Inger Thune

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.

Body mass index and survival in women with breast cancer—systematic literature review and meta-analysis of 82 follow-up studies

The current systematic literature review and meta-analysis extends and confirms the associations of obesity with an unfavourable overall and breast cancer survival in pre and postmenopausal breast cancer, regardless of when BMI is ascertained. Increased risks of mortality in underweight and overweight women and J-shape associations with total mortality were also observed. The recommendation of maintaining a healthy body weight throughout life is important as obesity is a pandemic health concern.

Large breasts and narrow waists indicate high reproductive potential in women

Physical characteristics, such as breast size and waist–to–hip ratio (WHR), function as important features used by human males to assess female attractiveness. Males supposedly pay attention to these features because they serve as cues to fecundity and health. Here, we document that women with higher breast–to–underbreast ratio (large breasts) and women with relatively low WHR (narrow waists) have higher fecundity as assessed by precise measurements of daily levels of 17–β–oestradiol (E2) and progesterone. Furthermore, women who are characterized by both narrow waists and large breasts have 26% higher mean E2 and 37% higher mean mid–cycle E2 levels than women from three groups with other combinations of body–shape variables, i.e. low WHR with small breasts and high WHR with either large or small breasts. Such gains in hormone levels among the preferred mates may lead to a substantial rise in the probability of conception, thus providing a significant fitness benefit.

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.

Physical activity and risk of colorectal cancer in men and women

We examined the association between self-reported occupational and recreational physical activity and the subsequent risk of colorectal cancer in a population-based cohort in Norway. During a mean follow-up time of 16.3 years for males and 15.5 years for females, 236 and 99 colon cancers and 170 and 58 rectal cancers were observed in males and females, respectively, among 53,242 males and 28,274 females who attended the screening between 1972 and 1978. Physical activity at a level equivalent to walking or bicycling for at least four hours a week during leisure-time was associated with decreased risk of colon cancer among females when compared with the sedentary group (RR = 0.62, 95% CI 0.40-0.97). Reduced risk of colon cancer was particularly marked in the proximal colon (RR = 0.51, 95% CI 0.28-0.93). This effect was not observed for occupational physical activity alone, probably due to a narrow range of self-reported physical activity at work among females. However, by combining occupational and recreational physical activity we observed an inverse dose-response effect as increasing total activity significantly reduced colon cancer risk (P for trend = 0.04). Among males 45 years or older at entry to the study, an inverse dose-response effect was observed between total physical activity and colon cancer risk (P for trend = 0.04). We also found in males a stronger preventive effect for physical activity in the proximal as compared to distal colon. In addition, we found a borderline significant decrease in colon cancer risk for occupational physical activity in males 45 years or older when compared to the sedentary group (RR = 0.74, 95% CI 0.53-1.04). All results were adjusted for age, body mass index, serum cholesterol and geographic region. No association between physical activity and rectal cancer was observed in males or females. The protective effect of physical activity on colon cancer risk is discussed in regard to energy balance, dietary factors, age, social class, body mass index and gastrointestinal transit time.

Physical activity and the risk of prostate and testicular cancer: a cohort study of 53,000 Norwegian men.

The associations between recreational and occupational physical activity and the subsequent risk of prostate and testicular cancer were examined in a population-based cohort study of 53,242 men in Norway. Age at study entry was 19 to 50 years. Information on physical activity was based on questionnaire responses and a brief clinical examination. A total of 220 prostate and 47 testicular cancer cases were recorded in the Cancer Registry of Norway during a mean follow-up time of 16.3 years. We found a nonsignificant, reduced, adjusted relative risk (RR) of prostate cancer with increased level of physical activity at work and among those men with the greatest recreational physical activity. When occupational and recreational physical activity were combined, a reduced adjusted risk of prostate cancer was observed among men who walked during occupational hours and performed either moderate recreational activity (RR-0.61, 95 percent confidence interval [CI]=0.36 to 1.01) or regular recreational training (RR=0.45, CI=0.20 to 1.01) relative to sedentary men (test for trend,P=0.03). Physically active men who were older than 60 years of age at diagnosis showed a reduced adjusted RR of borderline significance, while no association was observed for younger men. No evidence was found for any association between physical activity and testicular cancer regardless of physical activity at work and recreation.

