Fasting insulin and endogenous hormones in relation to premenopausal breast density (Canada).

PURPOSE: Mammographic breast density (BD) is associated with increased risk of breast cancer. This study asks which circulating metabolic and reproductive biomarkers are associated with BD, particularly dense breast area, in premenopausal women not taking exogenous hormones. METHODS: In a cross-sectional study, 299 premenopausal women aged 40-49 completed questionnaires, provided a fasting blood sample, had height, weight, percentage body fat, waist and hip measurements taken, and attended a screening mammogram. Multivariate linear regression was used to calculate adjusted means for percentage BD, absolute dense and non-dense area, across categories of covariates, adjusted for day of menstrual cycle, age, parity, body mass index, percentage body fat, and ethnicity. RESULTS: Fasting insulin levels were inversely associated, and insulin-like growth factor-binding protein 1 levels directly associated with percentage BD, but lost statistical significance after multivariate adjustment. Sex hormone-binding globulin levels were directly associated with percentage BD, still significant after multivariate adjustment (p = 0.03). A significant inverse dose-response association was observed between progesterone levels and dense area (p < 0.01). CONCLUSIONS: Breast density in premenopausal women seems unrelated or inversely related to insulin resistance, levels of insulin-like growth factor 1 and its binding proteins, and levels of sex steroids; therefore, the mechanism by which radiodensity on a mammogram is related to breast cancer risk remains unclear.

Breast cancer incidence and neighbourhood income.

BACKGROUND: In developed countries, women of higher socioeconomic status often have higher breast cancer incidence rates, compared with women of lower socioeconomic status. DATA AND METHODS: Data were extracted from the Canadian Cancer Registry for the 229,955 cases of adult female invasive breast cancer diagnosed from 1992 through 2004. Postal code at diagnosis was used to determine neighbourhood income quintile. Breast cancer incidence was examined by year, region, age and neighbourhood income quintile. Census data for 1991 on children ever born and British Columbia data for 2006 on first-time attendance at mammography screening were analyzed by neighbourhood income quintile. RESULTS: Residence in the lowest as opposed to the highest neighbourhood income quintile was associated with a 15% lower risk of being diagnosed with breast cancer. Higher income levels were associated with lower parity in 1991 and a higher prevalence of first-time screening mammography in British Columbia in 2006. INTERPRETATION: Canadian data support an association between the diagnosis of invasive breast cancer and neighbourhood income quintile. Parity and mammography screening may account for some differences in incidence.

Quality, quantity and harmony: the DataSHaPER approach to integrating data across bioclinical studies.

BACKGROUND: Vast sample sizes are often essential in the quest to disentangle the complex interplay of the genetic, lifestyle, environmental and social factors that determine the aetiology and progression of chronic diseases. The pooling of information between studies is therefore of central importance to contemporary bioscience. However, there are many technical, ethico-legal and scientific challenges to be overcome if an effective, valid, pooled analysis is to be achieved. Perhaps most critically, any data that are to be analysed in this way must be adequately 'harmonized'. This implies that the collection and recording of information and data must be done in a manner that is sufficiently similar in the different studies to allow valid synthesis to take place. METHODS: This conceptual article describes the origins, purpose and scientific foundations of the DataSHaPER (DataSchema and Harmonization Platform for Epidemiological Research; http://www.datashaper.org), which has been created by a multidisciplinary consortium of experts that was pulled together and coordinated by three international organizations: P³G (Public Population Project in Genomics), PHOEBE (Promoting Harmonization of Epidemiological Biobanks in Europe) and CPT (Canadian Partnership for Tomorrow Project). RESULTS: The DataSHaPER provides a flexible, structured approach to the harmonization and pooling of information between studies. Its two primary components, the 'DataSchema' and 'Harmonization Platforms', together support the preparation of effective data-collection protocols and provide a central reference to facilitate harmonization. The DataSHaPER supports both 'prospective' and 'retrospective' harmonization. CONCLUSION: It is hoped that this article will encourage readers to investigate the project further: the more the research groups and studies are actively involved, the more effective the DataSHaPER programme will ultimately be.

Facilitated "fast track" referral reduces time from abnormal screening mammogram to diagnosis.

BACKGROUND: The Screening Mammography Program of British Columbia (SMPBC) implemented voluntary, facilitated referral to diagnostic imaging ("Fast Track") after testing 5 interventions to reduce time from an abnormal screening mammogram to diagnosis. The purpose of this study was to compare time intervals for patients evaluated through the Fast Track process with patients who were not. METHODS: Data were extracted from the SMPBC database for women with abnormal screens conducted from January 1, 2003 to June 30, 2005 (N = 40,292). After exclusions, 39,607 screens were analyzed. Median and 90th percentile times were calculated from abnormal screen to diagnosis and for three subintervals: abnormal screen to notification, notification to first assessment, and first assessment to diagnosis. RESULTS: One third of abnormal screens were investigated through Fast Track imaging facilities. Overall, the median time from abnormal screen to diagnosis was 8 days faster for Fast Track compared with non-Fast Track. There was no clinically significant difference in time from abnormal screen to notification. The median time from notification to first assessment was 1.1 weeks (Fast Track) compared with 2.4 weeks (non-Fast Track), a reduction of 9 days or 54% in the interval targeted by the Fast Track strategy. The time interval distribution from first assessment to diagnosis was significantly different only for those having a core biopsy (average 3 days faster for Fast Track). INTERPRETATION: Facilitated referral to diagnostic imaging reduces average time from notification of abnormal screen to first assessment by more than half. Additional strategies are needed to address diagnostic investigation beyond initial imaging procedures.

