Anne-Sofie Furberg

Physical activity and cancer risk: dose-response and cancer, all sites and site-specific.

PURPOSE The association between physical activity and overall and site-specific cancer risk is elaborated in relation to whether any observed dose-response association between physical activity and cancer can be interpreted in terms of how much physical activity (type, intensity, duration, frequency) is needed to influence site- and gender-specific cancer risk. METHODS Observational studies were reviewed that have examined the independent effect of the volume of occupational physical activity (OPA) and/or leisure time physical activity (LPA) on overall and site-specific cancer risk. RESULTS The evidence of cohort and case-control studies suggests that both leisure time and occupational physical activity protect against overall cancer risk, with a graded dose-response association suggested in both sexes. Confounding effects such as diet, body weight, and parity are often included as a covariate in the analyses, with little influence on the observed associations. A crude graded inverse dose-response association was observed between physical activity and colon cancer in 48 studies including 40,674 colon/colorectal cancer cases for both sexes. A dose-response effect of physical activity on colon cancer risk was especially observed, when participation in activities of at least moderate activity (>4.5 MET) and demonstrated by activities expressed as MET-hours per week. An observed inverse association with a dose-response relationship between physical activity and breast cancer was also identified in the majority of the 41 studies including 108,031 breast cancer cases. The dose-response relationship was in particular observed in case-control studies and supported by observations in cohort studies when participation in activities of at least moderate activity (>4.5 MET) and demonstrated by activities expressed by MET-hours per week. This association between physical activity and breast cancer risk is possibly dependent on age at exposure, age at diagnosis, menopausal status and other effect modifiers, e.g., body mass index. Furthermore, data concerning carcinoma of other cancers (prostate, lung, endometrium, ovary, and testicular cancers) are required. CONCLUSION A protective effect of physical activity on site-specific cancer risk with a dose-response association between physical activity and colon and pre- and postmenopausal breast cancer supported by identified biological mechanisms has been observed. The optimal permutation of type, intensity, duration, and frequency of physical activity across the lifespan is unclear, but it is gender, age, and site specific and supports moderate activity (>4.5 MET) more than light activities (<4.5 MET). The complicated nature of the physical activity variable, combined with lack of knowledge regarding possible biological mechanisms operating between physical activity and cancer, warrants further studies including controlled clinical randomized trials.

Metabolic abnormalities (hypertension, hyperglycemia and overweight), lifestyle (high energy intake and physical inactivity) and endometrial cancer risk in a Norwegian cohort.

Since high energy intake, inactivity, hypertension and diabetes are linked to obesity and an unfavorable hormonal profile, we wanted to test whether energy intake, physical activity, blood pressure and serum glucose are related to the risk of endometrial cancer independent of the body mass index (BMI). A cohort of 24,460 women, aged 20–49 years, attended a Norwegian health screening twice during 1974–1981; they answered questions about diet, physical activity and chronic diseases, and their height, weight, blood pressure and non‐fasting serum glucose were measured. By the end of 1996, during 15.7 years of follow‐up, 130 cases of endometrial carcinomas were identified. The relative risks (RRs) for endometrial cancer were estimated in proportional hazards models including potentially confounding factors. Obese women (BMI ≥ 30 kg/m2) were at 2.6 times increased risk of endometrial cancer compared to normal weight women (BMI < 25 kg/m2) (RR = 2.57, 95%CI = 1.61–4.10). Among overweight women (BMI ≥ 25 kg/m2), non‐fasting serum glucose in the upper quartile vs. in the lower quartile was associated with a 2.4 times increase in risk (RR = 2.41, 95%CI = 1.08–5.37), whereas among obese women, blood pressure above 140/90 mmHg vs. below 140/90 mmHg in both surveys was associated with a 3.5 times increase in risk (RR = 3.47, 95%CI = 1.24–9.70). Especially in women younger than 50 years, high energy intake (5,044–6,401 kJ/day) conferred higher risk compared to low energy intake (< 4266 kJ/day) (RR = 3.40, 95%CI = 1.52–7.60). Increasing recreational activity tended to be protective. Among obese women with non‐sedentary jobs at both screenings, RR declined to 0.18 (95%CI = 0.05–0.62) as the level of sustained occupational activity increased (ptrend = 0.03). Our results suggest that inactivity and high energy intake are major risk factors for endometrial cancer independent of BMI, and that hypertension and relative hyperglycemia are significant markers of risk, especially among the heaviest women.

