 (95% CI: 0.6, 1.5) for 3-8 years old; 1.0 (95% CI: 0.6, 1.8) for 9-13 years old; and 1.2 (95% CI: 0.7, 2.1) for 14-19 years old, and were similar for size for gestational age and Ponderal index. In analyses restricted to children born full term (37-41 weeks of gestation), results were only slightly attenuated but risk was markedly increased for infants aged <= 1 year (HR for low birthweight = 3.2, 95% CI: 1.2, 8.8). Conclusion: This cohort study does not suggest that low birthweight or SGA is associated with increased five-year all-cause mortality risk among children with any type of childhood leukemia or acute lymphoblastic leukemia, specifically, beyond infancy.
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| 12. |
- Peters, Susan, et al.
(author)
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Narrative review of occupational exposures and noncommunicable diseases
- 2024
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In: ANNALS OF WORK EXPOSURES AND HEALTH. - 2398-7308 .- 2398-7316. ; 68:6, s. 562-580
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Research review (peer-reviewed)abstract
- Objective Within the scope of the Exposome Project for Health and Occupational Research on applying the exposome concept to working life health, we aimed to provide a broad overview of the status of knowledge on occupational exposures and associated health effects across multiple noncommunicable diseases (NCDs) to help inform research priorities.Methods We conducted a narrative review of occupational risk factors that can be considered to have "consistent evidence for an association," or where there is "limited/inadequate evidence for an association" for 6 NCD groups: nonmalignant respiratory diseases; neurodegenerative diseases; cardiovascular/metabolic diseases; mental disorders; musculoskeletal diseases; and cancer. The assessment was done in expert sessions, primarily based on systematic reviews, supplemented with narrative reviews, reports, and original studies. Subsequently, knowledge gaps were identified, e.g. based on missing information on exposure-response relationships, gender differences, critical time-windows, interactions, and inadequate study quality.Results We identified over 200 occupational exposures with consistent or limited/inadequate evidence for associations with one or more of 60+ NCDs. Various exposures were identified as possible risk factors for multiple outcomes. Examples are diesel engine exhaust and cadmium, with consistent evidence for lung cancer, but limited/inadequate evidence for other cancer sites, respiratory, neurodegenerative, and cardiovascular diseases. Other examples are physically heavy work, shift work, and decision latitude/job control. For associations with limited/inadequate evidence, new studies are needed to confirm the association. For risk factors with consistent evidence, improvements in study design, exposure assessment, and case definition could lead to a better understanding of the association and help inform health-based threshold levels.Conclusions By providing an overview of knowledge gaps in the associations between occupational exposures and their health effects, our narrative review will help setting priorities in occupational health research. Future epidemiological studies should prioritize to include large sample sizes, assess exposures prior to disease onset, and quantify exposures. Potential sources of biases and confounding need to be identified and accounted for in both original studies and systematic reviews.
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| 13. |
- Qi, Qibin, et al.
(author)
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FTO genetic variants, dietary intake and body mass index : insights from 177 330 individuals
- 2014
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In: Human Molecular Genetics. - : Oxford University Press (OUP). - 0964-6906 .- 1460-2083. ; 23:25, s. 6961-6972
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Journal article (peer-reviewed)abstract
- FTO is the strongest known genetic susceptibility locus for obesity. Experimental studies in animals suggest the potential roles of FTO in regulating food intake. The interactive relation among FTO variants, dietary intake and body mass index (BMI) is complex and results from previous often small-scale studies in humans are highly inconsistent. We performed large-scale analyses based on data from 177 330 adults (154 439 Whites, 5776 African Americans and 17 115 Asians) from 40 studies to examine: (i) the association between the FTO-rs9939609 variant (or a proxy single-nucleotide polymorphism) and total energy and macronutrient intake and (ii) the interaction between the FTO variant and dietary intake on BMI. The minor allele (A-allele) of the FTO-rs9939609 variant was associated with higher BMI in Whites (effect per allele = 0.34 [0.31, 0.37] kg/m(2), P = 1.9 × 10(-105)), and all participants (0.30 [0.30, 0.35] kg/m(2), P = 3.6 × 10(-107)). The BMI-increasing allele of the FTO variant showed a significant association with higher dietary protein intake (effect per allele = 0.08 [0.06, 0.10] %, P = 2.4 × 10(-16)), and relative weak associations with lower total energy intake (-6.4 [-10.1, -2.6] kcal/day, P = 0.001) and lower dietary carbohydrate intake (-0.07 [-0.11, -0.02] %, P = 0.004). The associations with protein (P = 7.5 × 10(-9)) and total energy (P = 0.002) were attenuated but remained significant after adjustment for BMI. We did not find significant interactions between the FTO variant and dietary intake of total energy, protein, carbohydrate or fat on BMI. Our findings suggest a positive association between the BMI-increasing allele of FTO variant and higher dietary protein intake and offer insight into potential link between FTO, dietary protein intake and adiposity.