A true screening environment for review of interval breast cancers: pilot study to reduce bias.

PURPOSE: To retrospectively assess the feasibility of an uninformed review process to evaluate interval breast cancers and to compare the number of false-negative cancers detected at uninformed review with the number detected at standard informed review. MATERIALS AND METHODS: Institutional review board approval was obtained for this retrospective study, and informed consent was waived. Mammograms showing interval cancer were included in the daily work of radiologists in a high-volume screening center. Each of three experienced radiologists read studies in the normal screening environment, without knowledge that identifiers had been changed to conceal the fact that studies were not current (ie, uninformed review). Results were compared with the standard review procedure, in which mammograms showing interval cancers were mixed with normal mammograms and read in a panel of 17-20 interval cancers per 80 normal studies by radiologists who were aware that they were participating in a review process (ie, informed review). RESULTS: Of 21 interval cancers, six (29%) were interpreted as positive more often by the informed radiologists than by the uninformed radiologists. For 14 (67%) cancers, there was no difference in detection rate between the two groups, and one cancer (5%) was seen by one of the uninformed radiologists but by none of the informed radiologists. The screening environment review process was found to be feasible at the low volumes tested. CONCLUSION: The number of false-negative cancers was higher in the informed review than in the uninformed review. This result suggests that bias exists with the informed review process.

Socioeconomic status and childhood solid tumor and lymphoma incidence in Canada.

The authors examined the relation between neighborhood income, as a measure of socioeconomic status, and childhood cancer. Incident cases of childhood solid tumor and lymphoma in 1985-2001 were identified from provincial cancer registries in Canada. Residential postal codes at the time of diagnosis were used to assign cases to census neighborhoods. Person-years at risk were determined from quintiles of population by neighborhood income, sex, and 5-year age group, constructed using census population data. Poisson regression was used to calculate incidence rate ratios across neighborhood income quintiles. Compared with the incidence rate in the richest income quintile, moderately lower rate ratios of 0.73 (95% confidence interval: 0.63, 0.86) and 0.84 (95% confidence interval: 0.69, 1.04) were observed, respectively, for carcinomas and renal tumors in the poorest income quintile. No association was found for other types of cancer. Although a potential relation between socioeconomic status and childhood cancer cannot be excluded, the overall pattern seems compatible with random variation.

Twenty-four-hour light exposure and melatonin levels among shift workers.

OBJECTIVES: We sought to measure melatonin levels and 24-hour light intensity exposure in health care workers over a 7-day period in natural occupational and residential settings. METHODS: Five office workers and 17 nurses working either days or rotating night and day shifts wore a device to record light intensity exposure for one or two 7-day periods, completed a questionnaire, and provided three saliva samples for melatonin. RESULTS: Rotating shift workers had irregular light exposure patterns and abnormal melatonin levels compared with those working days. In addition to lower-than-normal melatonin levels during sleep periods, rotating shift workers exhibited higher-than-normal melatonin levels on arising and during work. Self-reported years of shift work were correlated with measured melatonin and light. CONCLUSIONS: Rotating shift work is supported as a surrogate for exposure to light-at-night and circadian disruption.

Childhood leukemia and socioeconomic status in Canada.

BACKGROUND: Leukemia is one of the most common potentially fatal illnesses in children, and its causes are not well understood. Although socioeconomic status (SES) has been related to leukemia in some studies, this apparent association may be attributable to ascertainment or participation bias. This study was undertaken to determine whether there is a difference in incidence of childhood leukemia for different levels of SES, as measured by neighborhood income, in an unselected population case group. METHODS: All cases of childhood leukemia diagnosed in the years 1985-2001 were identified from population-based cancer registries in Canada. Postal codes for the place of residence at diagnosis were used to ascertain the census neighborhoods for cases. We constructed neighborhood-based income quintiles from census population data, and stratified the population at risk by sex and 5-year age groupings. Age-standardized incidence rates and 95% confidence intervals (CIs) were calculated. We used Poisson regression to compare incidence rate ratios (RRs) across income quintiles. RESULTS: A slightly lower relative risk of childhood leukemia was observed in the poorest quintile compared with the richest (RR = 0.87; 95% CI = 0.80-0.95). The lower risk in the poorest quintile was restricted to acute lymphoid leukemia (0.86; 0.78-0.95) and was strengthened slightly by restriction to urban areas (0.83; 0.74-0.93). CONCLUSIONS: This analysis suggests that high SES is a true risk factor for childhood leukemia and that inconsistent results from other studies may be related to differences in case ascertainment or study participation.

