Background A recent association study identified a common variant (rs9790517) at 4q24 to be associated with breast cancer risk. Independent association signals and potential functional variants in this locus have not been explored. Methods We conducted a fine-mapping analysis in 55,540 breast cancer cases and 51,168 controls from the Breast Cancer Association Consortium. Results Conditional analyses identified two independent association signals among women of European ancestry, represented by rs9790517 (conditional p = 2.51 × 10−4; OR = 1.04; 95% CI 1.02–1.07) and rs77928427 (p = 1.86 × 10−4; OR = 1.04; 95% CI 1.02–1.07). Functional annotation using data from the Encyclopedia of DNA Elements (ENCODE) project revealed two putative functional variants, rs62331150 and rs73838678 in linkage disequilibrium (LD) with rs9790517 (r2 ≥ 0.90) residing in the active promoter or enhancer, respectively, of the nearest gene, TET2. Both variants are located in DNase I hypersensitivity and transcription factor binding sites. Using data from both The Cancer Genome Atlas (TCGA) and Molecular Taxonomy of Breast Cancer International Consortium (METABRIC), we showed that rs62331150 was associated with level of expression of TET2 in breast normal and tumor tissue. Conclusion Our study identified two independent association signals at 4q24 in relation to breast cancer risk and suggested that observed association in this locus may be mediated through the regulation of TET2. Impact Fine-mapping study with large sample size warranted for identification of independent loci for breast cancer risk.

INTRODUCTION: The ageing population means prescribing for chronic illnesses in older people is expected to rise. Comorbidities and compromised organ function may complicate prescribing and increase medication-related risks. Comorbid depression in older people is highly prevalent and complicates medication prescribing decisions. AIM: To determine the prevalence of potentially inappropriate medication use in a community-dwelling population of older adults with depressive symptoms. METHODS: The medications of 191 community-dwelling older people selected because of depressive symptoms for a randomised trial were reviewed and assessed using the modified version of the Beers’ Criteria. The association between inappropriate medication use and various population characteristics was assessed using Chi-square statistics and logistic regression analyses. RESULTS: The mean age was 81 (±4.3) years and 59% were women. The median number of medications used was 6 (range 1–21 medications). The most commonly prescribed potentially inappropriate medications were amitriptyline, dextropropoxyphene, quinine and benzodiazepines. Almost half (49%) of the participants were prescribed at least one potentially inappropriate medication; 29% were considered to suffer significant depressive symptoms (Geriatric Depression Scale =5) and no differences were found in the number of inappropriate medications used between those with and without significant depressive symptoms (Chi-square 0.005 p=0.54). DISCUSSION: Potentially inappropriate medication use, as per the modified Beers’ Criteria, is very common among community-dwelling older people with depressive symptoms. However, the utility of the Beers’ Criteria is lessened by lack of clinical correlation. Ongoing research to examine outcomes related to apparent inappropriate medication use is needed. KEYWORDS: Depression; depressive symptoms; inappropriate prescribing; older adults

Background The use of contraceptives is an essential public health concept that improves overall safe motherhood and infant health. Women empowerment has been reported to influence health behaviors in women. With recent efforts to increase access to contraceptive methods, uptake of the same remains a challenge in Cambodia. There are limited studies that have examined the role of women’s empowerment at both individual- and community- level on contraceptive use in Cambodia. This study examined the individual- and community-level factors associated with contraceptive use among Cambodian married women between 2005 and 2014. Methods Data from 2005, 2010, and 2014 Cambodia Demographic and Health Surveys were used to analyze 2211; 10,505; and 10,849 women, respectively. Multilevel binary and multinomial logistic regression models were applied to assess the association between individual- and community- level factors, and the use of contraceptive methods. Results The prevalence of using modern contraceptive methods increased over time (i.e., 29.0, 38.1, and 42.3% in 2005, 2010, and 2014, respectively). At the individual level, women who attained secondary and higher education were more likely to use any contraceptives [adjusted odds ratio (aOR) = 1.43, 95% confidence interval (CI) = 1.22–1.68, and aOR = 1.23, 95% CI = 1.05–1.44 in 2010 and 2014, respectively] compared with those with no formal education. Similarly, having a high workforce participation level was significantly associated with increased likelihood of using any contraceptive methods [aOR = 1.12, 95% CI = 1.00–1.26, aOR = 1.44, 95% CI = 1.29–1.60 and in 2010 and 2014, respectively]. Other factors such as age at first marriage, residence, and having a health insurance were associated with contraceptive use. The proportional change in variance showed that about 14.3% of total variations in the odds of contraceptive use across the communities were explained by both individual- and community-level factors. Moreover, the intraclass correlation showed that about 5.2% of the total variation remained unexplained even after adjustments. Conclusion Both individual- and community- level factors influenced contraceptive use in Cambodia. When designing programs to improve contraceptive use, contextual influences should be taken into account for the effectiveness of the programs.