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| 14. |
- Sköld, Camilla, et al.
(author)
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Pregnancy-related risk factors for sex cord-stromal tumours and germ cell tumours in parous women : a registry-based study
- 2020
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In: British Journal of Cancer. - : Springer Nature. - 0007-0920 .- 1532-1827. ; 123:1, s. 161-166
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Journal article (peer-reviewed)abstract
- BackgroundNon-epithelial ovarian cancers are divided into sex cord-stromal tumours (SCSTs) and germ cell tumours (GCTs). Whereas parity and other pregnancy-related factors are protective for epithelial ovarian cancer, their associations with SCSTs and GCTs remains unclear.MethodsUsing data from the medical birth registries from Denmark, Finland, Norway and Sweden, we compared all parous women with a diagnosis of SCSTs (n = 420) or GCTs (n = 345) 1970–2013 with up to 10 parous controls (SCSTs n = 4041; GCTs n = 2942) matched on the cases’ birth year and country. We used conditional logistic regression to estimate odds ratios (ORs) with 95% confidence intervals (CIs) of associations between pregnancy-related factors and SCSTs and GCTs.ResultsThe risk of SCSTs, but not GCTs, decreased with higher age at last birth [≥40 versus <25 years: OR 0.48 (95% CI 0.23–0.98)]. The risk of SCSTs (but not GCTs) also decreased with shorter time since last birth. Number of births, preterm birth, preeclampsia, and offspring size were not associated with risk of SCSTs or GCTs.ConclusionsWe found a decreased risk of SCSTs with higher age at last birth and shorter time since last birth. The risk of SCSTs (but not GCTs) may be influenced by the woman’s reproductive history.
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| 15. |
- Sköld, Camilla, et al.
(author)
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Preterm delivery is associated with an increased risk of epithelial ovarian cancer among parous women
- 2018
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In: International Journal of Cancer. - : Wiley. - 0020-7136 .- 1097-0215. ; 143:8, s. 1858-1867
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Journal article (peer-reviewed)abstract
- Epithelial ovarian cancer is a fatal disease of largely unknown etiology. Higher parity is associated with reduced risk of ovarian cancer. However, among parous women, the impact of pregnancy-related factors on risk is not well understood. This population-based case-control study included all parous women with epithelial ovarian cancer in Denmark, Finland, Norway and Sweden during 1967-2013 (n = 10,957) and up to 10 matched controls (n = 107,864). We used conditional logistic regression to estimate odds ratios (ORs) with 95% confidence intervals (CIs) for pregnancy-related factors and ovarian cancer risk by histological subtype. Preterm delivery was associated with an increased risk [pregnancy length (last pregnancy) 30 vs. 39-41 weeks, OR 1.33 (95% CI 1.06-1.67), adjusted for number of births]; the OR increased as pregnancy length decreased (p for trend < 0.001). Older age at first and last birth was associated with a decreased risk [first birth: 30-39 vs. <25 years: adjusted OR 0.76 (95% CI 0.70-0.83); last birth 30-39 vs. <25 years: adjusted OR 0.76 (95% CI 0.71-0.82)]. Increasing number of births was protective [>= 4 births vs. 1; OR 0.63 (95% CI 0.59-0.68)] for all subtypes, most pronounced for clear-cell tumors [OR 0.30, (95% CI 0.21-0.44), p(heterogeneity)<0.001]. No associations were observed for multiple pregnancies, preeclampsia or offspring size. In conclusion, in addition to high parity, full-term pregnancies and pregnancies at older ages were associated with decreased risk of ovarian cancer. Our findings favor the cell clearance hypothesis, i.e. a recent pregnancy provides protection by clearing of precancerous cells from the epithelium of the ovary/fallopian tubes, mediated by placental or ovarian hormones.
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| 16. |
- Slettebø Daltveit, Dagrun, et al.
