Physical activity and risk of cancer : a population based cohort study including prostate, testicular, colorectal, lung and breast cancer

The overall aim of this thesis was to elucidate any association between physical activity and the subsequent risk of some major types of cancer in the general adult population of Norway: prostate, testicular, colorectal, lung and breast cancer. • Another aim was to examine whether physical activity at work had a different association to these cancer types than physical activity in leisure time. • To investigate whether age, sex. body mass index and hormonal status (pre- and postmenopausal), on one side, and lifestyle-related factors such as smoking and dietary factors, on the other, strengthen or reduce these observed associations. • Could repeated assessments of physical activity induce stronger or weaker risk estimates? • If any associations between physical activity and risk of cancer were observed, then these associations were investigated to ascertain if these could indicate a causal relationship. • To study if changes in physical activity or sustained physical activity inlluence metabolic profiles to any large extent, which would support physical activity as a potent biological mediator of importance in reduction of risk for chronic diseases, e.g. cancer

Blood pressure, cardiorespiratory fitness and body mass : results from the Tromsø activity study

<em><strong>Aims:</strong></em> Modifiable lifestyle factors, as cardiorespiratory fitness (CRF) and body mass, may prevent hypertension.<br />However, it remains unclear whether blood pressure is associated with CRF, independently of body mass index (BMI). Thus, the purpose was to study the relationship between CRF, body composition and blood pressure among 40-44 year old men and women.<br /><em><strong>Methods</strong></em>: During 2007-2008, 12,900 men and women aged 30-85 years attended the sixth survey of the Tromsø study. Blood pressure (mm Hg), height (cm) and weight (kg) were measured and body mass index (BMI kg/m2) was estimated. In a sub-study, the Tromsø Activity Study, CRF [VO2max (ml/kg/min)] was objectively measured using a treadmill test among 313 healthy men and women aged 40-44 years.<br /><em><strong>Results</strong></em>: Among men and women participating in both studies, the mean BMI was 27.1 kg/m2 for men and 25.1 kg/m2 for women. Mean arterial blood pressure (MAP) was 92.4 mm Hg for men and 86.0 mm Hg for women. The proportion defined as pre-hypertensive/hypertensive (systolic/diastolic blood pressure &gt; 120/80) were 33% and 56% for women and men, respectively. The proportion of low, medium and high CRF for both sexes combined differed significantly (p &lt; 0.0001) by BMI level (&lt; 25 or ≥ 25 kg/m2). Increased fitness tended to reduce blood pressure among overweight and obese men (p trend = 0.03), whereas increased fitness tended to reduce blood pressure among normal weighted women (p trend = 0.01).<br /><em><strong>Conclusion:</strong></em> Among healthy 40-44 year old men and women in this study, BMI was positively associated and CRF was negatively associated with blood pressure. Moreover, our results suggest that BMI may be a more important factor than CRF in predicting systolic blood pressure in both sexes. However, cardiorespiratory<br />fitness and weight control may both be important targets for prevention of hypertensio

Body fat, energy balance and estradiol levels: a study based on hormonal profiles from complete menstrual cycles

BACKGROUND: Female fecundity is regulated by nutritional status. Although widely cited, this hypothesis is not strongly supported by empirical data from non-obese, healthy women of reproductive age. METHODS: Healthy, reproductive aged women (n = 141) from Southern Poland collected daily morning saliva samples for one complete menstrual cycle. Levels of 17-b-estradiol were analyzed by radioimmunoassay. Anthropometric measurements, including body fat percentage, were taken randomly with respect to phase of the menstrual cycle. Energy balance was specified based on changes in body fat percentage from the beginning to the end of the observation period. RESULTS: Women with very low and high body fat had significantly lower levels of E2 compared with women with low and average body fat. In women of very low to average body fat, a 10% increase in body fat was associated with a 5 – 7 pmol/l increase in estradiol levels. The association between fat percentage and E2 was even stronger in women with positive energy balance, who also showed significant differences between body fat groups in estradiol profiles across whole the menstrual cycle. No such relationship was found in women with negative energy balance. CONCLUSIONS: In healthy women, we found a non-linear association between body fat and estradiol levels. Both very low and high body fat was associated with decreased estradiol levels. The relationship between estradiol and body fat was strongly influenced by women’s energy balance.AnthropologyHuman Evolutionary Biolog

