Linda Vos

Parity, hormones and breast cancer subtypes - results from a large nested case-control study in a national screening program

BackgroundBreast cancer comprises several molecular subtypes with different prognoses and possibly different etiology. Reproductive and hormonal factors are associated with breast cancer overall, and with luminal subtypes, but the associations with other subtypes are unclear. We used data from a national screening program to conduct a large nested case-control study.MethodsWe conducted a nested case-control study on participants in the Norwegian Breast Cancer Screening Program in 2006 − 2014. There was information on estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor 2 (HER2) for 4748 cases of breast cancer. Breast cancer subtypes were defined as luminal A-like (ER+ PR+ HER2-), luminal B-like (ER+ PR- HER2- or ER+ PR+/PR-HER2+), HER2-positive (ER- PR- HER2+) and triple-negative (ER- PR- HER2-). Conditional logistic regression was used to estimate odds ratios (ORs) of breast cancer associated with age at first birth, number of pregnancies, oral contraceptive use, intrauterine devices and menopausal hormone therapy. Analyses were adjusted for age, body mass index, education, age at menarche, number of pregnancies and menopausal status.ResultsNumber of pregnancies was inversely associated with relative risk of luminal-like breast cancers (p-trend ≤0.02), and although not statistically significant, with HER2-positive (OR = 0.60, 95% CI 0.31–1.19) and triple-negative cancer (OR = 0.70, 95% CI 0.41–1.21). Women who had ≥4 pregnancies were at >40% lower risk of luminal-like and HER2-positive cancers than women who had never been pregnant. However, there was a larger discrepancy between tumor subtypes with menopausal hormone use. Women who used estrogen and progesterone therapy (EPT) had almost threefold increased risk of luminal A-like cancer (OR = 2.92, 95% CI 2.36–3.62) compared to never-users, but were not at elevated risk of HER2-positive (OR = 0.88, 95% CI 0.33–2.30) or triple-negative (OR = 0.92, 95% CI 0.43 − 1.98) subtypes.ConclusionsReproductive factors were to some extent associated with all subtypes; the strongest trends were with luminal-like subtypes. Hormone therapy use was strongly associated with risk of luminal-like breast cancer, and less so with risk of HER2-positive or triple-negative cancer. There are clearly some, but possibly limited, etiologic differences between subtypes, with the greatest contrast between luminal A-like and triple-negative subtypes.Trial registrationNot applicable.

Measured cardiorespiratory fitness and self‐reported physical activity: associations with cancer risk and death in a long‐term prospective cohort study

Physical activity is inversely associated with risk of some cancers. The relation with cancer‐specific death remains uncertain. Mainly, studies on relationships between physical activity and cancer are based on self‐reported physical activity (SPA). Hereby, we examined whether measured cardiorespiratory fitness (CRF) is associated with cancer risk, mortality, and case fatality. We also describe relationships between SPA and these outcomes, and between CRF and SPA. A cohort of 1997 healthy Norwegian men, aged 40–59 years at inclusion in 1972–75, was followed throughout 2012. At baseline, CRF was objectively measured. SPA (leisure time and occupational) was obtained through a questionnaire. Relationships between CRF or SPA, and the outcomes were estimated using Cox regression, adjusted for age, body mass index (BMI), and smoking. Pearson correlation coefficients evaluated agreements between CRF and SPA. During follow‐up, 758 men were diagnosed with cancer and 433 cancer deaths occurred. Analyses revealed lower cancer risk (Hazard ratio [HR] 0.85, 95% confidence intervals [CI]: 0.68–1.00), mortality (HR 0.68, 95% CI: 0.53–0.88), and case fatality (HR 0.74, 95% CI: 0.57–0.96), in men with high CRF compared to low CRF. Light leisure time SPA was associated with lower cancer risk (HR 0.70, 95% CI: 0.56–0.86) and mortality (HR 0.64 95% CI: 0.49–0.83), whereas strenuous occupational SPA was associated with higher risks (HR 1.42, 95% CI: 1.13–1.78 and HR 1.45, 95% CI: 1.09–1.93). Correlations between CRF and SPA were 0.351 (P < 0.001) and −0.106 (P < 0.001) for leisure time and occupational SPA, respectively. A high midlife CRF may be beneficial for cancer risk, cancer mortality, and case fatality.

