Intrauterine devices and endometrial cancer risk : a pooled analysis of the Epidemiology of Endometrial Cancer Consortium

Intrauterine devices (IUDs), long-acting and reversible contraceptives, induce a number of immunological and biochemical changes in the uterine environment that could affect endometrial cancer (EC) risk. We addressed this relationship through a pooled analysis of data collected in the Epidemiology of Endometrial Cancer Consortium. We combined individual-level data from 4 cohort and 14 case-control studies, in total 8,801 EC cases and 15,357 controls. Using multivariable logistic regression, we estimated pooled odds ratios (pooled-ORs) and 95% confidence intervals (CIs) for EC risk associated with ever use, type of device, ages at first and last use, duration of use and time since last use, stratified by study and adjusted for confounders. Ever use of IUDs was inversely related to EC risk (pooled-OR = 0.81, 95% CI = 0.74-0.90). Compared with never use, reduced risk of EC was observed for inert IUDs (pooled-OR = 0.69, 95% CI = 0.58-0.82), older age at first use (≥35 years pooled-OR = 0.53, 95% CI = 0.43-0.67), older age at last use (≥45 years pooled-OR = 0.60, 95% CI = 0.50-0.72), longer duration of use (≥10 years pooled-OR = 0.61, 95% CI = 0.52-0.71) and recent use (within 1 year of study entry pooled-OR = 0.39, 95% CI = 0.30-0.49). Future studies are needed to assess the respective roles of detection biases and biologic effects related to foreign body responses in the endometrium, heavier bleeding (and increased clearance of carcinogenic cells) and localized hormonal changes

Estimating the current and future cancer burden in Canada: Methodological framework of the Canadian population attributable risk of cancer (ComPARe) study

Introduction The Canadian Population Attributable Risk of Cancer project aims to quantify the number and proportion of cancer cases incident in Canada, now and projected to 2042, that could be prevented through changes in the prevalence of modifiable exposures associated with cancer. The broad risk factor categories of interest include tobacco, diet, energy imbalance, infectious diseases, hormonal therapies and environmental factors such as air pollution and res

Identification of nine new susceptibility loci for endometrial cancer

Endometrial cancer is the most commonly diagnosed cancer of the female reproductive tract in developed countries. Through genome-wide association studies (GWAS), we have previously identified eight risk loci for endometrial cancer. Here, we present an expanded meta-analysis of 12,906 endometrial cancer cases and 108,979 controls (including new genotype data for 5624 cases) and identify nine novel genome-wide significant loci, including a locus on 12q24.12 previously identified by meta-GWAS of endometrial and colorectal cancer. At five loci, expression quantitative trait locus (eQTL) analyses identify candidate causal genes; risk alleles at two of these loci associate with decreased expression of genes, which encode negative regulators of oncogenic signal transduction proteins (SH2B3 (12q24.12) and NF1 (17q11.2)). In summary, this study has doubled the number of known endometrial cancer risk loci and revealed candidate causal genes for future study

Female chromosome X mosaicism is age-related and preferentially affects the inactivated X chromosome

To investigate large structural clonal mosaicism of chromosome X, we analysed the SNP microarray intensity data of 38,303 women from cancer genome-wide association studies (20,878 cases and 17,425 controls) and detected 124 mosaic X events42Mb in 97 (0.25%) women. Here we show rates for X-chromosome mosaicism are four times higher than mean autosomal rates; X mosaic events more often include the entire chromosome and participants with X events more likely harbour autosomal mosaic events. X mosaicism frequency increases with age (0.11% in 50-year olds; 0.45% in 75-year olds), as reported for Y and autosomes. Methylation array analyses of 33 women with X mosaicism indicate events preferentially involve the inactive X chromosome. Our results provide further evidence that the sex chromosomes undergo mosaic events more frequently than autosomes, which could have implications for understanding the underlying mechanisms of mosaic events and their possible contribution to risk for chronic diseases

Dietary patterns with combined and site-specific cancer incidence in Alberta’s Tomorrow Project cohort

Public Health and primary carePrevention, Population and Disease management (PrePoD

Physical activity in relation to mammographic density in the dutch prospect-European prospective investigation into cancer and nutrition cohort.

