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Background A common 30 kb deletion affecting the APOBEC3A and APOBEC3B genes has been linked to increased APOBEC activity and APOBEC-related mutational signatures in human cancers. The role of this deletion as a cancer risk factor remains controversial. Materials and Methods We genotyped the APOBEC3A/B deletion in a sample of 1,470 Norwegian endometrial cancer cases and compared to 1,918 healthy controls. For assessment across Caucasian populations, we mined genotypes of the SNP rs12628403, which is in strong linkage disequilibrium with the deletion, in a GWAS dataset of 4,274 cases and 18,125 healthy controls, through the ECAC consortium. Results We found the APOBEC3A/B deletion variant to be significantly associated with reduced risk of endometrial cancer among Norwegian women (OR = 0.75; 95% CI = 0.62–0.91; p = 0.003; dominant model). Similar results were found in the subgroup of endometrioid endometrial cancer (OR = 0.64; 95% CI = 0.51–0.79; p = 3.6 × 10−5; dominant model). The observed risk reduction was particularly strong among individuals in the range of 50–60 years of age (OR = 0.51; 95% CI = 0.33–0.78; p = 0.002; dominant model). In the different populations included in the ECAC dataset, the ORs varied from 0.85 to 1.05. Although five out of six populations revealed ORs

Supplementary table 1: Overview of the number of cohort studies providing information on each type of risk factor in the pooled data set

Breast cancer is a leading cancer diagnosis among premenopausal women around the world. Unlike rates in postmenopausal women, incidence rates of advanced breast cancer have increased in recent decades for premenopausal women. Progress in identifying contributors to breast cancer risk among premenopausal women has been constrained by the limited numbers of premenopausal breast cancer cases in individual studies and resulting low statistical power to subcategorize exposures or to study specific subtypes. The Premenopausal Breast Cancer Collaborative Group was established to facilitate cohort-based analyses of risk factors for premenopausal breast cancer by pooling individual-level data from studies participating in the United States National Cancer Institute Cohort Consortium. This article describes the Group, including the rationale for its initial aims related to pregnancy, obesity, and physical activity. We also describe the 20 cohort studies with data submitted to the Group by June 2016. The infrastructure developed for this work can be leveraged to support additional investigations. Cancer Epidemiol Biomarkers Prev; 26(9); 1360–9. ©2017 AACR.

Publisher Copyright: © 2022 The Authors. International Journal of Cancer published by John Wiley & Sons Ltd on behalf of UICC. Previous studies had limited power to assess the associations of testosterone with aggressive disease as a primary endpoint. Further, the association of genetically predicted testosterone with aggressive disease is not known. We investigated the associations of calculated free and measured total testosterone and sex hormone-binding globulin (SHBG) with aggressive, overall and early-onset prostate cancer. In blood-based analyses, odds ratios (OR) and 95% confidence intervals (CI) for prostate cancer were estimated using conditional logistic regression from prospective analysis of biomarker concentrations in the Endogenous Hormones, Nutritional Biomarkers and Prostate Cancer Collaborative Group (up to 25 studies, 14 944 cases and 36 752 controls, including 1870 aggressive prostate cancers). In Mendelian randomisation (MR) analyses, using instruments identified using UK Biobank (up to 194 453 men) and outcome data from PRACTICAL (up to 79 148 cases and 61 106 controls, including 15 167 aggressive cancers), ORs were estimated using the inverse-variance weighted method. Free testosterone was associated with aggressive disease in MR analyses (OR per 1 SD = 1.23, 95% CI = 1.08-1.40). In blood-based analyses there was no association with aggressive disease overall, but there was heterogeneity by age at blood collection (OR for men aged

