Reproductive Factors, Use of Exogenous Hormones, and Pancreatic Cancer Incidence: The Norwegian Women and Cancer Study

Introduction: The incidence of pancreatic cancer is increasing worldwide and characterized by a particularly low survival rate. Studies have reported weak and inconsistent evidence for associations among reproductive factors, use of exogenous hormones, and pancreatic cancer incidence in women. Purpose: To investigate relationships between reproductive factors, exogenous hormones, and the rate of pancreatic cancer incidence in a large population-based prospective cohort of women in Norway. Methods: We used data from the Norwegian Women and Cancer study on 588 incident cases of pancreatic cancer diagnosed among 165,419 women, with mean follow-up of 18.7 years. Cox proportional-hazard models were used to estimate HRs and 95% CIs for associations of interest. Results: Cumulative breastfeeding duration > 24 months was associated with 63% decreased incidence of pancreatic cancer compared to no breastfeeding. We observed an inverse linear dose–response trend between cumulative breastfeeding duration and pancreatic cancer incidence, which was confirmed in parous women and ever-smokers. Higher age at first birth and menopause were inversely associated with pancreatic cancer incidence, though with less precise effect estimates. Current use of oral contraceptives was associated with a doubling of pancreatic cancer incidence, but the analysis was hampered by a small number of cases. There was no evidence of any associations between age at menarche, parity or use of menopausal hormone therapy, and incidence of pancreatic cancer. Conclusion: Our results suggest a potential protective effect of breastfeeding duration against pancreatic cancer incidence. Inconsistent results for the other reproductive factors suggested no important role of estrogens in pancreatic cancer etiology

Dietary patterns in relation to incidence rate of pancreatic cancer – the Norwegian women and cancer cohort study.

Despite development in cancer treatment and prevention options during the past few years, cancer of the pancreas remains a diagnosis associated with poor prognosis and limited options for prevention. Diet has proven to be an important risk factor for development of many types of cancer, particularly for cancers of the digestive system. Still, evidence regarding its relation to pancreatic cancer remains ambiguous. To investigate the relationship between diet and pancreatic cancer, an analysis of dietary patterns in participants from the Norwegian Women and Cancer Study (n = 89,156; 305 pancreatic cancer cases) was performed. Cox regression analysis was used for studying possible associations between dietary patterns, derived from principal component analysis, and pancreatic cancer incidence. The four most prominent dietary patterns were identified and described: European pattern, animal food consumers’ dietary pattern, traditional Norwegian pattern, and alcohol-abstaining dietary pattern. In analysis without adjustment for confounders, being in the highest tertile of the abstaining dietary pattern was associated with lower risk of pancreatic cancer in comparison to the lowest tertile (hazard ratios [HR]: 0.66, 95% confidence interval [CI]: 0.49–0.89). After additional adjustment for height and smoking status, no dietary pattern was associated with increased pancreatic cancer risk, nor was there any difference in effect estimates between strata of smokers and non-smokers. The results of our current analysis do not support the role of major dietary patterns in the development of pancreatic cancer

Dietary Predictors and Plasma Concentrations of Perfluorinated Compounds in a Coastal Population from Northern Norway

Dietary intake, age, gender, and body mass index were investigated as possible predictors of perfluorinated compounds in a study population from northern Norway (44 women and 16 men). In addition to donating a blood sample, the participants answered a detailed questionnaire about diet and lifestyle. Perfluorooctane sulfonate (PFOS) (29 ng/mL), perfluorooctanoate (PFOA) (3.9 ng/mL), perfluorohexane sulfonate (PFHxS) (0.5 ng/mL), perfluorononanoate (PFNA) (0.8 ng/mL), and perfluoroheptane sulfonate (PFHpS) (1.1 ng/mL) were detected in more than 95% of all samples. Of the dietary items investigated, fruit and vegetables significantly reduced the concentrations of PFOS and PFHpS, whereas fatty fish to a smaller extent significantly increased the levels of the same compounds. Men had significantly higher concentrations of PFOS, PFOA, PFHxS, and PFHpS than women. There were significant differences in PFOS isomer pattern between genders, with women having the largest proportion of linear PFOS. PFOS, PFHxS, and PFHpS concentrations also increased with age

