Relationship Between Hepatitis C Infection and Treatment Status and Coronavirus Disease 2019-Related Hospitalizations in Georgia.

BACKGROUND: The aim of this study was to evaluate the impact of hepatitis C virus (HCV) infection and treatment status on coronavirus disease 2019 (COVID-19)-related hospitalizations in Georgia. METHODS: We analyzed 2020-2021 Georgian health registry data for COVID-19-positive individuals and categorized the data by HCV infection and treatment status. Logistic regression was used to assess the strengths of the associations. RESULTS: Treated individuals with HCV had lower odds of COVID-19-related hospitalization compared to anti-HCV-negative individuals, while untreated HCV-viremic and anti-HCV-positive nonviremic individuals had higher odds. CONCLUSIONS: HCV treatment prior to COVID-19 infection was associated with lower odds of COVID-19-related hospitalization, highlighting the benefits of HCV management in the context of the pandemic.

SARS-CoV-2 infection during pregnancy and the risk of adverse maternal outcomes in the Republic of Georgia: a national birth registry-based cohort study.

BACKGROUND: Georgia experienced an increase in maternal deaths (MD) during the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic, which warrants further investigation. This study aimed to assess associations between timing of SARS-CoV-2 infection during pregnancy and MD, post-delivery intensive care unit (ICU) admission, and caesarean section (CS) delivery. METHODS: We performed a national birth registry-based cohort study of pregnant women who had completed 22 weeks of gestation and delivered between February 28, 2020, and August 31, 2022. The data were linked to coronavirus disease 2019 (COVID-19) testing, vital, and immunization registries. Pregnant women were classified into three groups: confirmed SARS-CoV-2 infection from conception through 31 days before delivery; confirmed infection within 30 days before or at delivery; and women negative for SARS-CoV-2 infection or without any test results (reference group). Multivariable logistic regression was used to calculate the adjusted odds ratios (aORs) and 95% confidence intervals (CIs). RESULTS: Among 111,493 pregnant women, 16,751 had confirmed infection during pregnancy, and 7,332 were fully vaccinated against COVID-19 before delivery. Compared to the reference group, those with confirmed infection within 30 days before or at delivery experienced increased odds of MD (aOR: 43.11, 95% CI, 21.99-84.55), post-delivery ICU admission (aOR: 5.20, 95% CI, 4.05-6.67), and CS delivery (aOR: 1.11, 95% CI, 1.03-1.20). CONCLUSIONS: Pregnant women in Georgia with confirmed SARS-CoV-2 infection within 30 days before or at delivery experienced a considerably higher risk of MD and post-delivery ICU admission and a slightly higher risk for CS delivery. Additionally, the results highlighted that most pregnant women were not vaccinated against COVID-19. These findings should alert stakeholders that adherence to public health preventive measures needs to be improved.

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.

Body shape phenotypes of multiple anthropometric traits and cancer risk: a multi-national cohort study.

BACKGROUND: Classical anthropometric traits may fail to fully represent the relationship of weight, adiposity, and height with cancer risk. We investigated the associations of body shape phenotypes with the risk of overall and site-specific cancers. METHODS: We derived four distinct body shape phenotypes from principal component (PC) analysis on height, weight, body mass index (BMI), waist (WC) and hip circumferences (HC), and waist-to-hip ratio (WHR). The study included 340,152 men and women from 9 European countries, aged mostly 35-65 years at recruitment (1990-2000) in the European Prospective Investigation into Cancer and Nutrition (EPIC) study. Cox proportional hazards regression was used to estimate multivariable-adjusted hazard ratios (HRs) and 95% confidence intervals (CIs). RESULTS: After a median follow-up of 15.3 years, 47,110 incident cancer cases were recorded. PC1 (overall adiposity) was positively associated with the risk of overall cancer, with a HR per 1 standard deviation (SD) increment equal to 1.07 (95% confidence interval 1.05 to 1.08). Positive associations were observed with 10 cancer types, with HRs (per 1 SD) ranging from 1.36 (1.30-1.42) for endometrial cancer to 1.08 (1.03-1.13) for rectal cancer. PC2 (tall stature with low WHR) was positively associated with the risk of overall cancer (1.03; 1.02-1.04) and five cancer types which were not associated with PC1. PC3 (tall stature with high WHR) was positively associated with the risk of overall cancer (1.04; 1.03-1.05) and 12 cancer types. PC4 (high BMI and weight with low WC and HC) was not associated with overall risk of cancer (1.00; 0.99-1.01). CONCLUSIONS: In this multi-national study, distinct body shape phenotypes were positively associated with the incidence of 17 different cancers and overall cancer.