Background: Parity is widely recognized as protective for breast cancer, but breast cancer risk may be increased shortly after childbirth. Whether this risk varies with breastfeeding, family history of breast cancer, or specific tumor subtype has rarely been evaluated. Objective: To characterize breast cancer risk in relation to recent childbirth. Design : Pooled analysis of individual-level data from 15 prospective cohort studies. Setting: The international Premenopausal Breast Cancer Collaborative Group. Participants: Women younger than 55 years. Measurements: During 9.6 million person-years of follow-up, 18 826 incident cases of breast cancer were diagnosed. Hazard ratios (HRs) and 95% CIs for breast cancer were calculated using Cox proportional hazards regression. Results: Compared with nulliparous women, parous women had an HR for breast cancer that peaked about 5 years after birth (HR, 1.80 [95% CI, 1.63 to 1.99]) before decreasing to 0.77 (CI, 0.67 to 0.88) after 34 years. The association crossed over from positive to negative about 24 years after birth. The overall pattern was driven by estrogen receptor (ER)–positive breast cancer; no crossover was seen for ER-negative cancer. Increases in breast cancer risk after childbirth were pronounced when combined with a family history of breast cancer and were greater for women who were older at first birth or who had more births. Breastfeeding did not modify overall risk patterns. Limitations: Breast cancer diagnoses during pregnancy were not uniformly distinguishable from early postpartum diagnoses. Data on human epidermal growth factor receptor 2 (HER2) oncogene overexpression were limited. Conclusion: Compared with nulliparous women, parous women have an increased risk for breast cancer for more than 20 years after childbirth. Health care providers should consider recent childbirth a risk factor for breast cancer in young women. Primary Funding Source: The Avon Foundation, the National Institute of Environmental Health Sciences, Breast Cancer Now and the UK National Health Service, and the Institute of Cancer Research.

Imre Janszky,1 Johan Håkon Bjørngaard,1 Pål Romundstad,1 Lars Vatten,1 Nicola Orsini2 1Deparment of Public Health, Faculty of Medicine and Health, Norwegian University of Science and Technology, Trondheim, Norway; 2Department of Public Health Sciences, Karolinska Insitutet, Stockholm, Sweden Abstract: Currently used methods to express random error are often misinterpreted and consequently misused by biomedical researchers. Previously we proposed a simple approach to quantify the amount of random error in epidemiological studies using OR for binary exposures. Expressing random error with the number of random error units (REU) does not require solid background in statistics for a proper interpretation and cannot be misused for making oversimplistic interpretations relying on statistical significance. We now expand the use of REU to the most common measures of associations in epidemiology and to continuous variables, and we have developed a Stata program, which greatly facilitates the calculation of REU. Keywords: statistical significance, confidence intervals, P Value, random error, random error units

Background While germline CHEK2 mutations have been linked to a moderately elevated cancer risk, to date, a limited number of such mutations have been identified. Recently, we reported a germline nonsense mutation (C283T; R95*), introducing an early stop-codon, in two Norwegian patients diagnosed with locally advanced breast cancer. Both patients were resistant to anthracycline therapy, resembling what has been observed for TP53 mutations. Methods In the present study, we screened a large population based sample, including 3748 non-cancer individuals and 7081 incident cancer cases (breast cancer, n = 1717; prostate cancer n = 2501, lung cancer n = 1331 and colorectal cancer n = 1532), for the distribution of CHEK2 R95*. Results We found that 12 individuals (0.11 %) carried the R95* variant: 4 non-cancer individuals (0.11 %), 4 breast cancer cases (0.23 %), and 4 prostate cancer cases (0.16 %). Although the low number of observations precluded formal statistical assessment, our data may indicate an elevated risk for breast (OR: 2.19, 95 % CI: 0.55–8.75) and prostate cancer (OR: 1.5, 95 % CI: 0.36–6.00) associated with CHEK2 R95*. By mining international databanks, we found no individuals carrying the R95* mutation, indicating it to be restricted to the Norwegian population. Conclusion We provide proof-of-concept that previously unknown CHEK2 germline mutations may be present in certain populations. Notably, germline mutations in tumours are in general missed by contemporary massive parallel sequencing strategies, since tumour mutations are usually filtered against the germline. The fact that the CHEK2 R95* mutation may be associated with resistance to anthracyclines in cancer patients emphasizes its possible clinical importance.