Pricing of forwards and options in a multivariate non-Gaussian stochastic volatility model for energy markets

In Benth and Vos (2013) we introduced a multivariate spot price model with stochastic volatility for energy markets which captures characteristic features, such as price spikes, mean reversion, stochastic volatility, and inverse leverage effect as well as dependencies between commodities. In this paper we derive the forward price dynamics based on our multivariate spot price model, providing a very flexible structure for the forward curves, including contango, backwardation, and hump shape. Moreover, a Fourier transform-based method to price options on the forward is described.

Vitamin D intake, month the mammogram was taken and mammographic density in Norwegian women aged 50-69

Background The role of vitamin D in breast cancer etiology is unclear. There is some, but inconsistent, evidence that vitamin D is associated with both breast cancer risk and mammographic density (MD). We evaluated the associations of MD with month the mammogram was taken, and with vitamin D intake, in a population of women from Norway—a country with limited sunlight exposure for a large part of the year. Methods 3114 women aged 50–69, who participated in the Norwegian Breast Cancer Screening Program (NBCSP) in 2004 or 2006/07, completed risk factor and food frequency (FFQ) questionnaires. Dietary and total (dietary plus supplements) vitamin D, calcium and energy intakes were estimated by the FFQ. Month when the mammogram was taken was recorded on the mammogram. Percent MD was assessed using a computer assisted method (Madena, University of Southern California) after digitization of the films. Linear regression models were used to investigate percent MD associations with month the mammogram was taken, and vitamin D and calcium intakes, adjusting for age, body mass index (BMI), study year, estrogen and progestin therapy (EPT), education, parity, calcium intakes and energy intakes. Results There was no statistical significant association between the month the mammogram was taken and percent MD. Overall, there was no association between percent MD and quartiles of total or dietary vitamin D intakes, or of calcium intake. However, analysis restricted to women aged <55 years revealed a suggestive inverse association between total vitamin D intake and percent MD (p for trend = 0.03). Conclusion Overall, we found no strong evidence that month the mammogram was taken was associated with percent MD. We found no inverse association between vitamin D intake and percent MD overall, but observed a suggestive inverse association between dietary vitamin D and MD for women less than 55 years old.

Cross-commodity spot price modeling with stochastic volatility and leverage for energy markets

Spot prices in energy markets exhibit special features, such as price spikes, mean reversion, stochastic volatility, inverse leverage effect, and dependencies between the commodities. In this paper a multivariate stochastic volatility model is introduced which captures these features. The second-order structure and stationarity of the model are analyzed in detail. A simulation method for Monte Carlo generation of price paths is introduced and a numerical example is presented.

Hyperemesis gravidarum and long-term mortality: a population-based cohort study

To investigate whether exposure to hyperemesis gravidarum (HG) is associated with increased maternal long‐term mortality.

Cause-specific mortality and cancer morbidity in 390 male workers exposed to high purity talc, a six-decade follow-up

BACKGROUND This study updates information on mortality and cancer morbidity in a cohort of Norwegian talc workers. METHODS Follow-up was extended with 24 years, covering 1953-2011. Comparisons were made with the general population and between subgroups within the cohort. RESULTS Standardized mortality ratio for non-malignant respiratory disease (NMRD) was 0.38 (95%CI: 0.18, 0.69) and for diseases of the circulatory system (CVD) 0.98 (95%CI: 0.82, 1.16). A non-significantly increased NMRD risk was observed at high dust exposures. There were no deaths from pneumoconiosis. CONCLUSIONS With the clear limitations of a small cohort, our results do hint at an effect of talc dust on mortality from NMRD other than pneumoconiosis, covered by a strong and persisting healthy worker effect. Also, an effect on CVD mortality, masked by a healthy worker selection into the cohort cannot be ruled out. Excess mortality from pneumoconiosis seen in other studies, may reflect exposure to quartz and, possibly, bias due to comparability problems.

Alcohol, Physical Activity, Smoking, and Breast Cancer Subtypes in a Large, Nested Case–Control Study from the Norwegian Breast Cancer Screening Program

