Mammographic density and its interaction with other breast cancer risk factors in an Asian population.

BACKGROUND: Joint effects of mammographic density and other risk factors on breast cancer risk remain unclear. METHODS: From The Singapore Breast Screening Project, we selected 491 cases and 982 controls. Mammographic density was measured quantitatively. Data analysis was by conditional logistic regression. RESULTS: Density was a significant risk factor, adjusting for other factors. Density of 76-100% had an odds ratio of 5.54 (95% CI 2.38-12.90) compared with 0-10%. Density had significant interactions with body mass index and oral contraceptive use (P=0.02). CONCLUSIONS: Percent density increases breast cancer risk in addition to effects of other risk factors, and modifies the effects of BMI and OCs.

Effect of population screening for type 2 diabetes on mortality: long-term follow-up of the Ely cohort.

AIMS/HYPOTHESIS: The aim of this study was to assess the impact of invitation to screening for type 2 diabetes and related cardiovascular risk factors on population mortality. METHODS: This was a parallel-group population-based cohort study including all men and women aged 40-65 years, free of known diabetes, registered with a single practice in Ely, UK (n = 4,936). In 1990-1992, approximately one-third (n = 1,705) were randomly selected to receive an invitation to screening for diabetes (with an OGTT) and related cardiovascular risk factors. In the remaining two-thirds of the population, 1,705 individuals were randomly selected for invitation to screening in 2000-2003 and 1,526 were not invited at any point during the follow-up period. All individuals were flagged for mortality until January 2008. RESULTS: There were 345 deaths between 1990 and 1999 (median 10 years follow-up). Compared with those not invited, individuals who were invited to the 1990-1992 screening round had a non-significant 21% lower all-cause mortality (HR 0.79 [95% CI 0.63-1.00], p = 0.05) after adjustment for age, sex and deprivation. There were 291 deaths between 2000 and 2008 (median 8 years follow-up), with no significant difference in mortality between invited and non-invited participants in 2000-2003. Compared with the non-invited group, participants who attended for screening at any time point had a significantly lower mortality and those who did not attend had a significantly higher mortality. CONCLUSIONS/INTERPRETATION: Invitation to screening was associated with a non-significant reduction in mortality in the Ely cohort between 1990 and 1999, but this was not replicated in the period 2000-2008. This study contributes to the evidence concerning the potential benefits of population screening for diabetes and related cardiovascular risk factors.

Effects of physical activity on evolution of proximal femur structure in a younger elderly population.

INTRODUCTION: For a fixed weight, a wider bone of standardised length is stiffer. But moving the cortices away from the centre of mass risks creating structural (elastic) instability, and hip fractures have been postulated to occur as a consequence of buckling of the thinned supero-lateral femoral neck cortex during a fall. We hypothesised that stereotyped physical activity (e.g., walking) may help conserve bending resistance (section modulus, Z) through redistribution of bone tissue, but it might be at the expense of supero-lateral cortical stability. METHODS: Hip structural analysis (HSA) software applied to DXA scans was used to derive measurements of section modulus and distances of a cross-section's centre of mass from the supero-lateral cortical margin (lateral distance, in cm). DXA scans were obtained on 1361 men and women in the EPIC-Norfolk population-based prospective cohort study. Up to 4 repeat DXA scans were done in 8 years of follow-up. Weight, height and activities of daily living were assessed on each occasion. A detailed physical activity and lifestyle questionnaire was administered at baseline. The lateral distance was measured on three narrow cross-sections with good precision: narrow neck (NN, coefficient of variation 2.6%), intertrochanter (IT) and shaft (S). A linear mixed model was used to assess associations with predictors. RESULTS: Ageing was associated with medial shifting of the centre of mass, so that lateral distance increased. Both greater weight and height were associated with greater lateral distance (P<0.0001). Among physical activity-related variables, walking/cycling for >1 h/day (P=0.025), weekly time spent on moderate impact activity (P=0.003), forced expiratory volume in 1 s (NN and IT, P<0.026) and lifetime physical activity (IT, P<0.0001) were associated with higher lateral distance. However, after adjusting for these variables, activities of daily living scores (NN, P<0.0001) and weekly time spent on low impact hip flexing activities were associated with shorter lateral distance (P=0.001). Greater baseline lateral distance was significantly associated with increased risk of subsequent hip fracture (n=26) in females (P<0.05, all regions) independently of age, height and bone mineral content. CONCLUSION: The age-related shift medially of the centre of mass of the femoral neck and trochanter may have adverse effects on fracture resistance in the event of a fall, so compromising the beneficial effects of walking on fitness, strength and risk of falling. The role of more diverse physical activity patterns in old age that impose loading on the supero-lateral cortex of the femur, involving for example hip flexion and stretching, needs investigation for their ability to correct this medial shifting of the centre of mass.