Staphylococcus aureus: Determinants of human carriage

Staphylococcus aureus is a common human commensal but carriage varies between e.g. geographic location, age, gender, ethnicity and body niche. The nares, throat and perineum are the most prevalent sites for carriage in the general adult population. Other sites of the skin and the intestine are also frequently colonised. Thus, a successful establishment is dependent on multiple factors. This review describes results from observational studies of S. aureus carriage and the influence bacterial, host and environmental/modifiable factors might have on the relationship.

17-beta-Estradiol in relation to age at menarche and adult obesity in premenopausal women

BACKGROUND We hypothesize that premenopausal endogenous estradiol may be associated with age at menarche and adult overweight and obesity, potentially contributing to breast cancer risk. METHODS We assessed age at menarche by questionnaire among 204 healthy Norwegian women, aged 25-35 years. Measures of body composition included body mass index (BMI, kg/m(2)), waist circumference (WC, cm), waist-to-hip ratio (WHR) and fat percentage dual energy X-ray absorptiometry, (DEXA). Daily salivary 17-beta-estradiol (E(2)) concentrations were collected throughout one entire menstrual cycle and assessed by radioimmunoassay (RIA). Linear regression analyses and linear mixed models for repeated measures were used and potential confounding factors and effect modifiers were tested. RESULTS Among women with an early age at menarche (< or =12 years), the overall mean salivary E(2) concentration increased by 3.7 pmol/l (95% confidence interval, 1.8-5.7 pmol/l) with each 9.8 cm (1 SD) increase in WC, which represents a 20.7% change in the mean for the total group. Among the same early maturers, a 1 SD (0.06) change in WHR was directly associated with a 24.0% change in mean E(2) concentration for the total group. CONCLUSIONS Our findings support the hypothesis that early age at menarche, together with adult overweight and obesity, result in high levels of 17-beta-estradiol throughout the menstrual cycle.

Does a variation in self-reported physical activity reflect variation in objectively measured physical activity, resting heart rate, and physical fitness? Results from the Tromsø study

Aims: To study the association between self-reported physical activity (PA) and objectively measured PA, resting heart rate, and physical fitness. Methods: During 2007—08, 5017 men and 5607 women aged 30—69 years attended the sixth survey of the Tromsø study. Self-reported PA during leisure-time and work were assessed and resting heart rate was measured. In a sub-study, the activity study, PA (Actigraph LLC) and physical fitness (VO2max) were objectively measured among 313 healthy men and women aged 40—44 years. Results: Self-reported leisure PA was significantly correlated with VO2max (ml/kg/min) (women 0.40, p < 0.001, men 0.44 p < 0.001) and moderate-to-vigorous PA (>2000 counts/min) (women 0.28, p < 0.01, men 0.25, p < 0.01). The intra-class correlation coefficient between self-reported leisure PA and overall PA (counts/min) measured by accelerometer was 0.62 (95% CI 0.51, 0.71) for women and 0.59 (95% CI 0.47, 0.69) for men, and for VO2max the intra-class correlation coefficient was 0.86 (95% CI 0.81, 0.90) for both sexes. Among all participants, an inverse dose—response relationship was observed between self-reported leisure PA and resting heart rate for both men and women (p < 0.0001). More women than men met the international recommendations of 10,000 step counts/day (27% vs. 22%) and the recommendation of at least 30 minutes/day of moderate-to-vigorous intensities (30% vs. 22 %). Conclusions: The Tromsø physical activity questionnaire has acceptable validity and provides valid estimates of high-intensity leisure activity. However, these results underscore the need for collecting objectively PA measurements in large epidemiological studies.