(author)
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Cancer risk in individuals with major birth defects : large Nordic population based case-control study among children, adolescents, and adults
- 2020
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In: The BMJ. - : BMJ. - 1756-1833. ; 371
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Journal article (peer-reviewed)abstract
- Objective To examine associations between birth defects and cancer from birth into adulthood.Design Population based nested case-control study.Setting Nationwide health registries in Denmark, Finland, Norway, and Sweden.Participants 62 295 cancer cases (0-46 years) and 724 542 frequency matched controls (matched on country and birth year), born between 1967 and 2014.Main outcome measures Relative risk of cancer in relation to major birth defects, estimated as odds ratios with 99% confidence intervals from logistic regression models.Results Altogether, 3.5% (2160/62 295) of cases and 2.2% (15 826/724 542) of controls were born with major birth defects. The odds ratio of cancer for people with major birth defects compared with those without was 1.74 (99% confidence interval 1.63 to 1.84). For individuals with non-chromosomal birth defects, the odds ratio of cancer was 1.54 (1.44 to 1.64); for those with chromosomal anomalies, the odds ratio was 5.53 (4.67 to 6.54). Many structural birth defects were associated with later cancer in the same organ system or anatomical location, such as defects of the eye, nervous system, and urinary organs. The odds ratio of cancer increased with number of defects and decreased with age, for both non-chromosomal and chromosomal anomalies. The odds ratio of cancer in people with any non-chromosomal birth defect was lower in adults (≥20 years: 1.21, 1.09 to 1.33) than in adolescents (15-19 years: 1.58, 1.31 to 1.90) and children (0-14 years: 2.03, 1.85 to 2.23). The relative overall cancer risk among adults with chromosomal anomalies was markedly reduced from 11.3 (9.35 to 13.8) in children to 1.50 (1.01 to 2.24). Among adults, skeletal dysplasia (odds ratio 3.54, 1.54 to 8.15), nervous system defects (1.76, 1.16 to 2.65), chromosomal anomalies (1.50, 1.01 to 2.24), genital organs defects (1.43, 1.14 to 1.78), and congenital heart defects (1.28, 1.02 to 1.59) were associated with overall cancer risk.Conclusions The increased risk of cancer in individuals with birth defects persisted into adulthood, both for non-chromosomal and chromosomal anomalies. Further studies on the molecular mechanisms involved are warranted.
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| 17. |
- Trabert, Britton, et al.
(author)
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Associations of pregnancy-related factors and birth characteristics with risk of endometrial cancer : A Nordic population-based case-control study
- 2020
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In: International Journal of Cancer. - : John Wiley & Sons. - 0020-7136 .- 1097-0215. ; 146:6, s. 1523-1531
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Journal article (peer-reviewed)abstract
- Many pregnancy-related factors are associated with reduced endometrial cancer risk. However, it remains unclear whether pregnancy-related complications (e.g., hypertensive conditions) are associated with risk and whether these associations vary by endometrial cancer subtype. Thus, we evaluated the risk of endometrial cancer, overall and by subtype, in relation to pregnancy-related factors, pregnancy complications and birth characteristics. Utilizing population-based register data from four Nordic countries, we conducted a nested case-control analysis of endometrial cancer risk. We included 10,924 endometrial cancer cases and up to 10 matched controls per case. Odds ratios (ORs) with 95% confidence intervals (CIs) were derived from unconditional logistic regression models. We further evaluated associations by individual histology (i.e., endometrioid, serous, etc.) or, for rare exposures (e.g., pregnancy complications), by dualistic type (Type I [n = 10,343] and Type II [n = 581]). Preexisting and pregnancy-related hypertensive conditions were associated with increased endometrial cancer risk (OR [95% CI]: preexisting hypertension 1.88 [1.39-2.55]; gestational hypertension 1.47 [1.33-1.63]; preeclampsia 1.43 [1.30-1.58]), with consistent associations across dualistic type. Increasing number of pregnancies (≥4 vs. 1 birth: 0.64 [0.59-0.69]) and shorter time since last birth (<10 vs. ≥30 years: 0.34 [0.29-0.40]) were associated with reduced endometrial cancer risk, with consistent associations across most subtypes. Our findings support the role for both hormonal exposures and cell clearance as well as immunologic/inflammatory etiologies for endometrial cancer. This research supports studying endometrial hyperplasia, a precursor condition of endometrial cancer, in the context of pregnancy-related exposures, as this may provide insight into the mechanisms by which pregnancy affects subsequent cancer risk.