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.

Fluorine Mass Balance, including Total Fluorine, Extractable Organic Fluorine, Oxidizable Precursors, and Target Per- and Polyfluoroalkyl Substances, in Pooled Human Serum from the Tromsø Population in 1986, 2007, and 2015.

Of the thousands of per- and polyfluoroalkyl substances (PFAS) known to exist, only a small fraction (≤1%) are commonly monitored in humans. This discrepancy has led to concerns that human exposure may be underestimated. Here, we address this problem by applying a comprehensive fluorine mass balance (FMB) approach, including total fluorine (TF), extractable organic fluorine (EOF), total oxidizable precursors (TOP), and selected target PFAS, to human serum samples collected over a period of 28 years (1986, 2007, and 2015) in Tromsø, Norway. While concentrations of TF did not change between sampling years, EOF was significantly higher in 1986 compared to 2007 and 2015. The ∑12PFAS concentrations were highest in 2007 compared to 1986 and 2015, and unidentified EOF (UEOF) decreased from 1986 (46%) to 2007 (10%) and then increased in 2015 (37%). While TF and EOF were not influenced by sex, women had higher UEOF compared to men, opposite to target PFAS. This is the first FMB in human serum to include TOP, and it suggests that precursors with >4 perfluorinated carbon atoms make a minor contribution to EOF (0-4%). Additional tools are therefore needed to identify substances contributing to the UEOF in human serum.

The association between body fatness and mortality among breast cancer survivors: results from a prospective cohort study.

Evidence linking body fatness to breast cancer (BC) prognosis is limited. While it seems that excess adiposity is associated with poorer BC survival, there is uncertainty over whether weight changes reduce mortality. This study aimed to assess the association between body fatness and weight changes pre- and postdiagnosis and overall mortality and BC-specific mortality among BC survivors. Our study included 13,624 BC survivors from the European Prospective Investigation into Cancer and Nutrition (EPIC) study, with a mean follow-up of 8.6 years after diagnosis. Anthropometric data were obtained at recruitment for all cases and at a second assessment during follow-up for a subsample. We measured general obesity using the body mass index (BMI), whereas waist circumference and A Body Shape Index were used as measures of abdominal obesity. The annual weight change was calculated for cases with two weight assessments. The association with overall mortality and BC-specific mortality were based on a multivariable Cox and Fine and Gray models, respectively. We performed Mendelian randomization (MR) analysis to investigate the potential causal association. Five-unit higher BMI prediagnosis was associated with a 10% (95% confidence interval: 5-15%) increase in overall mortality and 7% (0-15%) increase in dying from BC. Women with abdominal obesity demonstrated a 23% (11-37%) increase in overall mortality, independent of the association of BMI. Results related to weight change postdiagnosis suggested a U-shaped relationship with BC-specific mortality, with higher risk associated with losing weight or gaining > 2% of the weight annually. MR analyses were consistent with the identified associations. Our results support the detrimental association of excess body fatness on the survival of women with BC. Substantial weight changes postdiagnosis may be associated with poorer survival.

The impact of COVID-19-related restrictions on pregnancy and abortion rates in the Republic of Georgia.

BACKGROUND: The Republic of Georgia implemented COVID-19-related restrictions starting on 31 March 2020, when it imposed a 1-month strict lockdown, after which the country continued with some form of restrictions for 1 year. These restrictions created barriers to healthcare access, affected healthcare services, caused severe economic degradation, and changed reproductive behavior. The aim of this study was to explore the impact of COVID-19-related restrictions on pregnancy and abortion rates in Georgia. METHODS: Information on pregnancy, abortion, and related variables was extracted from the Georgian Birth Registry from January 2018 through April 2022. The final study sample included 232,594 pregnancies and 86,729 abortions. We used interrupted time series analysis to study the impact of COVID-19-related restrictions. RESULTS: There were slightly decreasing trends in pregnancy and abortion rates in the pre-pandemic period (1 January 2018-31 March 2020). During the 1-month strict lockdown (1 April-30 April 2020), pregnancy and abortion rates decreased in all investigated age groups. There were no substantial differences in pregnancy or abortion rates in the pandemic period (for pregnancies: 1 April 2020-30 June 2021; for abortions: 1 April 2020-30 April 2022) compared to the pre-pandemic period. The precision of all estimates suggested that both small increases and decreases in pregnancy and abortion rates are reasonably compatible with our data. CONCLUSIONS: Despite the 1-year-long COVID-19-related restrictions, our results did not indicate substantial long-term changes in pregnancy or abortion rates during the study period for any age group. This may indicate that the restrictions did not substantially influence access to contraception, abortion services, or reproductive behavior.