Age- and Gender-Associated Staphylococcus aureus spa Types Found among Nasal Carriers in a General Population: the Tromsø Staph and Skin Study

ABSTRACT Staphylococcus aureus nasal carriers risk autoinfection; however, knowledge about the factors that make specific strains successful colonizers is limited. This study was undertaken to identify the most successful S. aureus clones in nasal carriers and compare their distribution among host groups. The population structure of S. aureus isolates from healthy adults was investigated by spa typing 1,981 isolates from persistent and intermittent nasal carriers participating in a health survey. In the baseline screening (1,113 isolates), the most common spa types were t012 (8.4%), t084 (7.6%), and t065 (4.9%). Three large spa clonal complexes (spa CC012, spa CC065, and spa CC084) comprised 62.4% of the isolates. In multivariate models adjusted for age and smoking status, male sex was associated with higher risk for spa type t084 (odds ratio [OR], 1.72; 95% confidence interval [CI], 1.06 to 2.77), and lower risk of spa type t012 (OR, 0.60; 95% CI, 0.39 to 0.92) colonization. The prevalence of spa type t012 decreased significantly with increasing age (P = 0.03), with a prevalence almost twice as high in the youngest group (age 30 to 44 years, prevalence = 11.1%) as in the oldest group (age, 60 to 87 years; prevalence = 5.6%). Among baseline isolates, spa type t084 had a twofold-higher prevalence among intermittent carriers than among persistent carriers (10.6% versus 5.5%; P = 0.04). In summary, the two most prevalent spa types found in this study were significantly associated with age and/or gender. This may provide valuable clues to the multifactorial mechanisms, among them bacterial factors, involved in nasal colonization with S. aureus.

Prevalence and population structure of Staphylococcus aureus nasal carriage in healthcare workers in a general population. The Tromso Staph and Skin Study.

SUMMARY Healthcare workers (HCWs) may be a reservoir for Staphylococcus aureus transmission to patients. We examined whether HCW status is associated with S. aureus nasal carriage and population structure (spa types) in 1302 women (334 HCWs) and 977 men (71 HCWs) aged 30–69 years participating in the population-based Tromsø Study in 2007–2008. Multivariable logistic regression models were used. While no methicillin-resistant S. aureus (MRSA) was isolated, overall, 26·2% of HCWs and 26·0% of non-HCWs were S. aureus nasal carriers. For women overall and women residing with children, the odds ratios for nasal carriage were 1·54 [95% confidence interval (CI) 1·09–2·19] and 1·86 (95% CI 1·14–3·04), respectively, in HCWs compared to non-HCWs. Moreover, HCWs vs. non-HCWs had a 2·17 and 3·16 times higher risk of spa types t012 and t015, respectively. This supports the view that HCWs have an increased risk of S. aureus nasal carriage depending on gender, family status and spa type.

Obesity and Staphylococcus aureus Nasal Colonization among Women and Men in a General Population