To describe lower urinary tract symptoms, prostate volume and peak urinary flow rate, and investigate the relationships among urological variables in a community sample of Norwegian men.A cross-sectional study of 611 men, aged 55-70 years, who underwent a clinical urological examination including uroflowmetry, residual urine measurement, and transrectal ultrasonography of the prostate. All the men completed a questionnaire which included the International Prostate Symptom Score (IPSS).Severe symptoms were reported by 5%, while 23.6% reported moderate symptoms, and the overall median IPSS was 4 (q1 = 25th percentile, 1; q3 = 75th percentile, 9). The median peak flow rate was 15 ml/s (q1 = 11; q2 = 22) while median prostate volume was 30 cm(3) (q1 = 23; q3 = 38), with little variation evident across the narrow age range of 55-70 years. A positive modest correlation (r = 0.176) was found between IPSS and prostate volume, and a negative correlation between IPSS and peak flow rate (r = -0.278). There was a modest correlation between body mass index (BMI) and prostate size, but no significant correlation between BMI and IPSS.In this population-based study, moderate lower urinary tract symptoms were reported by 24% and severe symptoms by 5% of community men. The distribution of lower urinary tract symptoms, prostate volume and peak urinary flow rate in Norwegian men is comparable to that described in similar studies conducted in Spain, Holland and USA.

The aim of the study was to evaluate the prevalence of overweight and obesity in the population of Świętokrzyskie Province in Poland.Body mass index (BMI), waist to hip ratio (WHR) and waist circumference (WC) in the Polish-Norwegian Study (PONS) was measured in 2,567 females and 1,287 males. Anthropometric measurements included fat mass, height, weight, waist and hip circumference. BMI and WHR were calculated.Data showed that 52% of males and 42% of females were overweight (25.0 ≤ BMI30.0 kg/m2), and the prevalence of obesity (BMI ≥ 30.0 kg/m2) was 35% in both genders. The average BMI was higher in males (28.5 kg/m2) than in females (28.2 kg/m2). Analysis of WC showed that 36% of males and 45% of females had abdominal obesity, whereas measurements of WHR showed abdominal obesity in 64% of males and 79% of females. Generally, the prevalence of obesity was higher in the older age group (55-64 years) and in rural inhabitants. The prevalence of overweight increased with educational level, but the prevalence of obesity decreased with level of education in both males and females.Almost 80% of the PONS population were either overweight or obese; therefore, the PONS population is at increased risk of developing obesity-related diseases.

The aim of this cohort study was to evaluate selected mineral and vitamin intake of the Polish-Norwegian Study (PONS) participants.Daily mineral and vitamin intake of PONS study participants was estimated using Food Frequency Questionnaire (FFQ). Overall, 3,862 inhabitants of Świętokrzyskie Province aged 45-64 (2,572 females and 1,290 males) enrolled in the study.Mean calcium, iron, magnesium, phosphorus, potassium, and sodium intake were, in males: 660.6 mg/day, 15.4 mg/day, 218.5 mg/day, 889.3 mg/day, 2,453.4 mg/day and 2,571.5 mg/day, and in females: 703.6 mg/day, 13.9 mg/day, 220.8 mg/day, 916.3 mg/day, 2,497.3 mg/day and 2,301.8 mg/day, respectively. Iron and sodium intake was significantly higher in males compared to females. Calcium intake was lower in males than in females and in participants aged 55-64 then those aged 45-54. Estimated daily sodium intake was similar among individuals with and without hypertension. Mean vitamin C, thiamin, riboflavin, vitamin B6, A and E were, in males: 80.1 mg/day, 1.3 mg/day, 1.5 mg/day, 1.6 mg/day, 8,454.0 IU/day and 5.4 mg/day and in females: 83.7 mg/day, 1.1 mg/day, 1.6 mg/day, 1.6 mg/day, 9,494.6 IU/day and 4.9 mg/day, respectively. Females had a higher intake of vitamin C and A , while males had higher thiamin and vitamin E intakes. Higher daily vitamin C intake was observed in the younger than in the older group, and in participants with higher education than those with a lower level of education.Significant differences were observed in daily intake of some vitamins and minerals by gender, age, level of education, and place of residence. Some participants had a lower intake of some minerals and vitamins than Polish recommendations.