Sex hormones and gene expression signatures in peripheral blood from postmenopausal women - the NOWAC postgenome study

<p>Abstract</p> <p>Background</p> <p>Postmenopausal hormone therapy (HT) influences endogenous hormone concentrations and increases the risk of breast cancer. Gene expression profiling may reveal the mechanisms behind this relationship.</p> <p>Our objective was to explore potential associations between sex hormones and gene expression in whole blood from a population-based, random sample of postmenopausal women</p> <p>Methods</p> <p>Gene expression, as measured by the Applied Biosystems microarray platform, was compared between hormone therapy (HT) users and non-users and between high and low hormone plasma concentrations using both gene-wise analysis and gene set analysis. Gene sets found to be associated with HT use were further analysed for enrichment in functional clusters and network predictions. The gene expression matrix included 285 samples and 16185 probes and was adjusted for significant technical variables.</p> <p>Results</p> <p>Gene-wise analysis revealed several genes significantly associated with different types of HT use. The functional cluster analyses provided limited information on these genes. Gene set analysis revealed 22 gene sets that were enriched between high and low estradiol concentration (HT-users excluded). Among these were seven oestrogen related gene sets, including our gene list associated with systemic estradiol use, which thereby represents a novel oestrogen signature. Seven gene sets were related to immune response. Among the 15 gene sets enriched for progesterone, 11 overlapped with estradiol. No significant gene expression patterns were found for testosterone, follicle stimulating hormone (FSH) or sex hormone binding globulin (SHBG).</p> <p>Conclusions</p> <p>Distinct gene expression patterns associated with sex hormones are detectable in a random group of postmenopausal women, as demonstrated by the finding of a novel oestrogen signature.</p

Plasma 25 hydroxyvitamin D level and blood gene expression profiles: a cross-sectional study of the Norwegian Women and Cancer Post-genome Cohort

Background/Objectives: Vitamin D deficiency has been associated with increased risk of developing several diseases, but much is unknown about the molecular effects involved. Gene expression technology is increasingly being used to elucidate molecular mechanisms related to nutritional factors, and in this study of free-living, middle-aged Norwegian women, we aimed at identifying gene expression pathways in the blood associated with vitamin D status. Subjects/Methods: Blood samples and questionnaires were collected as a part of the Norwegian Women and Cancer Post-genome Cohort (500 invited subjects, 218 included). Plasma 25 hydroxyvitamin D (25(OH)D) concentrations were measured using high-performance liquid chromatography, and we compared groups with sufficient versus deficient vitamin D status (25(OH)D >50 nmol/l (n=66) versus <37.5 nmol/l (n=83)), to identify differences in gene expression profiles obtained using full-genome microarrays. Results: In a targeted pathway-level analysis, several immunological processes, immune cell functions and major signaling pathways were differentially regulated according to vitamin D status (P<0.01). To a certain degree, results from in vitro studies reported in the literature were reflected in this population setting. Conclusions: We conclude that vitamin D status measured as 25(OH)D was associated with molecular pathways that may ultimately affect the potential onset of diseases. The use of gene expression analysis in a population setting may give valuable input to the study of effects of nutritional factors.publishedVersio

Time trends of perfluoroalkyl substances in blood in 30-year old Norwegian men and women in the period 1986–2007