The influence of physical activity on lung-cancer risk: A prospective study of 81,516 men and women

Physical activity is inversely related to mortality from respiratory diseases including lung cancer. Physical activity improves pulmonary function but its impact on lung‐cancer risk has not been studied much. During 1972–1978, 53,242 men and 28,274 women, aged 20 to 49 years, participated in a population‐based health survey and were followed until 31 December 1991. We observed a total of 413 men and 51 women with lung cancer. Leisure activity and work activity were assessed using a questionnaire in 4 categories. In a sub‐cohort, physical activity was assessed twice at an interval of 3 to 5 years. Leisure but not work activity was inversely related to lung‐cancer risk in men after adjustment for age, smoking habits, body‐mass index and geographical residence (p for trend = 0.01). Men who exercised at least 4 hours a week had a lower risk than men who did not exercise [relative risk (RR) = 0.71; 95% confidence interval (CI) = 0.52–0.97]. Reduced risk of lung cancer was particularly marked for small‐cell carcinoma (RR = 0.59; 95% CI = 0.38–0.94) and for adenocarcinoma RR = 0.65; 95% CI = 0.41–1.05), with no association seen for squamous‐cell carcinoma. In the sub‐cohort in which physical activity was assessed twice, the risk of lung cancer was particularly reduced among men who were most active at both assessments (RR = 0.39; 95% CI = 0.18–0.85). No consistent association between physical activity and lung‐cancer risk was observed among women. Our results suggest that leisure physical activity has a protective effect on lung‐cancer risk in men. The small number of incident cases, combined with the narrow range of physical activity reported, may have limited our ability to detect an association between physical activity and lung cancer in women.

Fatness at birth predicts adult susceptibility to ovarian suppression: An empirical test of the Predictive Adaptive Response hypothesis

Poor fetal environments are thought to produce adaptive changes in human developmental trajectories according to the Predictive Adaptive Response hypothesis. Although many studies have demonstrated correlations between indicators of fetal environment and negative adult health outcomes, the adaptive significance of these outcomes is unclear. Our study explicitly tests the adaptive nature of fetal programming in humans. We show that differences in nutritional status at birth are associated with adaptive differences in the sensitivity of adult ovarian function to energetic stress. Women who were born as relatively fat babies do not exhibit ovarian suppression in response to moderate levels of physical activity at adulthood, in contrast to women who were born as skinnier babies. The levels of estradiol in women born in the highest tertile of ponderal index (an indicator of neonatal nutritional status) were 37% and 46% higher, respectively, than levels of estradiol in women born in the low and middle ponderal index tertiles. These findings suggest that fetal programming of reproductive function results in developmentally plastic, but essentially adaptive, shifts in set points of ovarian response to energetic stress, such that women who were gestated under conditions of energetic constraint show greater sensitivity to energetic stress in adulthood. Our results have practical implications in terms of behavioral strategies for reducing the risk of breast cancer. We suggest that the amount of activity necessary to reduce levels of estrogen, which may in turn reduce cancer risk, can depend on a womans nutritional status at birth.

Psychosocial interventions as part of breast cancer rehabilitation programs? Results from a systematic review

Objective: This systematic review aimed to determine the effectiveness of psychoeducation, cognitive behavioural therapy (CBT) and social support interventions used in the rehabilitation of breast cancer (BC) patients.

A review of physical activity and prostate cancer risk

AbstractObjectives: The purpose was to review the etiologic role and the possible biologic mechanisms for physical activity in the primary prevention of prostate cancer and to identify future research priorities. Methods: We conducted literature searches and systematically reviewed all the epidemiologic studies of physical activity and prostate cancer and the literature on the underlying biologic mechanisms. Results: Among 24 previously conducted studies, 14 studies suggested an inverse association of physical activity on prostate cancer; however, no overall association was found in six studies and an increased risk of prostate cancer was observed amongst the most physically active men in four other studies. The methodologic limitations in these studies include variations in detection of latent disease and possible outcome misclassification, crude assessments of physical activity, inadequate control for confounding, and incomplete examination of effect modification. Conclusions: Physical activity may have an inverse association with prostate cancer risk; however, the epidemiologic evidence is currently inconsistent and the magnitude of the risk reduction observed is small. These inconsistent results could be attributable, in part, to methodologic limitations of previous studies. Hence, further investigation of the etiologic role of physical activity is needed before more definitive conclusions can be made. Specifically, research studies should be designed to measure all types and parameters of physical activity throughout lifetimes. Furthermore, a better understanding of the biologic mechanisms and etiologically relevant time periods in prostate carcinogenesis when physical activity may be operative is needed, so that these studies can be properly designed.