The UK case-control study of cerebral oedema complicating diabetic ketoacidosis in children.

AIMS/HYPOTHESIS: Cerebral oedema complicating diabetic ketoacidosis (DKA) remains the major cause of morbidity and mortality in children with type 1 diabetes, but its aetiology remains unknown. Our objective was to determine the impact of baseline biochemical factors and of treatment-related variables on risk of the development of cerebral oedema in children with DKA. MATERIALS AND METHODS: This was a national UK case-control study. Through the British Paediatric Surveillance Unit we identified 43 cases of cerebral oedema. Through a parallel reporting system, we also identified 2,940 episodes of DKA and selected 169 control subjects on the basis of comparable age, sex, numbers of new or known cases of diabetes and date of admission. Baseline biochemical data and treatment-related variables were extracted from the clinical notes of cases and control subjects. RESULTS: Allowing for differences in age, sex and new or known diabetes, cases were more acidotic at diagnosis of DKA (odds ratio [OR] for events in the least acidotic compared with the most acidotic tertile=0.02 [95% CI: 0.002-0.15], p<0.001). In addition, cases had higher potassium and urea levels at baseline. Calculated osmolality and baseline glucose were not significantly different. After allowing for severity of acidosis, insulin administration in the first hour (OR 12.7 [1.41-114.5], p=0.02) and volume of fluid administered over the first 4 h (OR 6.55 [1.38-30.97], p=0.01) were associated with risk. Low baseline plasma sodium and an elevated p(a)CO(2) also contributed to risk in the final regression model. Bicarbonate administration was not associated with increased risk of an event when corrected for acidosis. CONCLUSIONS/INTERPRETATION: In this case-control study of DKA, baseline acidosis and abnormalities of sodium, potassium and urea concentrations were important predictors of risk of cerebral oedema. Additional risk factors identified were early administration of insulin and high volumes of fluid. These observations should be taken into account when designing treatment protocols.

How much might achievement of diabetes prevention behaviour goals reduce the incidence of diabetes if implemented at the population level?

AIMS/HYPOTHESIS: Randomised trials targeting high-risk people with impaired glucose tolerance have halved progression to diabetes using behavioural interventions aimed at achieving five goals related to weight, diet and physical activity. The number of people currently meeting these goals in the general population is unknown. The potential impact on the incidence of diabetes of increasing the proportion of people who meet these goals is also unclear. We quantified the association between the achievement of behavioural goals for the prevention of diabetes and the incidence of diabetes in a population-based cohort study. SUBJECTS AND METHODS: European Prospective Investigation into Cancer (EPIC)-Norfolk is a prospective cohort of 24,155 participants aged 40-79 years who attended a baseline health check and completed validated diet and activity questionnaires. We assessed the association between achievement of five diabetes healthy behaviour prevention goals (BMI <25 kg/m(2), fat intake <30% of energy intake, saturated fat intake <10% of energy intake, fibre intake > or =15 g/4,184 kJ, physical activity >4 h/week) and risk of developing diabetes at follow-up (mean 4.6 years). RESULTS: Only 20% of EPIC participants met three or more diabetes prevention goals. Diabetes incidence was inversely related to the number of goals achieved (p<0.001). None of the participants who met all five goals developed diabetes, whereas diabetes incidence was highest in those who did not meet any goals. If the entire population were able to meet one more goal, the total incidence of diabetes would be predicted to fall by 20%. CONCLUSIONS/INTERPRETATION: In this population-based study, the risk of diabetes was inversely associated with the number of behaviour goals for diabetes prevention that were met. Interventions that promote achievement of these goals in the general population could significantly reduce the growing burden of diabetes-related morbidity and mortality.

Interaction of dense breast patterns with other breast cancer risk factors in a case-control study.

The question of interactions between breast density and other breast cancer risk factors is of interest, since it bears upon the use of density as a marker for changes in breast cancer risk. We studied breast parenchymal patterns and 13 other potential risk factors for breast cancer in 172 breast cancer cases and 338 age-matched controls in Singapore. Dense breast patterns were defined as having Tabar parenchymal pattern IV or V. We found significant interactions between dense patterns and ethnic group (P=0.046), and between dense patterns and number of deliveries (P=0.04). Among women with nondense breast patterns, the non-Chinese had lower risk than the Chinese with an odds ratio (OR) of 0.47 (95% CI 0.24, 0.88), whereas in those with dense patterns, the non-Chinese had considerably higher risks (OR=5.34, 95% CI 0.54, 52.51). Alternatively expressed, the increased risk with dense patterns was only observed in the non-Chinese (OR=13.99, 95% CI 1.33, 146.99). Among parous women, the protective effect of three or more deliveries was only observed in those with dense breast patterns (OR=0.21, 95% CI 0.06, 0.70). Suggestive but nonsignificant interactions with dense patterns were observed for ever having delivered, age at first delivery, breast feeding and body mass index. The results are consistent with dense breast patterns as a marker for hormonal modification of breast cancer risk.