Longitudinal changes in concentrations of persistent organic pollutants (1986-2016) and their associations with type 2 diabetes mellitus.

BACKGROUND: Positive associations have been reported between persistent organic pollutants (POPs) and type 2 diabetes mellitus (T2DM); however, causality has not been established. Over the last decades, environmental exposure to legacy POPs has decreased, complicating epidemiological studies. In addition, physiological risk factors for T2DM may also influence POP concentrations, contributing to a complex network of factors that could impact associations with T2DM. Longitudinal studies on this topic are lacking, and few have assessed prospective and cross-sectional associations between repeated POP measurements and T2DM in the same individuals, which may shed light on causality. OBJECTIVES: To compare longitudinal trends in concentrations of polychlorinated biphenyls (PCBs) and organochlorine pesticides (OCPs) in T2DM cases and controls, and to examine prospective and cross-sectional associations between PCBs, OCPs and T2DM at different time-points before and after T2DM diagnosis in cases. METHODS: We conducted a longitudinal, nested case-control study (1986-2016) of 116 T2DM cases and 139 controls from the Tromsø Study. All participants had three blood samples collected before T2DM diagnosis in cases, and up to two samples thereafter. We used linear mixed-effect models to assess temporal changes of POPs within and between T2DM cases and controls, and logistic regression models to investigate the associations between different POPs and T2DM at different time-points. RESULTS: PCBs, trans-nonachlor, cis-nonachlor, oxychlordane, cis-heptachlor epoxide, p,p'-DDE, and p,p'-DDT declined more slowly in cases than controls, whereas ß-HCH and HCB declined similarly in both groups. Most POPs showed positive associations between both pre- and post-diagnostic concentrations and T2DM, though effect estimates were imprecise. These associations were most consistent for cis-heptachlor epoxide. DISCUSSION: The observed positive associations between certain POPs and T2DM may be because of higher POP concentrations within prospective T2DM cases, due to slower temporal declines as compared to controls.

Association between anthropometry and lifestyle factors and risk of B-cell lymphoma: An exposome-wide analysis.

To better understand the role of individual and lifestyle factors in human disease, an exposome-wide association study was performed to investigate within a single-study anthropometry measures and lifestyle factors previously associated with B-cell lymphoma (BCL). Within the European Prospective Investigation into Cancer and nutrition study, 2402 incident BCL cases were diagnosed from 475 426 participants that were followed-up on average 14 years. Standard and penalized Cox regression models as well as principal component analysis (PCA) were used to evaluate 84 exposures in relation to BCL risk. Standard and penalized Cox regression models showed a positive association between anthropometric measures and BCL and multiple myeloma/plasma cell neoplasm (MM). The penalized Cox models additionally showed the association between several exposures from categories of physical activity, smoking status, medical history, socioeconomic position, diet and BCL and/or the subtypes. PCAs confirmed the individual associations but also showed additional observations. The PC5 including anthropometry, was positively associated with BCL, diffuse large B-cell lymphoma (DLBCL) and MM. There was a significant positive association between consumption of sugar and confectionary (PC11) and follicular lymphoma risk, and an inverse association between fish and shellfish and Vitamin D (PC15) and DLBCL risk. The PC1 including features of the Mediterranean diet and diet with lower inflammatory score showed an inverse association with BCL risk, while the PC7, including dairy, was positively associated with BCL and DLBCL risk. Physical activity (PC10) was positively associated with DLBCL risk among women. This study provided informative insights on the etiology of BCL.

Weight change in middle adulthood and risk of cancer in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort.