The aim of this cohort study was to evaluate the prevalence of hypertension and cardiovascular risk factors in the studied population.Presented results are a part of the Polish-Norwegian Study (PONS) project. The study group consisted of 3,862 inhabitants of Świętokrzyskie Province aged 45-64 years (2,572 females and 1,290 males).Prevalence, awareness and control of hypertension was evaluated in the studied population of 3,854 urban and rural inhabitants. Mean blood pressure in the whole studied population was 139.6/81.9 mmHg; of the studied population 61.7% were hypertensive. Hypertension was more prevalent in the studied males (70.63%) than in the females (57.24%). In both males and females, the older subgroups (55-64 y.o.) had significantly higher blood pressure than the younger subgroups (45-54). Education had a significant impact on the prevalence of hypertension, and the highest prevalence of hypertension was observed in the middle level educated groups of females and males. No significant difference was observed between rural and urban inhabitants. In both females and males, the prevalence of hypertension significantly decreased with level of education. Hypertension was well-controlled in only 13.8% of the subjects. More studied females than males achieved good control of blood pressure (14.09 vs. 12.7%), and better control of blood pressure was significantly more frequent in better those who were better educated. Hypertension was not diagnosed in 23.2% of studied population. Significantly, more males than females had undiagnosed hypertension (30.4 vs. 19.5%). No significant difference between rural and urban populations was observed. Interestingly, both in females and males, the better educated groups had more undiagnosed hypertension than those who were well-educated.The studied group had a high prevalence of hypertension (61.7%), which was less frequent and better controlled in the studied females than in the males. No significant difference was observed between the urban and rural populations. Level of education had significant impact on the prevalence of hypertension.

The aim of this study was to assess the dietary intake of participants in the Polish-Norwegian Study (PONS).The presented study comprised 3,862 inhabitants of Świętokrzyskie Province aged 45-64 (2,572 females and 1,290 males). Daily intakes of energy, protein, carbohydrate, fat and fatty acid were estimated using the Food Frequency Questionnaire (FFQ).Energy intake was significantly higher in males than females (1,461.4 vs 1,320.7 kcal/day), and in participants aged 45-54 than in those aged 55-64 (1,409.5 vs 1,338.5 kcal/day). The percentage of energy from saturated fatty acids was higher than dietary recommendations. Protein, fat and carbohydrate intakes were significantly higher in males compared to females, and in younger than in older group. Daily cholesterol intake was significantly higher in males compared to females and in younger than in older group. People with a higher level of education had a higher energy, protein and fat intake.Under-reporting of energy intake was observed in a significant percentage of participants, especially in males. Gender, age and education status had statistically significant impact on dietary intake. Increase in the intake of dietary fibre, mono- and polyunsaturated fatty acids with diet by the studied participants will make the diets more healthy.

The burden of cancer in Eastern Europe is expected to increase, and in 2006, Polish males were ranked second in lifetime risk of lung cancer. The Polish-Norwegian Study (PONS) is a population study in the Kielce District, and the presented study describes the distribution of preventable causes of cancer according to gender, age, education, and urban/rural status.PONS comprises individuals 45-64 years of age at baseline. A structured lifestyle interview was conducted, and the following risk factors were recorded: smoking, alcohol consumption and obesity. Binomial regression analysis was used to estimate age and gender adjusted prevalence ratios (PR) for the associated factors.A total of 3,862 adults were included in the analysis. Approximately 17% reported current tobacco smoking on a daily basis, 34% were former smokers, and 49% were non- smokers. Current smoking was more prevalent in males (20%) than females (15%), but there was no clear association with educational level or urban/rural status. Females also reported a lower frequency of alcohol consumption than males. Among males, 15% reported drinking alcohol more than once a week, as compared to 2% of the females. There was no clear association with urban/rural status, or with level of education. The total prevalence of obesity (BMI ≥ 30) was 30%; the prevalence of obesity class 2 (BMI ≥ 35) and class 3 (BMI ≥ 40) was 8% and 1.7%, respectively. Obesity increased by age, especially in females, and was less frequent among people with high education and people with urban residence.The Kielce region of Poland is experiencing a significant burden of cancer risk factors, including obesity and tobacco smoking, but smoking may be a decreasing habit. It is necessary to increase the awareness of the population to the harmful eff ects of smoking and obesity to prevent cancer and other lifestyle related diseases.