Biomonitoring studies are helpful tools and can increase our knowledge on time trends in human blood concentrations of PFASs: how they relate to emission trends and the potential prenatal exposure for future generations. In this study, serum was sampled in cross-sections of men and women who were 30 years old in each of the years 1986, 1994, 2001, and 2007 in Northern Norway and analyzed for 23 PFASs. Differences in serum concentrations across sampling years were investigated graphically and with significance testing and compared with those observed in our previous longitudinal study using repeated individual measurements in older men in the same years. The results demonstrate overall increasing blood burdens of PFASs in men and women in reproductively active ages during 1986–2001 and decreases until 2007. However, longer chained PFASs were still increasing in 2007 indicating divergent time trends between the different PFASs, underlining the importance of continued biomonitoring. Comparisons between 30-year-old men and older men within the same population demonstrated variation in time trends in the exact same years, underlining that biomonitoring studies must regard historic exposures and birth cohort effects

Pre-diagnostic intake of vitamin D and incidence of colorectal cancer by anatomical subsites: the Norwegian Women and Cancer Cohort Study (NOWAC)

According to the World Cancer Research Fund International, vitamin D might decrease the risk of colorectal cancer (CRC). However, less is known about the association with cancers in different subsites of the colon and in the rectum. The aim of this study was to examine associations between pre-diagnostic intake of vitamin D and risk of CRC by anatomical subsites. Data from 95 416 participants in the Norwegian Women and Cancer Cohort Study was included, and vitamin D intake was estimated from two repeated FFQ. Associations between vitamin D intake and incidence of CRC were assessed using multivariable Cox regression. During follow-up, there were 1774 incident cases of CRC. A small but borderline significant inverse association was found for a 5-µg increase in vitamin D intake and risk of CRC (hazard ratio (HR) = 0·97; 95 % CI 0·93, 1·01) and colon cancer (HR = 0·96; 95 % CI 0·91, 1·01). High (≥ 20 µg) compared with low (< 10 µg) vitamin D intake was associated with 17 % borderline significant reduced risk of CRC (HR = 0·83; 95 % CI 0·68, 1·02). Medium (10–19 µg) v. low intake (< 10 µg) was associated with 27 % reduced risk of proximal colon cancer (HR = 0·73; 95 % CI 0·57, 0·94). No significant associations were observed between vitamin D intake and risk of distal colon or rectal cancer. Our study indicates that vitamin D may be differently associated with subsites of the colon. The association between vitamin D intake and proximal colon cancer is novel

Trajectories of body mass index in adulthood and risk of subtypes of postmenopausal breast cancer

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 (pheterogeneity 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

The burden of colon cancer attributable to modifiable factors—The Norwegian Women and Cancer Study

Colon cancer is the second most frequently diagnosed cancer in women in Norway, where incidence rates of colon cancer increased 3-fold between 1955 and 2014, for unknown reasons. We aimed to assess the burden of colon cancer attributable to modifiable risk factors in Norwegian women using the data from the Norwegian Women and Cancer (NOWAC) study. Self-reported information from 35 525 women from the NOWAC study were available. These included the following exposures: smoking status, alcohol consumption, body mass index, physical activity, intake of calcium, fibers, and red and processed meat. Colon cancer cases were identified from the Cancer Registry of Norway. A parametric piecewise constant hazards model was used to estimate the strength of exposure-cancer associations. Population attributable fractions with 95% confidence intervals (CIs) were calculated considering competing risk of death. The fraction of incident colon cancer attributable to ever smoking was 18.7% (95% CI 4.7%-30.6%), low physical activity 10.8% (95% CI −0.7% to 21.0%), alcohol consumption 14.5% (95% CI −2.8% to 28.9%), and low intake of calcium 10.0% (95% CI −7.8% to 24.8%). A small proportion of colon cancer cases was attributable to combined intake of red and processed meat over 500 g/week, overweight/obesity, and low intake of fibers. Jointly, these seven risk factors could explain 46.0% (95% CI 23.0%-62.4%) of the colon cancer incidence burden. Between 23% and 62% of the colon cancer burden among women in Norway was attributable to modifiable risk factors, indicating an important preventive potential of a healthy lifestyle