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| 18. |
- Troisi, Rebecca, et al.
(author)
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Pregnancy complications and subsequent breast cancer risk in the mother : a Nordic population-based case-control study
- 2018
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In: International Journal of Cancer. - : WILEY. - 0020-7136 .- 1097-0215. ; 143:8, s. 1904-1913
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Journal article (peer-reviewed)abstract
- Certain features of pregnancy are important risk factors for breast cancer, such as protection afforded by young age at first birth. Preeclampsia, a pregnancy complication, is associated with reduced maternal breast cancer risk. However, questions remain regarding causality, biological mechanisms and the relation of other hypertensive conditions to risk. We conducted a population-based case-control study of breast cancer cases (n = 116,196) in parous women identified through linkage of birth and cancer registries in Denmark, Finland, Norway and Sweden (1967-2013), including up to 10 matched controls per case (n = 1,147,192) sampled from the birth registries (complete data were not available on all variables). Odds ratios (ORs) with 95% confidence intervals (CIs) were derived from unconditional logistic regression models including matching factors (country, maternal birth year) and parity. Hypertension diagnosed before pregnancy (OR 0.87; 95% CI 0.78-0.97), gestational hypertension (OR 0.90; 95% CI 0.86-0.93) and preeclampsia (OR 0.91; 95% CI 0.88-0.95) were associated with reduced breast cancer risk. Results remained similar after adjustment for smoking and maternal body mass index before first pregnancy, and were generally similar stratified by parity, age at breast cancer diagnosis, time since first and last birth, sex of the offspring and calendar time. Except for retained placenta (OR 1.14; 95% CI 0.98-1.32), no other pregnancy complication appeared associated with breast cancer risk. The mechanisms mediating the modest risk reductions for history of preeclampsia or hypertension preceding or arising during pregnancy, and possible increased risk with history of retained placenta are unknown and warrant further laboratory, clinical and epidemiological investigation.
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| 19. |
- van der Laan, Sander W., et al.
(author)
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Cystatin C and Cardiovascular Disease : A Mendelian Randomization Study
- 2016
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In: Journal of the American College of Cardiology. - : Elsevier BV. - 0735-1097 .- 1558-3597. ; 68:9, s. 934-945
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Journal article (peer-reviewed)abstract
- BACKGROUND Epidemiological studies show that high circulating cystatin C is associated with risk of cardiovascular disease (CVD), independent of creatinine-based renal function measurements. It is unclear whether this relationship is causal, arises from residual confounding, and/or is a consequence of reverse causation. OBJECTIVES The aim of this study was to use Mendelian randomization to investigate whether cystatin C is causally related to CVD in the general population. METHODS We incorporated participant data from 16 prospective cohorts (n = 76,481) with 37,126 measures of cystatin C and added genetic data from 43 studies (n = 252,216) with 63,292 CVD events. We used the common variant rs911119 in CST3 as an instrumental variable to investigate the causal role of cystatin C in CVD, including coronary heart disease, ischemic stroke, and heart failure. RESULTS Cystatin C concentrations were associated with CVD risk after adjusting for age, sex, and traditional risk factors (relative risk: 1.82 per doubling of cystatin C; 95% confidence interval [CI]: 1.56 to 2.13; p = 2.12 x 10(-14)). The minor allele of rs911119 was associated with decreased serum cystatin C (6.13% per allele; 95% CI: 5.75 to 6.50; p = 5.95 x 10(-211)), explaining 2.8% of the observed variation in cystatin C. Mendelian randomization analysis did not provide evidence fora causal role of cystatin C, with a causal relative risk for CVD of 1.00 per doubling cystatin C (95% CI: 0.82 to 1.22; p = 0,994), which was statistically different from the observational estimate (p = 1.6 x 10(-5)). A causal effect of cystatin C was not detected for any individual component of CVD. CONCLUSIONS Mendelian randomization analyses did not support a causal role of cystatin C in the etiology of CVD. As such, therapeutics targeted at lowering circulating cystatin C are unlikely to be effective in preventing CVD.