In Central and Eastern European countries, cardiovascular disorders (CVD) in middle age are much more common than in Western Europe, and it is imperative to understand the causes underlying this excess disease burden. The metabolic syndrome comprises a constellation of metabolic abnormalities that increase the risk of cardiovascular disease.Data were obtained by structured interview, and by measurements of anthropometric factors and blood analyses among 3,862 individuals. Metabolic syndrome was defined according the International Diabetes Federation Task Force on Epidemiology and Prevention, as the presence of at least 3 of 5 abnormalities: 1) abdominal obesity, 2) glucose intolerance, 3) high triglycerides, 4) low HDL cholesterol, 5) high blood pressure.Overall, 1,518 participants (39.5%) had metabolic syndrome. The prevalence among females was 34.3% (877 females) vs. 49.9% (641 males) among males, and increased with age in both genders. Abdominal obesity was the most common abnormality (2,897 participants, 75.1%), followed by high blood pressure (2,741 participants, 71%), glucose intolerance (1,437 participants, 37.3%), elevated triglycerides (817 participants, 21.2%) and low HDL (615 participants, 15.9%).The prevalence of metabolic syndrome and metabolic abnormalities is high and represents strong risk factors for CVD morbidity and mortality. However, these factors are all potentially preventable by lifestyle modification and/or by pharmacological treatment. There is an urgent need for the health service to act, and to increase public awareness of metabolic syndrome.

To investigate whether maternal caffeine consumption is associated with increased maternal homocysteine (Hcy) levels in uncomplicated pregnancies.Ninety-two pregnant women were randomly selected, and maternal serum levels of folate, vitamin B(12), and Hcy at gestational weeks 17 and 33 were measured. Caffeine consumption was estimated from dietary records collected at the same gestational ages.In women who smoked, Hcy levels were associated with caffeine consumption both in gestational weeks 17 and 33 and with folate at week 33. Consumption of one cup of coffee was associated with an increase in maternal Hcy of 0.26 micromol/l at week 17 and 0.69 micromol/l at week 33, indicating that one extra cup (150 ml) of coffee per day may increase Hcy by 5--10% in pregnant smokers. In non-smokers, caffeine consumption was not associated with Hcy levels.In uncomplicated pregnancies, maternal caffeine consumption early in the second and in the third trimester is associated with increased maternal Hcy levels in women who smoked, but not in non-smokers.

To examine changes in temporal trends in breast cancer mortality in women living in 30 European countries.Retrospective trend analysis. Data source WHO mortality database on causes of deaths Subjects reviewed Female deaths from breast cancer from 1989 to 2006Changes in breast cancer mortality for all women and by age group (50, 50-69, andor=70 years) calculated from linear regressions of log transformed, age adjusted death rates. Joinpoint analysis was used to identify the year when trends in all age mortality began to change.From 1989 to 2006, there was a median reduction in breast cancer mortality of 19%, ranging from a 45% reduction in Iceland to a 17% increase in Romania. Breast cancer mortality decreased byor=20% in 15 countries, and the reduction tended to be greater in countries with higher mortality in 1987-9. England and Wales, Northern Ireland, and Scotland had the second, third, and fourth largest decreases of 35%, 29%, and 30%, respectively. In France, Finland, and Sweden, mortality decreased by 11%, 12%, and 16%, respectively. In central European countries mortality did not decline or even increased during the period. Downward mortality trends usually started between 1988 and 1996, and the persistent reduction from 1999 to 2006 indicates that these trends may continue. The median changes in the age groups were -37% (range -76% to -14%) in women aged50, -21% (-40% to 14%) in 50-69 year olds, and -2% (-42% to 80%) inor=70 year olds.Changes in breast cancer mortality after 1988 varied widely between European countries, and the UK is among the countries with the largest reductions. Women aged50 years showed the greatest reductions in mortality, also in countries where screening at that age is uncommon. The increasing mortality in some central European countries reflects avoidable mortality.