Low estradiol levels in women of reproductive age having low sleep variation

Higher exposure to light at night per se and through decrease in sleep duration and night shift work may suppress serum melatonin levels, which in turn may increase the reproductive hormone levels. High levels of steroid hormones, especially estrogens, may be associated with an increase of the breast cancer risk. This study investigated whether variation in the sleep duration during one entire menstrual cycle corresponds to variation in estradiol levels in healthy, urban women of reproductive age. Ninthy five regularly menstruating women ages 24-36 collected daily saliva samples for one entire menstrual cycle and recorded the number of hours of sleep per night (sleep duration). Saliva samples were analyzed for concentration of 17-ß estradiol (E2). We documented, after adjustments for sleep duration, a positive relationship between the sleep variation (coefficient of variation in sleep duration - sleep CV) and estradiol levels in women of reproductive age. Mean levels of E2 differed significantly in women from the lowest sleep CV quartile in comparison to other quartiles (p<0.001). The low sleep variation group, that is the women who sleep regularly, had mean E2 levels 60% lower than other groups. These results suggest that sleep variation significantly correlates with E2 levels, while sleep duration does not show a statistically significant relationship. According to the breast cancer development hypothesis, increasing the lifetime exposure to endogenous estrogens could result in higher risk of breast cancer.AnthropologyHuman Evolutionary Biolog

Glutathione S-Transferase M1 Genetic Polymorphism Is Associated With Salivary 17-βestradiol Levels: A Study Based On Hormonal Profiles From Entire Menstrual Cycles

Introduction: Studies suggest that enzymes involved in the estrogen metabolic pathway are susceptibility factors for breast cancer; however, there is limited direct evidence in relation to estradiol levels. The glutathione-S-transferase M1 enzyme (GSTM1) enzyme is involved in estrogen peroxidation, and a shortage seems to enhance estrogen exposure. A homozygous deletion of the GSTM1 gene leads to total absence of enzyme activity, and studies indicate that an association with breast cancer risk may be modified by body mass. So far, parallel studies on intermediate biomarkers (i.e. estradiol) are largely missing. Thus, in the present study, we assessed the association between a GSTM1 genetic polymorphism (null/rs1065411) and daily salivary levels of 17-βestradiol throughout one entire menstrual cycle and evaluated modification of genotype effects according to metabolic profile in 190 premenopausal women aged 25-35 years. Methods: The women participated in the Energy Balance and Breast Cancer Aspects study (EBBA-I, 2000-2002) in Tromsø, North Norway (inclusion criteria: healthy, non-pregnant, non-lactating, no current use of exogenous hormones). Salivary levels of 17-βestradiol were assessed by radioimmunoassay (The Reproductive Ecology Laboratory, Harvard University). Height and weight were measured. Genomic DNA was extracted from EDTAwhole blood. GSTM1 genotyping was done on the ABI PRISM® 3100 Genetic Analyzer (Fred Hutchinson Cancer Research Center). The GSTM1 assay distinguishes between the GSTM1*Aallele (G nucleotide, Lys at aminoacid 173), the GSTM1*B allele (C nucleotide, Asn at aminoacid 173), and the homozygous gene deletion. Regression models were used to study the relation between genetic (null genotype versus all other alleles combined) and metabolic susceptibility factors, and levels of 17-βestradiol. Results: Mean body mass index (BMI) was 24.4 kg/m2. The homozygous gene deletion of GSTM1 had a prevalence of 52%, and the frequency of the null genotype was similar in heavy women (BMI ≥26.3 kg/m2, upper quartile) as compared to other women (p = .18). The null genotype was associated with lower levels of 17-βestradiol by cycle day compared to other alleles (p = .04). However, the association was confined to women that were normal weight to slightly overweight (p for interaction = .01). In women with BMI < 26.3 kg/m2, the null genotype was associated with significantly lower levels of 17-βestradiol by cycle day compared to other alleles (p = .02) and an 18% reduction in overall average level of 17-β estradiol throughout the cycle (p = .02), while in heavy women no association with estradiol levels was observed. Conclusion: In our study, GSTM1 genotype was a significant determinant of circulating estradiol levels in premenopausal women without marked adiposity. Thus, interestingly our results strongly support that the effect of body mass on estradiol levels and subsequent breast cancer development may be modified by GSTM1 genotype.AnthropologyHuman Evolutionary Biolog