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| 20. |
- Wijk, Ingrid
(author)
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Experiences of living with type 1 diabetes and improving psychological flexibility through an Acceptance and Commitment Therapy (ACT) intervention
- 2023
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Doctoral thesis (other academic/artistic)abstract
- Background: Impaired psychological health in type 1 diabetes is prevalent and associated with elevated glycaemic outcomes. International evidence-based guidelines have defined glycaemic treatment targets to prevent acute and long-term complications. In addition, the guidelines encourage screening for the elevated distress that living with type 1 diabetes may imply. There is a need to gain further understanding of what it means to live with type 1 diabetes as an adult with elevated HbA1c and to develop interventions to promote psychological and physiological health.Aim: The overall aim of the thesis was to describe experiences of living with type 1 diabetes as an adult with elevated HbA1c and furthermore to evaluate the impact of an Acceptance and Commitment Therapy programme for people living with type 1 diabetes. The thesis also aimed to examine the Swedish version of Acceptance and Action Diabetes Questionnaire (AADQ), which is a questionnaire for psychological flexibility related to diabetes.Method and result: In Study I we included 81 adults with type 1 diabetes and HbA1c > 60 mmol/mol in a randomised controlled trial. A seven-session programme based on Acceptance and Commitment Therapy was conducted and the impact on HbA1c, self-management and psychosocial factors was evaluated. No effect was demonstrated in the linear mixed model analysis on HbA1c or the secondary outcomes. Nevertheless, a significant statistical improvement in psychological flexibility was noted one and two years after the intervention. A large drop-out rate was observed in the study. In Study II, the psychometric properties of a translated version of the AADQ were examined through Rasch analysis. A total of 120 adults with type 1 diabetes were included. The Swedish version of the ADDQ showed acceptable psychometric properties such as fit to the Rasch model and person separation index. However, we also found indications on a malfunctioning categorisation of the response categories. A collapsed three category rating was examined. In Study III, two categories of experiences were described in the qualitative interviews: constraining and manageable. Through content analysis, an overarching theme was created "a life-long follower". The theme describes the unrelenting existence of type 1 diabetes that impact life in various degrees.Conclusion: No impact on HbA1c or secondary outcomes could be demonstrated through the Acceptance and Commitment Therapy based programme. At the same time, a key component in psychological health, psychological flexibility, was improved. The Swedish version of the AADQ showed acceptable psychometric quality. However, uncertainties regarding the categorisation should be further examined. The experiences of living with type 1 diabetes as an adult and elevated HbA1c is widely diverse. A person-centred care approach is therefore crucial to support the needs of each unique person with type 1 diabetes.
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| 21. |
- Wijk, Ingrid, et al.
(author)
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Impact of an acceptance and commitment therapy programme on HbA1c, self-management and psychosocial factors in adults with type 1 diabetes and elevated HbA1c levels : a randomised controlled trial
- 2023
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In: BMJ Open. - : BMJ Publishing Group Ltd. - 2044-6055. ; 13:12, s. e072061-
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Journal article (peer-reviewed)abstract
- Objective: To evaluate the impact of an Acceptance and Commitment Therapy (ACT) programme, tailored for people living with type 1 diabetes, on glycated haemoglobin (HbA1c), self-management and psychosocial factors among individuals with HbA1c>60 mmol/mol compared with treatment as usual (TAU). Setting: An endocrinologic clinic in Sweden. Participants: In this randomised controlled trial, 81 individuals with type 1 diabetes, aged 18–70 years with HbA1c>60 mmol/mol, were randomly assigned to either an ACT group intervention or TAU. Exclusion criteria were: unable to speak Swedish, untreated or severe psychiatric disease, cortisone treatment, untreated thyroid disease and newly started insulin pump therapy. At the 2-year follow-up, HbA1c was measured in 26 individuals. Intervention: The ACT programme comprised seven 2-hour sessions held over 14 weeks and focused on acceptance of stressful thoughts and emotions, and to promote value-based committed action. Outcomes: The primary outcome was HbA1c, and the secondary outcomes were measures of depression, anxiety, general stress, fear of hypoglycaemia, diabetes distress, self-care activities, psychological flexibility (general and related to diabetes) and quality of life. The primary endpoint was HbA1c 2 years after the intervention programme. Linear mixed models were used to test for an interaction effect between measurement time and group. Results: Likelihood ratio test of nested models demonstrated no statistically significant interaction effect (χ2=0.49, p=0.485) between measurement time and group regarding HbA1c. However, a statistically significant interaction effect (likelihood ratio test χ2=12.63, p<0.001) was observed with improved scores on The Acceptance and Action Questionnaire in the intervention group after 1 and 2 years. Conclusions: No statistically significant difference was found between the groups regarding the primary outcome measure, HbA1c. However, the ACT programme showed a persistent beneficial impact on psychological flexibility in the intervention group. The dropout rate was higher than expected, which may indicate a challenge in this type of study. Trial registration number NCT02914496.