Obesity is a risk factor for several major cancers. Associations of weight change in middle adulthood with cancer risk, however, are less clear. We examined the association of change in weight and body mass index (BMI) category during middle adulthood with 42 cancers, using multivariable Cox proportional hazards models in the European Prospective Investigation into Cancer and Nutrition cohort. Of 241 323 participants (31% men), 20% lost and 32% gained weight (>0.4 to 5.0 kg/year) during 6.9 years (average). During 8.0 years of follow-up after the second weight assessment, 20 960 incident cancers were ascertained. Independent of baseline BMI, weight gain (per one kg/year increment) was positively associated with cancer of the corpus uteri (hazard ratio [HR] = 1.14; 95% confidence interval: 1.05-1.23). Compared to stable weight (±0.4 kg/year), weight gain (>0.4 to 5.0 kg/year) was positively associated with cancers of the gallbladder and bile ducts (HR = 1.41; 1.01-1.96), postmenopausal breast (HR = 1.08; 1.00-1.16) and thyroid (HR = 1.40; 1.04-1.90). Compared to maintaining normal weight, maintaining overweight or obese BMI (World Health Organisation categories) was positively associated with most obesity-related cancers. Compared to maintaining the baseline BMI category, weight gain to a higher BMI category was positively associated with cancers of the postmenopausal breast (HR = 1.19; 1.06-1.33), ovary (HR = 1.40; 1.04-1.91), corpus uteri (HR = 1.42; 1.06-1.91), kidney (HR = 1.80; 1.20-2.68) and pancreas in men (HR = 1.81; 1.11-2.95). Losing weight to a lower BMI category, however, was inversely associated with cancers of the corpus uteri (HR = 0.40; 0.23-0.69) and colon (HR = 0.69; 0.52-0.92). Our findings support avoiding weight gain and encouraging weight loss in middle adulthood.

Pre- and post-diagnostic blood profiles of chlorinated persistent organic pollutants and metabolic markers in type 2 diabetes mellitus cases and controls; a pilot study.

OBJECTIVE: Several risk factors for type 2 diabetes mellitus (T2DM) are also associated with blood concentrations of persistent organic pollutants (POPs), and factors related to the disease may affect POP concentrations, and subsequent associations between POPs and T2DM. The purpose of this pilot study was to investigate the change in concentrations of lipids, hormones and POPs pre- and post-diagnosis in T2DM cases compared to healthy controls and their associations with T2DM. METHODS: We measured POPs, lipids, and thyroid and steroid hormones in plasma from 44 female cases collected prior to (pre-diagnostic) and following (post-diagnostic) T2DM diagnosis, and in 44 healthy female age-matched controls. We compared cross-sectional differences and longitudinal changes within and between matched cases and controls with t-tests and multivariable linear regression models. Associations between POP concentrations and T2DM were investigated using conditional logistic regression. RESULTS: Between the pre- and post-diagnostic measurement, cases developed more favorable lipid profiles and the longitudinal changes in lipid-normalized concentrations of non-dioxin-like polychlorinated biphenyls (PCBs), dioxin-like PCBs, beta-hexachlorocyclohexane (HCH), HCB, and 1,1,1-trichloro-2,2-bis(4-chlorophenyl) ethane (p,p'-DDE) differed significantly between cases and controls. The longitudinal changes in POPs were mainly driven by changes in bodyweight, total lipids and T2DM status. Cases had significantly higher pre-diagnostic concentrations of POPs and triglycerides, and lower concentrations of high-density lipoprotein cholesterol and free thyroxin than controls. Pre-diagnostic POP concentrations were not significantly associated with incident T2DM, whereas several post-diagnostic POP concentrations were significantly positively associated with prevalent T2DM. CONCLUSIONS: This pilot study suggests that factors related to T2DM affect blood concentrations of POPs and may partly explain the positive associations between POPs and T2DM.

Anthropometric and reproductive factors and risk of esophageal and gastric cancer by subtype and subsite: Results from the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort.