The influence of metabolic factors and ethnicity on breast cancer risk, treatment and survival: The Oslo ethnic breast cancer study

Background - Breast cancer risk remains higher in high-income compared with low-income countries. However, it is unclear to what degree metabolic factors influence breast cancer development in women 30 years after immigration from low- to a high-incidence country. Methods - Using Cox regression models, we studied the association between pre-diagnostic metabolic factors and breast cancer development, and whether this association varied by ethnicity among 13,802 women participating in the population-based Oslo Ethnic Breast Cancer Study. Ethnic background was assessed and pre-diagnostic metabolic factors (body mass index, waist:hip ratio, serum lipids and blood pressure) were measured. A total of 557 women developed invasive breast cancer, and these women were followed for an additional 7.7 years. Results - Among women with an unfavorable metabolic profile, women from south Asia, compared with western European women, had a 2.3 times higher breast cancer risk (HR 2.30, 95% CI 1.18–4.49). Compared with the western European women, the ethnic minority women were more likely to present with triple-negative breast cancer (TNBC) (OR 2.11, 95% CI 0.97–4.61), and less likely to complete all courses of planned taxane treatment (OR 0.26, 95% CI 0.08–0.82). Among TNBC women, above-median triglycerides:HDL-cholesterol (>0.73) levels, compared with below-median triglycerides:HDL-cholesterol (≤0.73) levels, was associated with 2.9 times higher overall mortality (HR 2.88, 95% CI 1.02–8.11). Conclusions - Our results support the importance of metabolic factors when balancing breast cancer prevention and disease management among all women, and in particular among non-western women migrating from a breast cancer low-incidence to a high-incidence country

High tea consumption diminishes salivary 17beta-estradiol concetration in Polish women

Artykuł recenzowany / peer-reviewed articleWe hypothesized that among reproductive-age women consuming large quantities of tea, the production of estradiol would be suppressed. It has been shown that catechins and theaflavines, the major constituents of tea, inhibit aromatase, an enzyme which catalyses the conversion of androgens to estrogens. Our study included Polish women living in urban (N=61) and rural (N=48) areas. Women collected daily saliva samples for one complete menstrual cycle and filled out dietary questionnaires. Saliva samples were analyzed by radioimmunoassay for concentration of 17-β estradiol (E2). Women with high (above the median) average daily consumption of black tea had reduced levels of salivary E2, in comparison with women who drank less black tea (below median). This effect was observed within the whole study group, as well as separately within urban (p = 0.0006) and rural (p = 0.013) groups. High intake of the sum of subclasses of tea catechins and epigallocatechin gallate, assessed using the USDA database [http://www.nal.usda.gov], was also associated with lower concentrations of E2 within all women (p = 0.01 and p = 0.0001, respectively) and within the urban group (p = 0.0001 and p = 0.004, respectively). Similar relationships were observed between the sum of subclasses of theaflavines and thearubigines and E2 levels for the whole group (p = 0.002) and for urban women (p = 0.02). Women with high consumption of tea had lower levels of E2 concentration throughout the entire menstrual cycle. These results may have implications for reducing hormone-related cancer risk by a relatively easy dietary intervention.the State Committee for Scientific Research, Warsaw, Poland, project No. 3 P05E 016 25 and 6 P05D 112 20, the Radcliffe Institute of Advanced Study, Harvard University and the Norwegian Cancer Society