Insulin, macronutrient intake, and physical activity: are potential indicators of insulin resistance associated with mortality from breast cancer?

High levels of insulin have been associated with increased risk of breast cancer, and poorer survival after diagnosis. Data and sera were collected from 603 breast cancer patients, including information on diet and physical activity, medical history, family history, demographic, and reproductive risk factors. These data were analyzed to test the hypothesis that excess insulin and related factors are directly related to mortality after a diagnosis of breast cancer. The cohort was recruited from breast cancer patients treated at the British Columbia Cancer Agency between July 1991 and December 1992. Questionnaire and medical record data were collected at enrollment and outcomes were ascertained by linkage to the BC Cancer Registry after 10 years of follow-up. The primary outcome of interest was breast cancer-specific mortality (n = 112). Lifestyle data were analyzed using Cox proportional hazards regression models to relate risk factors to outcomes, controlling for potential confounders, such as age and stage at diagnosis. Data for biological variables were analyzed as a nested case-control study due to limited serum volumes, with at least one survivor from the same cohort as a control for each breast cancer death, matched on stage and length of follow-up. High levels of insulin were associated with poorer survival for postmenopausal women [odds ratio, 1.9; 95% confidence interval (CI), 0.7-6.6, comparing highest to lowest tertile, P trend = 0.10], while high dietary fat intake was associated with poorer survival for premenopausal women (relative risk, 4.8; 95% CI, 1.3-18.1, comparing highest to lowest quartile). Higher dietary protein intake was associated with better survival for all women (relative risk, 0.4; 95% CI, 0.2-0.8, comparing highest to lowest quartile).

Waist-to-hip ratio and breast cancer mortality.

High insulin levels have been associated with increased risk of breast cancer and poorer survival after a breast cancer diagnosis. Waist-to-hip ratio (WHR) is a marker for insulin resistance and hyperinsulinemia. In this study, the authors tested the hypothesis that elevated WHR is directly related to breast cancer mortality. For identification of modifiable factors affecting survival, data were collected on 603 patients with incident breast cancer who visited the Vancouver Cancer Centre of the British Columbia Cancer Agency (Vancouver, British Columbia, Canada) in 1991-1992, including body measurements and information on demographic, medical, reproductive, and dietary factors. These patients were followed for up to 10 years. Cox proportional hazards regression models were used to relate the variables to breast cancer mortality (n = 112). After adjustment for age, body mass index, family history, estrogen receptor (ER) status, tumor stage at diagnosis, and systemic treatment (chemotherapy or tamoxifen), WHR was directly related to breast cancer mortality in postmenopausal women (for highest quartile vs. lowest, relative risk = 3.3, 95% confidence interval: 1.1, 10.4) but not in premenopausal women (relative risk = 1.2, 95% confidence interval: 0.4, 3.4). Stratification according to ER status showed that the increased mortality was restricted to ER-positive postmenopausal women. Elevated WHR was confirmed as a predictor of breast cancer mortality, with menopausal status and ER status at diagnosis found to be important modifiers of that relation.

Carbohydrates and colorectal cancer risk among Chinese in North America.

Previous studies have analyzed total carbohydrate as a dietary risk factor for colorectal cancer (CRC) but obtained conflicting results, perhaps attributable in part to the embedded potential confounder, fiber. The aim of this study was to analyze the nonfiber ("effective") carbohydrate component (eCarb) separately and to test the hypothesis that effective carbohydrate consumption is directly related to CRC risk. The data (473 cases and 1192 controls) were from a large, multicenter, case-control study of Chinese residing in North America. Multivariate logistic regression was used to perform a secondary analysis controlling for age; sex; consumption of fat, fiber, calcium, and total kilocalories; body mass (Quetelet's) index; family history; education; and years in North America. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated to estimate risk among subgroups by sex and cancer site. A statistically significant positive association was observed between eCarb consumption and risk of CRC in both men (OR, 1.7 comparing highest with lowest tertile of eCarb consumption; 95% CI, 1.1-2.7) and women (OR, 2.7; 95% CI, 1.5-4.8). As expected, the ORs for total carbohydrate were somewhat lower than those for effective carbohydrate, but the differences were not large. A sex difference in risk by colorectal subsite was observed, with risk concentrated in the right colon for women (OR, 6.5; 95% CI, 2.4-18.4) and in the rectum for men (OR, 2.4; 95% CI, 1.2-4.8). These data indicate that increased eCarb and total carbohydrate consumption are both associated with increased risk of CRC in both sexes, and that among women, relative risk appears greatest for the right colon, whereas among men, relative risk appears greatest for the rectum.