Obesity has been associated with upper gastrointestinal cancers; however, there are limited prospective data on associations by subtype/subsite. Obesity can impact hormonal factors, which have been hypothesized to play a role in these cancers. We investigated anthropometric and reproductive factors in relation to esophageal and gastric cancer by subtype and subsite for 476,160 participants from the European Prospective Investigation into Cancer and Nutrition cohort. Multivariable hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated using Cox models. During a mean follow-up of 14 years, 220 esophageal adenocarcinomas (EA), 195 esophageal squamous cell carcinomas, 243 gastric cardia (GC) and 373 gastric noncardia (GNC) cancers were diagnosed. Body mass index (BMI) was associated with EA in men (BMI ≥30 vs. 18.5-25 kg/m2 : HR = 1.94, 95% CI: 1.25-3.03) and women (HR = 2.66, 95% CI: 1.15-6.19); however, adjustment for waist-to-hip ratio (WHR) attenuated these associations. After mutual adjustment for BMI and HC, respectively, WHR and waist circumference (WC) were associated with EA in men (HR = 3.47, 95% CI: 1.99-6.06 for WHR >0.96 vs. <0.91; HR = 2.67, 95% CI: 1.52-4.72 for WC >98 vs. <90 cm) and women (HR = 4.40, 95% CI: 1.35-14.33 for WHR >0.82 vs. <0.76; HR = 5.67, 95% CI: 1.76-18.26 for WC >84 vs. <74 cm). WHR was also positively associated with GC in women, and WC was positively associated with GC in men. Inverse associations were observed between parity and EA (HR = 0.38, 95% CI: 0.14-0.99; >2 vs. 0) and age at first pregnancy and GNC (HR = 0.54, 95% CI: 0.32-0.91; >26 vs. <22 years); whereas bilateral ovariectomy was positively associated with GNC (HR = 1.87, 95% CI: 1.04-3.36). These findings support a role for hormonal pathways in upper gastrointestinal cancers.

Healthy lifestyle and the risk of pancreatic cancer in the EPIC study.

Pancreatic cancer (PC) is a highly fatal cancer with currently limited opportunities for early detection and effective treatment. Modifiable factors may offer pathways for primary prevention. In this study, the association between the Healthy Lifestyle Index (HLI) and PC risk was examined. Within the European Prospective Investigation into Cancer and Nutrition cohort, 1113 incident PC (57% women) were diagnosed from 400,577 participants followed-up for 15 years (median). HLI scores combined smoking, alcohol intake, dietary exposure, physical activity and, in turn, overall and central adiposity using BMI (HLIBMI) and waist-to-hip ratio (WHR, HLIWHR), respectively. High values of HLI indicate adherence to healthy behaviors. Cox proportional hazard models with age as primary time variable were used to estimate PC hazard ratios (HR) and 95% confidence intervals (CI). Sensitivity analyses were performed by excluding, in turn, each factor from the HLI score. Population attributable fractions (PAF) were estimated assuming participants' shift to healthier lifestyles. The HRs for a one-standard deviation increment of HLIBMI and HLIWHR were 0.84 (95% CI: 0.79, 0.89; ptrend = 4.3e-09) and 0.77 (0.72, 0.82; ptrend = 1.7e-15), respectively. Exclusions of smoking from HLIWHR resulted in HRs of 0.88 (0.82, 0.94; ptrend = 4.9e-04). The overall PAF estimate was 19% (95% CI: 11%, 26%), and 14% (6%, 21%) when smoking was removed from the score. Adherence to a healthy lifestyle was inversely associated with PC risk, beyond the beneficial role of smoking avoidance. Public health measures targeting compliance with healthy lifestyles may have an impact on PC incidence.

Time trends of persistent organic pollutants in 30 year olds sampled in 1986, 1994, 2001 and 2007 in Northern Norway: Measurements, mechanistic modeling and a comparison of study designs.

BACKGROUND: Human biomonitoring studies have demonstrated decreasing concentrations of many persistent organic pollutants (POPs) in years after emission peaks. OBJECTIVES: To describe time trends of POPs in blood using four cross-sectional samples of 30 year olds from Tromsø, Norway across 1986-2007, and to compare the measured concentrations of polychlorinated biphenyl 153 (PCB-153) to model-estimated values. A second objective was to compare the repeated cross-sectional time trends with those observed in our previous longitudinal study using repeated individual measurements in older men from the same surveys. METHODS: Serum from 45 persons aged 30 years in each of the following years: 1986, 1994, 2001, and 2007 was analyzed for 14 POPs. Further, predicted concentrations of PCB-153 in each sampling year were derived using the emission-based CoZMoMAN model. RESULTS: The median decreases in summed serum POP concentrations (lipid-adjusted) in 1994, 2001, and 2007 relative to 1986 were - 71%, - 81%, and - 86% for women and - 65%, - 77%, and - 87% for men, respectively. The overall time trend in predicted PCB-153 concentrations demonstrated agreement with the observed trend although model predictions were higher than the measured concentrations at all time points. Compared to our previous longitudinal study of repeated individual measurements in older men, similar although more prominent declines were observed in the younger cross-sectional samples. DISCUSSION: Observed declines in serum concentrations from 1986 to 2007 were substantial for legacy POPs in men and women at reproductive ages in Northern Norway and are generally consistent with previous longitudinal biomonitoring efforts in the study population. The measured concentrations and observed declines likely reflect a combination of recent and historic exposures. Small differences in time trends observed between the studies could be attributed to different study designs (i.e. the chosen age group or sex and cross-sectional versus repeated individual measurement sampling).