Adult Height, Insulin Levels and 17β-Estradiol in Young Women

Background: Adult height and insulin levels have independently been associated with breast cancer risk. However, little is known about whether these factors influence estradiol levels. Thus, we hypothesize that adult height in combination with insulin levels may influence premenopausal 17β-estradiol throughout the entire menstrual cycle of possible importance of breast cancer risk. Methods: Among 204 healthy women, aged 25-35 years who participated in the Norwegian EBBA I study, birth weight and age at menarche were assessed by questionnaire, personal health record and interview. 17β-estradiol concentrations were estimated by daily saliva samples throughout one entire menstrual cycle using radioimmunoassay (RIA). Measures of height (cm) were taken as well as waist circumference (cm), body mass index (BMI kg/m2) and total fat percentage (DEXA % fat). Fasting blood samples were drawn, and serum concentrations of insulin were determined. Results: The women reported a mean height of 166.5 cm, birth weight of 3389 g and age at menarche 13.1 years. Mean BMI was 24.4 kg/m2, mean waist circumference 79.5 cm and mean total fat percentage 34.1%. Women with an adult height of more than 170 cm and insulin levels higher than 90 pmol/L experienced on average an 37.2 % increase in 17β- estradiol during an entire menstrual cycle compared to those with the same height, and insulin levels below 90 pmol/L. Moreover, this was also observed throughout the entire menstrual cycle. Conclusion: Our findings support that premenopausal levels of 17β-estradiol vary in response to adult height and insulin levels, suggesting that women who become taller are put at risk for higher estradiol levels when their insulin levels rise of possible importance for breast cancer risk.Anthropolog

Normal and unusual days for dietary intake during the 12 months after a breast cancer diagnosis in women

Purpose There are several reasons to report days as being unusual with regard to dietary intake, including special occasions and celebrations. For breast cancer patients during the 12 month post-surgery period, unusual days may also include days that are afected by being a cancer patient. The aim of this study was to study dietary intake on “normal” and “unusual” days, and to study what is reported in “free text felds” of a food diary. Methods Women (n=456), mean age 55.5 years newly diagnosed with invasive breast cancer (stage I/II) were included in this clinical study. “Normal” and “unusual” days in general, over time and during the week and weekends were studied using repeated administration of a 7-day pre-coded food diary. Results The breast cancer patients reported 26% of all days as unusual. The intake of energy, most nutrients, especially alcohol and sugar, red and processed meat, and sweets, cakes, and snacks was 5–126% higher, whereas intake of fber, fruit and berries, vegetables, and dairy products was 7–17% lower on unusual than on normal days (P<0.001). The same pattern was seen for normal/unusual days during the weekdays, weekends and over time. Finally, 99% of the breast cancer patients used the free text felds to report additional intake with a mean energy of 1.1 MJ/day. Conclusion For breast cancer patients during the 12-month post-surgery period, unusual days are important drivers of total intake, especially for alcohol. The free text felds in the pre-coded food diary contributed substantially to the total intake

Exploring the effects of lifestyle on breast cancer risk, age at diagnosis, and survival: the EBBA-Life study

Purpose - Whether an unfavorable lifestyle not only affects breast cancer risk, but also influences age at onset of breast cancer and survival, is under debate. Methods - In a population-based cohort, the Energy Balance and Breast Cancer Aspects throughout life (EBBA-Life) study, a total of 17,145 women were included. During follow-up, 574 women developed invasive breast cancer. Breast cancer cases were followed for an additional 9.1 years. Detailed medical records were obtained. Cox’s proportional hazard regression models were used to study the association between pre-diagnostic lifestyle factors (weight, physical activity, alcohol use, smoking, and hypertension), breast cancer risk, age at diagnosis, and survival. Results - At study entry, 34.3% of the participating women were overweight and 30.7% were physically inactive. Mean age at breast cancer diagnosis was 58.0 years, and 78.9% of the tumors were estrogen receptor positive. Among menopausal women who did not use hormone therapy and had an unfavorable lifestyle (3–5 unfavorable factors), compared with women who had a favorable lifestyle, we observed a twofold higher risk for postmenopausal breast cancer (hazard ratio [HR] 2.13, 95% confidence interval [CI] 1.23–3.69), and they were 3.4 years younger at diagnosis (64.8 versus 68.2 years, P = 0.032). Breast cancer patients with an unfavorable lifestyle, compared with patients with a favorable lifestyle, had almost a two times higher overall mortality risk (HR 1.96, 95% CI 1.01–3.80). Conclusions - Our study supports a healthy lifestyle improving breast cancer prevention, postponing onset of disease, and extending life expectancy among breast cancer patients