Hip section modulus, a measure of bending resistance, is more strongly related to reported physical activity than BMD.

We hypothesized that measures of physical activity would have a closer relationship with section modulus (SM), an indicator of bending resistance, than with bone mineral density (BMD) because physical activity might expand the bony envelope, which tends to reduce BMD for a constant bone mineral content. Four hundred twenty-three men and 436 women (mean age 72 years, SD =3) were recruited from a prospective population-based cohort study to a study of hip bone loss. Hip BMD was measured on two occasions 2-5 years apart (mean 2.7, DXA-Hologic 1,000 W). Hip structural analysis (HSA) software was used to calculate SM and BMD from the DXA scans on three narrow regions: the narrow neck (NN), intertrochanter (IT) and shaft (S). A physical activity and lifestyle questionnaire was administered at baseline. Multivariate repeated measures analysis of variance was used to model the associations between personal attributes (weight, height, age), physical activity and lifestyle variables with SM, cross-sectional area (CSA), sub-periosteal diameter (PD) and BMD. Men and women were analysed together after tests for interactions with gender, which were found not to be significant. In all regions female gender was associated with having lower values of all outcomes, and body weight was positively associated with all outcomes, i.e., SM, CSA, PD and BMD ( P<0.0001). Sub-periosteal diameter was positively associated with reported lifetime physical activity (IT and S, P<0.0001). There was a significant decline of BMD with age at the NN and S regions ( P<0.026), and the PD increased with age (NN and S, P<0.019). Previous fracture history was associated with having lower values of BMD, SM and CSA (except for S; P<0.022). Both section modulus and CSA were positively associated with heavy physical activity after age 50 years in all regions ( P<0.019), whereas NN BMD was the only BMD associate of heavy physical activity after 50 ( P=0.036). Time spent per week on recreational activities classified as no impact activity was positively associated with BMD, CSA and SM (multivariate P<0.016). In conclusion, proximal femur diameter is associated positively with reported life-long physical activity. If this is mediated through a loading related effect on sub-periosteal expansion, BMD would be an unsatisfactory outcome measure in physical activity studies since it is inversely related to projected bone area. SM in contrast was associated with several measures of recent physical activity and relates more directly to the bending experienced by the proximal femur in response to a given load. These data are consistent with an effect of mechanical loading to regulate bone strength through an anabolic effect maximal in the subperiosteal cortex, where the highest loading-related strains are experienced.

Television viewing and low participation in vigorous recreation are independently associated with obesity and markers of cardiovascular disease risk: EPIC-Norfolk population-based study.

OBJECTIVE: This study describes the associations between sedentary behaviour (television viewing) and participation in vigorous recreational activity with obesity and with biomarkers of cardiovascular disease (CVD) risk profile. DESIGN: Cross-sectional analysis of the EPIC-Norfolk cohort study. SETTING: The study is a population-based study of participants living in Norfolk, UK. SUBJECTS: A total of 15 515 men and women aged between 45 and 74 y, recruited through General Practice lists, who completed the detailed physical activity questionnaire. RESULTS: Following exclusion of those with self-reported myocardial infarction, stroke and diabetes, 14 189 participants remained for the analysis. Self-reported television viewing was positively and participation in vigorous activity negatively associated with markers of obesity, blood pressure and plasma lipids. In multiple regression analysis, adjusting for age, alcohol, smoking, treatment for hypertension, vigorous and total physical activity, these associations remained significant. For women who participated in more than 1 h/week of vigorous activity and who watched fewer than 2 h of television each day, the adjusted mean body mass index was 1.92 kg/m(2) less than for women who reported participating in no vigorous activity and who watched more than 4 h of television each day (P<0.001). The equivalent figure for men was 1.44 kg/m(2) (P<0.001). In a similar analysis, with blood pressure as the outcome, mean diastolic blood pressure difference between the extreme groups of vigorous activity and television viewing was 3.6 mmHg in men (P<0.001) and 2.7 mmHg (P=0.001) in women. CONCLUSIONS: These data suggest that time spent participating in vigorous recreational physical activity and television viewing, an indicator of a sedentary lifestyle, are associated with obesity and markers of CVD disease risk independent of total reported physical activity. Whether these observations represent the true underlying aetiological relations or are a manifestation of the different precision with which the subdimensions of activity are measured remains uncertain.