Methodological issues in a prospective study on plasma concentrations of persistent organic pollutants and pancreatic cancer risk within the EPIC cohort.

BACKGROUND: The use of biomarkers of environmental exposure to explore new risk factors for pancreatic cancer presents clinical, logistic, and methodological challenges that are also relevant in research on other complex diseases. OBJECTIVES: First, to summarize the main design features of a prospective case-control study -nested within the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort- on plasma concentrations of persistent organic pollutants (POPs) and pancreatic cancer risk. And second, to assess the main methodological challenges posed by associations among characteristics and habits of study participants, fasting status, time from blood draw to cancer diagnosis, disease progression bias, basis of cancer diagnosis, and plasma concentrations of lipids and POPs. Results from etiologic analyses on POPs and pancreatic cancer risk, and other analyses, will be reported in future articles. METHODS: Study subjects were 1533 participants (513 cases and 1020 controls matched by study centre, sex, age at blood collection, date and time of blood collection, and fasting status) enrolled between 1992 and 2000. Plasma concentrations of 22 POPs were measured by gas chromatography - triple quadrupole mass spectrometry (GC-MS/MS). To estimate the magnitude of the associations we calculated multivariate-adjusted odds ratios by unconditional logistic regression, and adjusted geometric means by General Linear Regression Models. RESULTS: There were differences among countries in subjects' characteristics (as age, gender, smoking, lipid and POP concentrations), and in study characteristics (as time from blood collection to index date, year of last follow-up, length of follow-up, basis of cancer diagnosis, and fasting status). Adjusting for centre and time of blood collection, no factors were significantly associated with fasting status. Plasma concentrations of lipids were related to age, body mass index, fasting, country, and smoking. We detected and quantified 16 of the 22 POPs in more than 90% of individuals. All 22 POPs were detected in some participants, and the smallest number of POPs detected in one person was 15 (median, 19) with few differences by country. The highest concentrations were found for p,p'-DDE, PCBs 153 and 180 (median concentration: 3371, 1023, and 810 pg/mL, respectively). We assessed the possible occurrence of disease progression bias (DPB) in eight situations defined by lipid and POP measurements, on one hand, and by four factors: interval from blood draw to index date, tumour subsite, tumour stage, and grade of differentiation, on the other. In seven of the eight situations results supported the absence of DPB. CONCLUSIONS: The coexistence of differences across study centres in some design features and participant characteristics is of relevance to other multicentre studies. Relationships among subjects' characteristics and among such characteristics and design features may play important roles in the forthcoming analyses on the association between plasma concentrations of POPs and pancreatic cancer risk.

Use of skincare products and risk of cancer of the breast and endometrium: a prospective cohort study.

BACKGROUND: Concerns have been raised that extensive use of personal care products that contain endocrine disrupting compounds increase the risk of hormone sensitive cancers. OBJECTIVE: To assess the effect of skincare product use on the risk of pre- and postmenopausal breast cancer, estrogen receptor positive (ER+) and negative (ER-) breast cancer and cancer of the endometrium. METHODS: We used data from 106,978 participants in the population-based Norwegian Women and Cancer cohort. Participants were categorized into non-, light, moderate, frequent and heavy users of skincare products based on self-reported use of hand and facial cream and body lotion. Cancer incidence information from the Cancer Registry of Norway was linked to individual data through the unique identity number of Norwegian citizens. Multivariable Cox proportional hazard regression was used to assess the effect of skincare product use on the risk of cancer of the breast and endometrium. We used multiple imputation by chained equations to evaluate the effect of missing data on observed associations. RESULTS: We found no associations between use of skincare products and incidence of premenopausal breast cancer (frequent/heavy versus non-/light use: hazard ratio [HR] =1.10, 95% confidence interval [CI]: 0.92-1.32), postmenopausal breast cancer (heavy versus light use: HR = 0.87, 95% CI: 0.65-1.18, frequent versus light use: HR = 0.97, 95% CI: 0.88, 1.07) or endometrial cancer (frequent/heavy versus non-/light use: HR = 0.97, 95% CI: 0.79-1.20). Use of skincare products did not increase the risk of ER+ or ER- breast cancer and there was no difference in effect across ER status (0.58 ≤ pheterogeneity ≤ 0.99). The magnitude and direction of the effect estimates based on complete case analyses and multiple imputation were similar. CONCLUSION: Heavy use of skincare products, i.e. creaming the body up to two times per day during mid-life, did not increase the risk of cancer of the breast or endometrium.