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| 22. |
- Wijk, Ingrid, et al.
(author)
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Living with Type 1 Diabetes as Experienced by Adults with Prolonged Elevated HbA1c : A Qualitative Study
- 2023
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In: Diabetes Therapy. - : Springer Nature. - 1869-6953 .- 1869-6961. ; 14, s. 1673-1684
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Journal article (peer-reviewed)abstract
- Introduction: High HbA1c levels in type 1 diabetes (T1D) are associated with increased risk of micro- and macrovascular complications and severe diabetes distress. A more comprehensive understanding of the adult perspective of living with T1D can improve the quality of care. We aimed to describe experiences of living with T1D as an adult with prolonged elevated HbA1c.Methods: Thirteen adults with T1D and HbA1c > 60 mmol/mol (7.6%) for at least 1 year were individually interviewed via a digital platform. The interviews were transcribed verbatim and analyzed using qualitative content analysis.Results: The analysis identified an overarching theme, “a lifelong follower”, and generated two main categories describing study participants’ experience: constraining and manageable. Constraining experiences were explained in obligated control, loss of control, environmental impact, and consequences of diabetes. Manageable experiences were described in everyday life, approach to diabetes, and support in life. Diabetes knowledge in health care and in the general public, and individualized care were important factors in feeling understood, safe, and supported.Conclusions: The findings revealed the diverse experiences of adults with prolonged elevated HbA1c. Living with T1D, a lifelong non-chosen follower, could be perceived as constraining but manageable in different degrees. A person-centered care approach addressing both dimensions may be beneficial. Experiences of living with and managing diabetes are multifaceted and intertwined with life context and medical prerequisites.
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| 23. |
- Wijk, Ingrid, et al.
(author)
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Psychometric Evaluation of the Swedish Acceptance and Action Diabetes Questionnaire : A Rasch Analysis
- 2023
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In: Journal of Nursing Measurement. - 1061-3749 .- 1945-7049.
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Journal article (peer-reviewed)abstract
- Background and purpose: The Acceptance and Action Diabetes Questionnaire (AADQ) is a tool for assessing the acceptance of thoughts and emotions related to diabetes in people living with the disease. This study aimed to examine the psychometric properties of the Swedish version of AADQ (Swe-AADQ) in a sample of adults with type 1 diabetes. Methods: To examine the psychometric properties of the Swe-AADQ, the Rasch model was used. Data for 120 individuals were included. Results: The Swe-AADQ showed an acceptable fit to the Rasch model. A sufficiently high value of the separation index indicated a capacity to distinguish between different levels of acceptance in the sample. The seven-point Likert scale was reduced to three categories suggesting an improvement in the ordering of the item thresholds. Conclusions: The Swe-AADQ possesses reasonable quality in terms of reliability and validity. However, there are some deficiencies regarding the categorization of the response rating that should be addressed.
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| 24. |
- Wijk, Ingrid, et al.
(author)
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Psychometric evaluation of the Swedish Acceptance and Action Diabetes Questionnaire : A Rasch analysis
- 2023
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In: Journal of Nursing Measurement. - 1061-3749 .- 1945-7049.
-
Journal article (peer-reviewed)abstract
- Background and purpose: The Acceptance and Action Diabetes Questionnaire (AADQ) is a tool for assessing the acceptance of thoughts and emotions related to diabetes in people living with the disease. This study aimed to examine the psychometric properties of the Swedish version of AADQ (Swe-AADQ) in a sample of adults with type 1 diabetes.Methods: To examine the psychometric properties of the Swe-AADQ, the Rasch model was used. Data for 120 individuals were included.Results: The Swe-AADQ showed an acceptable fit to the Rasch model. A sufficiently high value of the separation index indicated a capacity to distinguish between different levels of acceptance in the sample. The seven-point Likert scale was reduced to three categories suggesting an improvement in the ordering of the item thresholds.Conclusions: The Swe-AADQ possesses reasonable quality in terms of reliability and validity. However, there are some deficiencies regarding the categorization of the response rating that should be addressed.
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