This book introduces systems epidemiology, which is a new scientific discipline borne by novel technologies. These have opened up the potential for studies of temporal changes in the carcinogenic ...process and the response of the immune system, all measured as functional genomics: gene expression, microRNA and methylation. Systems epidemiology is an integrated approach based on epidemiological methods with biobanks designed for studies of the trajectories or curves of functional genomics moving from before diagnosis, at diagnosis and postdiagnostic. It demands new epidemiological designs, the globolomic one, new statistical methods for description and analyses of time changes and incorporating basic knowledge from reductionist experiments and clinical outcomes including molecular biomarkers of cancer tissue and normal tissues.
We examined the association between active and passive smoking and lung cancer risk and the population attributable fraction (PAF) of lung cancer due to active smoking, in the Norwegian Women and ...Cancer Study, a nationally representative prospective cohort study.
We followed 142,508 women, aged 31-70 years, who completed a baseline questionnaire between 1991 and 2007, through linkages to national registries through December 2015. We used Cox proportional hazards models, to estimate hazard ratios (HRs) with 95% confidence intervals (CIs). We calculated PAF to indicate what proportion of lung cancer cases could have been prevented in the absence of smoking.
During the more than 2.3 million person-years of observation, we ascertained 1507 lung cancer cases. Compared with never smokers, current (HR 13.88, 95% CI 10.18-18.91) smokers had significantly increased risk of lung cancer. Female never smokers exposed to passive smoking had a 1.3-fold (HR 1.34, 95% CI 0.89-2.01) non- significantly increased risk of lung cancer, compared with never smokers. The PAF of lung cancer was 85.3% (95% CI 80.0-89.2).
More than 8 in 10 lung cancer cases could have been avoided in Norway, if the women did not smoke.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Abstract
Background
Body fatness is a dynamic exposure throughout life. To provide more insight into the association between body mass index (BMI) and postmenopausal breast cancer, we aimed to ...examine the age at onset, duration, intensity, and trajectories of body fatness in adulthood in relation to risk of breast cancer subtypes.
Methods
Based on self-reported anthropometry in the prospective Norwegian Women and Cancer Study, we calculated the age at onset, duration, and intensity of overweight and obesity using linear mixed-effects models. BMI trajectories in adulthood were modeled using group-based trajectory modeling. We used Cox proportional hazards models to calculate hazard ratios (HRs) with 95% confidence intervals (CIs) for the associations between BMI exposures and breast cancer subtypes in 148,866 postmenopausal women.
Results
A total of 7223 incident invasive postmenopausal breast cancer cases occurred during follow-up. Increased overweight duration and age at the onset of overweight or obesity were associated with luminal A-like breast cancer. Significant heterogeneity was observed in the association between age at overweight and overweight duration and the intrinsic-like subtypes (
p
heterogeneity
0.03). Compared with women who remained at normal weight throughout adulthood, women with a descending BMI trajectory had a reduced risk of luminal A-like breast cancer (HR 0.54, 95% CI 0.33–0.90), whereas women with ascending BMI trajectories were at increased risk (HR 1.09; 95% CI 1.01–1.17 for “Normal-overweight”; HR 1.20; 95% CI 1.07–1.33 for “Normal-obesity”). Overweight duration and weighted cumulative years of overweight and obesity were inversely associated with luminal B-like breast cancer.
Conclusions
In this exploratory analysis, decreasing body fatness from obesity in adulthood was inversely associated with overall, hormone receptor-positive and luminal A-like breast cancer in postmenopausal women. This study highlights the potential health benefits of reducing weight in adulthood and the health risks associated with increasing weight throughout adult life. Moreover, our data provide evidence of intrinsic-like tumor heterogeneity with regard to age at onset and duration of overweight.
MicroRNAs (miRNAs) are promising biomarkers due to their structural stability and distinct expression profile in various cancers. We wanted to explore the miRNA expression in benign breast tissue and ...breast cancer subgroups in the Norwegian Women and Cancer study.
Specimens and histopathological data from study participants in Northern Norway diagnosed with breast cancer, and benign tissue from breast reduction surgery were collected. Main molecular subtypes were based on surrogate markers; luminal A (ER+ and/or PR+, HER2- and Ki67 ≤ 30%), luminal B (ER+ and/or PR+, HER2- and Ki67 > 30% or ER+ and/or PR+ and HER2+), HER2 positive (ER- and PR- and HER2+) and triple-negative (ER-, PR- and HER2-). RNA was extracted from formalin-fixed paraffin-embedded (FFPE) tissue, and miRNAs were successfully analyzed in 102 cancers and 36 benign controls using the 7th generation miRCURY LNA microarray containing probes targeting all human miRNAs as annotated in miRBASE version 19.0. Validation with RT-qPCR was performed.