Dietary patterns of adults and their associations with Sami ethnicity, sociodemographic factors, and lifestyle factors in a rural multiethnic population of northern Norway - the SAMINOR 2 clinical survey.

BACKGROUND: Few population-based studies have assessed dietary behaviors in the rural multiethnic population of Northern Norway. The present study determined dietary patterns and investigated their association with Sami ethnicity, sociodemographic factors, and lifestyle factors in a multiethnic population in rural Northern Norway. METHODS: This cross-sectional study included 4504 participants of the SAMINOR 2 Clinical Survey (2012-2014) aged 40-69 years. All participants completed a lifestyle and food frequency questionnaire. Dietary patterns were determined using principal component analysis. Associations between food patterns and ethnicity, sociodemographic factors, and lifestyle factors were examined by multiple linear regression. RESULTS: Six dietary patterns were identified that accounted for 28% of the variability in food intake in the study sample: 'processed meat/westernized', 'fish/traditional', 'fruit/vegetables', 'reindeer/traditional', 'bread and sandwich spreads', and 'sweets and bakery goods'. The 'reindeer/traditional' pattern was most common among the inland Sami population. The 'fish/traditional' pattern was most common among costal multiethnic Sami and least common among inland Sami and among women independent of ethnicity. The 'fish/traditional' pattern was also positively associated with older age, high education level, small household size, and smoking. Adherence to the 'processed meat/westernized' pattern was lower among inland Sami than inland/coastal non-Sami; no ethnic differences in adherence to this pattern were found between costal multiethnic Sami and inland/coastal non-Sami. Unhealthy lifestyle factors, like low physical activity level and smoking, and younger age were mainly associated with the 'processed meat/westernized' pattern, whereas socioeconomic factors like low education, low gross annual household income, and large household size were related to the 'sweets and bakery goods' pattern. Male gender, low education level, and smoking were associated with the 'bread and sandwich spreads' pattern. The 'fruit/vegetables' pattern was characterized by healthy dietary choices and a health-conscious lifestyle, and was more common in women with a high education level and income. CONCLUSIONS: Adherence to the six identified dietary patterns was characterized by different sociodemographic and lifestyle factors. Ethnicity, in combination with geographical region of residence, was associated with dietary behaviors. This study provides knowledge that will be useful in future studies on dietary patterns related to chronic diseases in the rural population of Northern Norway.

Progestin-only and combined oral contraceptives and receptor-defined premenopausal breast cancer risk: The Norwegian Women and Cancer Study.

Receptor-defined subtypes of breast cancer represent distinct cancer types and have differences in risk factors. Whether the two main hormonal forms of oral contraceptives (OCs); i.e. progestin-only (POC) and combined oral contraceptives (COC), are differentially associated with these subtypes are not well known. The aim of our study was to assess the effect of POC and COC use on hormone receptor-defined breast cancer risk in premenopausal women in a prospective population-based cohort - The Norwegian Women and Cancer Study (NOWAC). Information on OC use was collected from 74,862 premenopausal women at baseline. Updated information was applied when follow-up information became available. Multiple imputation was performed to handle missing data, and multivariable Cox regression models were used to calculate hazard ratios (HR) for breast cancer. 1,245 incident invasive breast cancer cases occurred. POC use ≥5 years was associated with ER+ (HR = 1.59, 95% CI 1.09- 2.32, ptrend = 0.03) and ER+/PR+ cancer (HR = 1.63, 95% CI 1.07-2.48, ptrend = 0.05), and was not associated with ER- (pheterogeneity = 0.36) or ER-/PR- (pheterogeneity = 0.49) cancer. COC use was associated with ER- and ER-/PR- cancer, but did not increase risk of ER+ and ER+/PR+ cancer. Current COC use gave different estimates for ER/PR-defined subtypes (pheterogeneity = 0.04). This is the first study to show significant associations between POC use and hormone receptor-positive breast cancer. The lack of power to distinguish effects of POC use on subtype development calls for the need of larger studies to confirm our finding.