Dietary intake of soybean protein and menstrual cycle length in pre-menopausal Singapore Chinese women.

BACKGROUND: Intake of soybean protein was associated with a reduced risk of breast cancer in a case-control study. It has also been demonstrated to increase menstrual cycle length in an experimental setting. OBJECTIVE: To ascertain whether the association of soybean protein intakes with menstrual cycle length persists in an uncontrolled community setting. DESIGN: Cross-sectional food frequency dietary survey, menstrual cycle survey and prospective collection of menstrual cycle data. SETTING: A hospital clinic and a nursing college. SUBJECTS: Two hundred menstruating women. RESULTS: An association (P = 0.034) of higher intakes of soybean protein with increased menstrual cycle length, as recorded by self report and by prospectively recording three consecutive cycles, was observed. The risk of menstrual cycle length being greater than the median, when comparing the upper quartile (8.7-35.2 g x day(-1)) of soybean intake and the lowest quartile (0.1-3.3 g x day(-1)) was double, and this approached statistical significance (OR = 2.02, 95% CI = 0.88-4.64 and OR = 1.93, 95% CI = 0.82-4.56 for self-reported cycle length and cycle length as recorded by diary, respectively). In terms of the absolute association with cycle length, subjects in the upper quartile of soybean intake demonstrated a cycle length 1-2 days longer than did subjects in the lowest quartile. CONCLUSIONS: It is likely that the association between dietary intake of soybean protein and length of menstrual cycle prevails in the community setting. This is shown using both self-reported cycle length and cycle length as recorded in a prospective diary.

Patterns of physical activity and ultrasound attenuation by heel bone among Norfolk cohort of European Prospective Investigation of Cancer (EPIC Norfolk): population based study.

OBJECTIVES: To study associations between patterns of physical activity and ultrasound attenuation by the heel bone in men and women. DESIGN: Cross sectional, population based study. SETTING: Norfolk. PARTICIPANTS: 2296 men and 2914 women aged 45-74 registered with general practices participating in European Prospective Investigation into Cancer (EPIC Norfolk). RESULTS: Self reported time spent in high impact physical activity was strongly and positively associated with ultrasound attenuation by the heel bone, independently of age, weight, and other confounding factors. Men who reported participating in >/=2 hours/week of high impact activity had 8.44 dB/MHz (95% confidence interval 4.49 to 12.40) or 9.5%, higher ultrasound attenuation than men who reported no activity of this type. In women, the difference in ultrasound attenuation between those reporting any high impact activity and those reporting none was 2.41 dB/MHz (0.45 to 4.37) or 3.4% higher. In women this effect was similar in size to that of an age difference of four years. Moderate impact activity had no effect. However, climbing stairs was strongly independently associated with ultrasound attenuation in women (0.64 dB/MHz (0.19 to 1.09) for each additional five flights of stairs). There was a significant negative association in women between time spent watching television or video and heel bone ultrasound attenuation, which decreased by 0.08 dB/MHz (0.02 to 0.14) for each additional hour of viewing a week. CONCLUSIONS: High impact physical activity is independently associated with ultrasound attenuation by the heel bone in men and women. As low ultrasound attenuation has been shown to predict increased risk of hip fracture, interventions to promote participation in high impact activities may help preserve bone density and reduce the risk of fracture. However, in older people such interventions may be inappropriate as they could increase the likelihood of falls.

Mammographic parenchymal patterns and risk of breast cancer at and after a prevalence screen in Singaporean women.

BACKGROUND: The objective of this study was to assess the effect of mammographic parenchymal patterns on risk of breast cancer detected at first screen or in the period following a negative screen. METHODS: The study utilizes a nested case-control design with 132 breast cancer patients detected at first screen (from a total of 29 193 screened) and 42 breast cancer patients detected in the period following the first screen. These patients were matched to 348 screened-negative controls. The mammograms were classified according to Tabar's classification for parenchymal pattern and statistical analysis was done by conditional logistic regression. RESULTS: The risk of breast cancer for women with Tabar pattern IV was significantly high when compared to the remaining patterns (odds ratio 2.59). Risk factors for Tabar pattern IV coincided largely with established risk factors for breast cancer. CONCLUSION: The study confirms the increased risk of breast cancer associated with Tabar pattern IV (approximately Wolfe pattern P2), in an Asian population. This pattern is associated with nulliparity and high educational status and is strongly associated with grade 3 cancers.