BACKGROUND: Evidence accumulates that physical inactivity is one of the few modifiable risk factors for breast cancer. The mechanism through which physical inactivity affects breast cancer risk is not clear. The study aim was to investigate the association between physical activity and breast density because mammographic density is strongly associated with breast cancer risk. METHODS: We did a cross-sectional study in 620 women, of ages 49 to 68 years and participants of the Dutch Prospect-European Prospective Investigation into Cancer and Nutrition cohort. A self-administered questionnaire was used to obtain information on duration and intensity of physical activity (recreational, household, and occupational) during the year preceding study recruitment. A total activity index (inactive, moderately inactive, moderately active, and active) was estimated by combining all activity types. Percent and absolute breast density were determined on screening mammograms using a computer-aided method. Multivariate linear regression was used to examine the association between physical activity and breast density. RESULTS: Mean percent density was 35.3% [95% confidence interval (95% CI), 31.8-38.8] for the inactive category compared with 36.1% (95% CI, 33.0-39.2) for the active category. Mean absolute density values for the inactive and active category were 45.8 cm(2) (95% CI, 40.9-50.7) and 42.6 cm(2) (95% CI, 38.3-47.0), respectively. Subgroup analysis for postmenopausal women showed similar results, as did separate analyses for recreational and household activity. CONCLUSIONS: The result does not support a relation between current physical activity and mammographic density in postmenopausal women

Physical activity in relation to mammographic density in the dutch prospect-European prospective investigation into cancer and nutrition cohort.

BACKGROUND: Evidence accumulates that physical inactivity is one of the few modifiable risk factors for breast cancer. The mechanism through which physical inactivity affects breast cancer risk is not clear. The study aim was to investigate the association between physical activity and breast density because mammographic density is strongly associated with breast cancer risk. METHODS: We did a cross-sectional study in 620 women, of ages 49 to 68 years and participants of the Dutch Prospect-European Prospective Investigation into Cancer and Nutrition cohort. A self-administered questionnaire was used to obtain information on duration and intensity of physical activity (recreational, household, and occupational) during the year preceding study recruitment. A total activity index (inactive, moderately inactive, moderately active, and active) was estimated by combining all activity types. Percent and absolute breast density were determined on screening mammograms using a computer-aided method. Multivariate linear regression was used to examine the association between physical activity and breast density. RESULTS: Mean percent density was 35.3% [95% confidence interval (95% CI), 31.8-38.8] for the inactive category compared with 36.1% (95% CI, 33.0-39.2) for the active category. Mean absolute density values for the inactive and active category were 45.8 cm(2) (95% CI, 40.9-50.7) and 42.6 cm(2) (95% CI, 38.3-47.0), respectively. Subgroup analysis for postmenopausal women showed similar results, as did separate analyses for recreational and household activity. CONCLUSIONS: The result does not support a relation between current physical activity and mammographic density in postmenopausal women

Indoor tanning and skin cancer in Canada: A meta-analysis and attributable burden estimation

Background: Consistent epidemiologic and experimental studies have demonstrated that UV-emitting tanning devices cause melanoma and non-melanoma skin cancer. The purpose of this study was to estimate the relative risk of skin cancer associated with the use of indoor tanning devices relevant to Canada, to estimate the proportion and number of skin cancers in Canada in 2015 that were attributable to indoor tanning, and to explore differences by age and sex. Methods: Skin cancer cases attributable to the use of an indoor tanning devices were estimated using Levin's population attributable risk (PAR) formula. Relative risks for skin cancer subtypes that were relevant to Canada were estimated through meta-analyses and prevalence of indoor tanning was estimated from the 2006 National Sun Survey. Age- and sex-specific melanoma data for 2015 were obtained from the Canadian Cancer Registry, while estimated NMSC incidence data were obtained from the 2015 Canadian Cancer Statistics report. Results: Ever use of indoor tanning devices was associated with relative risks of 1.38 (95% CI 1.22–1.58) for melanoma, 1.39 (1.10–1.76) for basal cell carcinoma (BCC), and 1.49 (1.23–1.80) for squamous cell carcinoma (SCC). Overall, 7.0% of melanomas, 5.2% of BCCs, and 7.5% of SCCs in 2015 were attributable to ever of indoor tanning devices. PARs were higher for women and decreased with age. Conclusion: Indoor tanning contributes to a considerable burden of skin cancer in Canada. Strategies aimed at reducing use should be increased and a total ban or restrictions on use and UV-int

Estimates of the current and future burden of cancer attributable to active and passive tobacco smoking in Canada

Although previous studies have examined the burden of cancer attributable to tobacco smoking, updated estimates are needed given the dramatic changes in smoking behaviours over the last 20 years. In this study, we estimate the proportion of cancer cases in 2015 attributable to past tobacco smoking and passive exposure in Canada and the proportion of cancers in the future that could be prevented through the implementation of interventions targeted at reducing tobacco use. Data from the Canadian Community Health Survey (2003) were used to estimate the prevalence of active tobacco smoking and passive exposure. Population attributable risk estimates were employed to estimate the proportion of cancers attributable to tobacco in 2015. The prevalence of active tobacco smoking and passive exposure was projected to 2032 and cancer incidence was projected from 2016 to 2042 to estimate the future burden of cancer attributable to tobacco. In 2003, 30% and 24% of Canadians were former and current smoker, respectively and 24