On average, 450 miRNAs were detected in each sample, and 304 miRNAs were significantly different between malignant and benign tissue. Subgroup analyses of cancer cases revealed 23 miRNAs significantly different between ER+ and ER- tumors, and 47 miRNAs different between tumors stratified according to grade. Significantly higher levels were found in high grade tumors for miR-17-5p (p = 0.006), miR-20a-5p (p = 0.007), miR-106b-5p (p = 0.007), miR-93-5p (p = 0.007) and miR-25-3p (p = 0.015) from the paralogous clusters miR-17-92 and miR-106b-25. Expression of miR-17-5p (p = 0.0029), miR-20a-5p (p = 0.0021), miR-92a-3p (p = 0.011) and miR-106b-5p (p = 0.021) was significantly higher in triple-negative tumors compared to the rest, and miR-17-5p and miR-20a-5p were significantly lower in luminal A tumors.
miRNA expression profiles were significantly different between malignant and benign tissue and between cancer subgroups according to ER- status, grade and molecular subtype. miRNAs in the miR-17-92 cluster and miR-17 family were overexpressed in high grade and triple-negative tumors associated with aggressive behavior. The expression and functional role of these miRNAs should be further studied in breast cancer to explore their potential as biomarkers in diagnostic pathology and clinical oncology.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Purpose To assess melanoma risk in relation to sunscreen use and to compare high- with low-sun protection factor (SPF) sunscreens in relation to sunbathing habits in a large cohort study. Materials ...and Methods We used data from the Norwegian Women and Cancer Study, a prospective population-based study of 143,844 women age 40 to 75 years at inclusion with 1,532,247 person-years of follow-up and 722 cases of melanoma. Multivariable Cox proportional hazards regression was used to estimate the association between sunscreen use (never, SPF < 15, SPF ≥ 15) and melanoma risk by calculating hazard ratios and 95% CIs. The population attributable fraction associated with sunscreen use was estimated. Results Sunscreen users reported significantly more sunburns and sunbathing vacations and were more likely to use indoor tanning devices. SPF ≥ 15 sunscreen use was associated with significantly decreased melanoma risk compared with SPF < 15 use (hazard ratio, 0.67; 95% CI, 0.53 to 0.83). The estimated decrease in melanoma (population attributable fraction) with general use of SPF ≥ 15 sunscreens by women age 40 to 75 years was 18% (95% CI, 4% to 30%). Conclusion Use of SPF ≥ 15 rather than SPF < 15 sunscreens reduces melanoma risk. Moreover, use of SPF ≥ 15 sunscreen by all women age 40 to 75 years could potentially reduce their melanoma incidence by 18%.
Recent studies have indicated that there are functional genomic signals that can be detected in blood years before cancer diagnosis. This study aimed to assess gene expression in prospective blood ...samples from the Norwegian Women and Cancer cohort focusing on time to lung cancer diagnosis and metastatic cancer using a nested case-control design. We employed several approaches to statistically analyze the data and the methods indicated that the case-control differences were subtle but most distinguishable in metastatic case-control pairs in the period 0-3 years prior to diagnosis. The genes of interest along with estimated blood cell populations could indicate disruption of immunological processes in blood. The genes identified from approaches focusing on alterations with time to diagnosis were distinct from those focusing on the case-control differences. Our results support that explorative analyses of prospective blood samples could indicate circulating signals of disease-related processes.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Parabens are used extensively in personal care products; however, their estrogenic properties have raised concern over risks to human health. High levels of total parabens, mainly as conjugates, have ...been reported in human plasma/serum, with limited data on native parabens. Our objective was to assess and link plasma concentrations of native common parabens to self-reported use of personal care products in women from the general population. The information was obtained from an extensive questionnaire on diet and lifestyle previously answered by the women in the NOWAC study. Plasma samples from 332 individuals were extracted and cleaned up by automated solid phase extraction and analyzed by ultra high performance liquid chromatography time-of-flight mass spectrometry. Native methyl paraben dominated and was detected in 63% of the samples, with a median level of 9.4 ng/ml. Ethyl paraben (median < 3 ng/ml) and propyl paraben (median < 2 ng/ml) were detected in 22 and 29%, respectively. Butyl and benzyl parabens were not detected. For the first time, elevated levels of native parabens are reported in women from the general population. The concentrations were significantly associated with the use of skin lotions, indicating that frequent (daily or more) use maintain elevated concentrations despite the parabens short half-lives. These findings clearly emphasize the need to study potential health effects in the general population.
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DOBA, EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, IZUM, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UILJ, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
The effects of fish consumption and n-3 fatty acids on type 2 diabetes mellitus (T2DM) have recently been debated.
We explored the risk of T2DM in relation to consumption of lean fish, fatty fish, ...fish products and total fish as well as cod liver oil supplements in a representative sample of Norwegian women.
This was a prospective population based cohort study in 33740 women free of T2DM, stroke, angina or heart attack and with detailed information on important co-variates and dietary intake at baseline. Risk ratios and corresponding 95% CI were estimated using Poisson regression with log-person time as offset.
Lean fish consumption was inversely associated with T2DM compared to zero intake. Risk ratios and 95% CI for intake of 75 and 100 g lean fish per day were 0.71 (0.51, 0.98) and 0.67 (0.46, 0.98), respectively. There was no effect of intake of fatty fish, fish products, total fish or use of cod liver oil supplements on the risk of T2DM.
Lean fish consumption of 75-100 g/d had a beneficial effect on T2DM. It remains unclear whether lean fish in itself has a protective effect on T2DM or that lean fish consumers have a protective life-style that we were not able to take into account in this study. Unfavorable effects of fatty fish consumption or use of cod liver oil supplements on T2DM were not observed.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
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