Background Obesity and diabetes mellitus (DM) have been linked to increased risk of infections, and Staphylococcus aureus nasal colonization is a major risk factor for developing infections with the microbe. We therefore sought to find whether body mass index (BMI) and waist circumference (WC) could be associated with S. aureus colonization independent of DM. Methodology S. aureus colonization was assessed by nasal swab cultures among 2,169 women and 1,709 men, aged 30–87 years, in the population-based Tromsø Staph and Skin Study in 2007–08. Height (cm), weight (kg), WC (cm), and glycated haemoglobin (HbA1c,%) were measured. Multivariable logistic regression analyses including information on DM, HbA1c, hormonal contraceptive use and other potential confounders were used. Results In the female population, each 2.5 kg/m2 increase in BMI was associated with a 7% higher odds of S. aureus nasal colonization (P = 0.01). When comparing obese and lean women aged 30–43 years, we observed that BMI ≥32.5 versus <22.5 kg/m2 and WC ≥101 versus <80 cm was associated with a 2.60 and 2.12 times higher odds of S. aureus colonization, respectively (95% confidence intervals 1.35–4.98 and 1.17–3.85). Among men, high WC was also associated with S. aureus nasal colonization. The associations did not change significantly when the analysis was restricted to participants without signs of pre-diabetes (HbA1c <6.0%) among women and men, and to non-users of hormonal contraceptives among women. Conclusion Our results support that obesity is a possible determinant for S. aureus nasal colonization independent of DM, in particular for premenopausal women. The role of obesity at different ages and by sex should be addressed in future prospective studies of S. aureus colonization.

Marriage and motherhood are associated with lower testosterone concentrations in women

Testosterone has been hypothesized to modulate the trade-off between mating and parenting effort in males. Indeed, evidence from humans and other pair-bonded species suggests that fathers and men in committed relationships have lower testosterone levels than single men and men with no children. To date, only one published study has examined testosterone in relation to motherhood, finding that mothers of young children have lower testosterone than non-mothers. Here, we examine this question in 195 reproductive-age Norwegian women. Testosterone was measured in morning serum samples taken during the early follicular phase of the menstrual cycle, and marital and maternal status were assessed by questionnaire. Mothers of young children (age ≤3) had 14% lower testosterone than childless women and 19% lower testosterone than women who only had children over age 3. Among mothers, age of the youngest child strongly predicted testosterone levels. There was a trend towards lower testosterone among married women compared to unmarried women. All analyses controlled for body mass index (BMI), age, type of testosterone assay, and time of serum sample collection. This is the first study to look at testosterone concentrations in relation to marriage and motherhood in Western women, and it suggests that testosterone may differ with marital and maternal status in women, providing further corroboration of previous findings in both sexes.

Physical Activity, Heart Rate, Metabolic Profile, and Estradiol in Premenopausal Women

PURPOSE To study whether physical inactive women with a tendency to develop metabolic syndrome have high levels of 17beta-estradiol (E2) of importance for breast cancer risk. METHODS Two hundred and four healthy women of reproductive age were assessed for self-reported leisure-time physical activity (LPA), resting heart rate (HR), blood pressure (BP), anthropometry, and serum glucose, lipids, and insulin [Norwegian Energy Balance and Breast Cancer Aspect (EBBA) study]. E2 was measured in daily saliva samples throughout an entire menstrual cycle. A clustered metabolic risk score [z metabolic syndrome (zMS); total cholesterol-high-density lipoprotein-cholesterol (HDL-C) ratio, insulin resistance, total fat tissue, BP, and triglycerides] was defined. Linear regression and linear mixed models were used, and confounding factors were tested. RESULTS Physically active women had lower fat percentage (Ptrend = 0.003) and HRs (Ptrend = 0.003) than sedentary women. We estimated an increase in E2 of 1.27 pmol.L [95% confidence interval (CI), 0.06-2.47] for each 11.7 beats.min (1 SD) increase in HR, and this corresponds to the 7% change in mean concentration of E2 for the total group. Associations with E2 were also found for fat tissue, total cholesterol-HDL-C ratio, insulin resistance, and triglycerides. A dose-response relationship was observed among the three levels of LPA and HR and zMS (Ptrend = 0.03 for LPA; Ptrend = 0.004 for HR). Women in the highest tertile of the clustered metabolic risk score had average salivary E2profiles that were markedly higher, throughout the cycle, than those of the other groups, with a cycle peak-day difference in E2 of 22-28%. CONCLUSION LPA and HR were associated with metabolic risk score, and this score was associated with daily level of E2, pointing to important biologic mechanisms operating between a sedentary lifestyle and an increased breast cancer risk.