Background: To what extent alcohol, smoking, and physical activity are associated with the various subtypes of breast cancer is not clear. We took advantage of a large population-based screening cohort to determine whether these risk factors also increase the risk of the poor prognosis subtypes. Methods: We conducted a matched case–control study nested within the Norwegian Breast Cancer Screening Program during 2006–2014. A total of 4,402 breast cancer cases with risk factor and receptor data were identified. Five controls were matched to each case on year of birth and year of screening. Conditional logistic regression was used to estimate ORs of breast cancer subtypes adjusted for potential confounders. Results: There were 2,761 luminal A–like, 709 luminal B–like HER2-negative, 367 luminal B–like HER2-positive, 204 HER2-positive, and 361 triple-negative cancers. Current alcohol consumption was associated with breast cancer risk overall [OR 1.26; 95% confidence interval (CI), 1.09–1.45] comparing 6+ glasses a week to never drinkers. However, this risk increase was found only for luminal A–like breast cancer. Smoking 20+ cigarettes a day was associated with an OR of 1.41 (95% CI, 1.06–1.89) overall, with significant trends for luminal A–like and luminal B–like HER2-negative cancer. Current physical activity (4+ hours/week compared with none) was associated with 15% decreased risk of luminal A–like cancer, but not clearly with other subtypes. Conclusions: In this large study, alcohol, smoking, and physical activity were predominantly associated with luminal A–like breast cancer. Impact: Alcohol, smoking, and physical activity were associated with luminal A–like breast cancer subtype. Cancer Epidemiol Biomarkers Prev; 26(12); 1736–44. ©2017 AACR.

A protocol for prospective studies of 25-hydroxyvitamin D, leptin and body mass index in relation to cutaneous melanoma incidence and survival

Introduction The incidence and mortality rates of cutaneous melanoma (CM) are increasing among fair-skinned populations worldwide. Ultraviolet radiation (UVR) is the principal risk factor for CM, but is also the main source of 25-hydroxyvitamin D (25(OH)D), which has been associated with reduced risk and better prognosis of some cancer types. However, both low and high 25(OH)D levels have been associated with increased risk of CM. Obesity as measured by body mass index (BMI) is associated with risk of several cancers and has also been suggested as a risk factor for CM, and may also be related to insufficient 25(OH)D and/or high leptin levels. Moreover, contracting a CM diagnosis has been associated with increased risk of developing second cancer. We aim to study whether low prediagnostic serum levels of 25(OH)D, high prediagnostic levels of BMI and high serum leptin levels influence CM incidence, Breslow thickness and CM mortality, and risk of second cancer and survival after a CM diagnosis. Methods and analysis Cohort and nested case–control studies will be carried out using the population-based Janus Serum Bank Cohort (archival prediagnostic sera, BMI, smoking and physical activity), with follow-up from 1972 to 2014. Additional data will be received from the Cancer Registry of Norway, the national Cause of Death Registry, Statistics Norway (education and occupation) and exposure matrices of UVR. Time-to-event regression models will be used to analyse the cohort data, while the nested case–control studies will be analysed by conditional logistic regression. A multilevel approach will be applied when incorporating group-level data. Ethics and dissemination The project is approved by the Regional Committee for Medical Research Ethics and is funded by the Norwegian Cancer Society. Results will be published in peer-reviewed journals, at scientific conferences and in the news media.

High mortality due to cutaneous melanoma in Norway: a study of prognostic factors in a nationwide cancer registry

Purpose The purpose of this study was to examine why Norway has the highest rate of mortality due to cutaneous melanoma (CM) in Europe. The Norwegian Malignant Melanoma Registry (NMMR) enables the study of clinical and histopathological characteristics of patients who die due to CM. Results The NMMR and the Norwegian Cause of Death Registry provided data on the clinical and histopathological factors as well as the date and cause of death, through June 2015 for all first invasive CMs diagnosed in 2008–2012 (n=8087). Cox regression was used to estimate associations between clinical and pathological factors and CM-specific death. Multiple imputation was used to handle missing data. Results The CMs were equally distributed between men (49.9%) and women (50.1%), and the median follow-up was 4.0 years (range: 0.08–7.5 years). Trunk was the most common anatomic site (48%), superficial spreading melanoma was the dominant melanoma subtype (68.2%), median Breslow thickness was 1.0 mm, ulceration was present in 23% of CMs, and 91.8% of cases were in a local clinical stage at diagnosis. Compared to women, men were diagnosed at a higher age, with thicker and more-often-ulcerated tumor, and more often were in advanced clinical stages. During follow-up, 1015 patients died due to CM, representing 52.8% of all deaths. The nodular subtype made up the dominant proportion of fatal CM cases (55.3% in women, 64.6% in men). Sex, age, anatomic site (trunk), T-stage, ulceration, clinical stage, and having a second primary CM were associated with increased risk of CM-specific death. Conclusion Our data suggest that the high rate of mortality due to CM observed in Norway is attributable to the more advanced stage of the disease at diagnosis. Most high-risk cases occurred in male patients ≥70 years of age. Efforts to improve awareness and secondary prevention of CM, including warning signs of all melanoma subtypes, are required urgently and should be targeted toward men in particular.