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Mammographic density (MD) phenotypes are strongly associated with breast cancer risk and highly heritable. In this GWAS meta-analysis of 24,192 women, we identify 31 MD loci at P  < 5 × 10 −8 , tripling the number known to 46. Seventeen identified MD loci also are associated with breast cancer risk in an independent meta-analysis ( P  < 0.05). Mendelian randomization analyses show that genetic estimates of dense area (DA), nondense area (NDA), and percent density (PD) are all significantly associated with breast cancer risk ( P  < 0.05). Pathway analyses reveal distinct biological processes involving DA, NDA and PD loci. These findings provide additional insights into the genetic basis of MD phenotypes and their associations with breast cancer risk. Mammographic density represents one the strongest predictors of breast cancer risk. Here the authors perform genome-wide association study meta-analysis of women screened with full-field digital mammography and identify 31 previously unreported loci associated with mammographic density phenotypes.

Recent studies have identified several single nucleotide polymorphisms (SNPs) in the population that are associated with variations in the risks of many different diseases including cancers such as breast, prostate and colorectal. For ovarian cancer, the known highly penetrant susceptibility genes (BRCA1 and BRCA2) are probably responsible for only 40% of the excess familial ovarian cancer risks, suggesting that other susceptibility genes of lower penetrance exist. We have taken a candidate approach to identifying moderate risk susceptibility alleles for ovarian cancer. To date, we have genotyped 340 SNPs from 94 candidate genes or regions, in up to 1,491 invasive epithelial ovarian cancer cases and 3,145 unaffected controls from three different population based studies from the UK, Denmark and USA. After adjusting for population stratification by genomic control, 18 SNPs (5.3%) were significant at the 5% level, and 5 SNPs (1.5%) were significant at the 1% level. The most significant association was for the SNP rs2107425, located on chromosome 11p15.5, which has previously been identified as a susceptibility allele for breast cancer from a genome wide association study (P-trend = 0.0012). When SNPs/genes were stratified into 7 different pathways or groups of validation SNPs, the breast cancer associated SNPs were the only group of SNPs that were significantly associated with ovarian cancer risk (P-heterogeneity = 0.0003; P-trend = 0.0028; adjusted (for population stratification) P-trend = 0.006). We did not find statistically significant associations when the combined data for all SNPs were analysed using an admixture maximum likelihood (AML) experiment-wise test for association (P-heterogeneity = 0.051; P-trend = 0.068). These data suggest that a proportion of the SNPs we evaluated were associated with ovarian cancer risk, but that the effect sizes were too small to detect associations with individual SNPs.

BRIP1 interacts with BRCA1 and functions in regulating DNA double strand break repair pathways. Germline BRIP1 mutations are associated with breast cancer and Fanconi anemia. Thus, common variants in the BRIP1 are candidates for breast and ovarian cancer susceptibility. We used a SNP tagging approach to evaluate the association between common variants (minor allele frequency>or=0.05) in BRIP1 and the risks of breast cancer and invasive ovarian cancer. 12 tagging SNPs (tSNPs) in the gene were identified and genotyped in up to 2,270 breast cancer cases and 2,280 controls from the UK and up to 1,513 invasive ovarian cancer cases and 2,515 controls from the UK, Denmark and USA. Genotype frequencies in cases and controls were compared using logistic regression. Two tSNPs showed a marginal significant association with ovarian cancer: Carriers of the minor allele of rs2191249 were at reduced risk compared with the common homozygotes (Odds Ratio (OR) = 0.90 (95% CI, 0.82-1.0), P-trend = 0.045) and the minor allele of rs4988344 was associated with increased risk (OR = 1.15 (95%CI, 1.02-1.30), P-trend = 0.02). When the analyses were restricted to serous ovarian cancers, these effects became slightly stronger. These results were not significant at the 5% level after adjusting for multiple testing. None of the tSNPs was associated with breast cancer. It is unlikely that common variants in BRIP1 contribute significantly to breast cancer susceptibility. The possible association of rs2191249 and rs4988344 with ovarian cancer risks warrant confirmation in independent case-control studies.

The article offers a study of the use of language in the fiction of Algerian-born writer, Amara Lakhous. It focuses on his two popular novels set in Rome, Clash of Civilizations over an Elevator at Piazza Vittorio (2008) and Divorce, Islamic Style (2012), in which the author describes changes in Italy and in definitions of Italian identity as the country undergoes the threefold process of migration, globalization and European integration. The article argues that the novels adopt a structure that displaces a single authored text and which suggests an authorship that is plurivoce, or plural voiced, and therefore able to overturn the marginalization of migrant voices. Exploring the author's foregrounding of linguistic practices - including voice, diction, and ethnic labelling - the article engages with Italy's history of regional, national, and transnational identities to argue that these novels are a postcolonial satire of the tenuous link between language and national belonging in Italy.

Are images and spectacles fundamental mediators of power relationships in the West? This book draws upon the language of cultural studies to investigate a contemporary hypothesis in the shifting ideological landscape of early modern Europe. Apparently aesthetic choices by artists may also have been the means to consolidate and subvert institutionalized or non-institutionalized bodies of power. Meanwhile, communities in Europe reacted to the intrinsic power of the image in literature and.

PurposeOne in six incident cancers in the U.S. is a second primary cancer (SPC). Although primary cancers vary considerably by race and ethnicity, little is known about the population-based occurrence of SPC across these groups.MethodsUsing Surveillance, Epidemiology, and End Results (SEER) 12 data and relative to the general population, we calculated standardized incidence ratios (SIRs) and 95% confidence intervals (CIs) for SPC among 2,457,756 Hispanics, non-Hispanic Asian American/Pacific Islanders (NHAAPI), non-Hispanic black (NHB), and non-Hispanic whites (NHW) cancer survivors aged 45 years or older when diagnosed with a first primary cancer (FPC) from 1992 to 2015.ResultsThe risk of second primary bladder cancer after first primary prostate cancer was higher than expected in Hispanic (SIR = 1.18, 95% CI: 1.01–1.38) and NHAAPI (SIR = 1.41, 95% CI: 1.20–1.65) men than NHB and NHW men. Among women with a primary breast cancer, Hispanic, NHAAPI, and NHB women had a nearly 1.5-fold higher risk of a second primary breast cancer, while NHW women had a 6% lower risk. Among men with prostate cancer whose SPC was diagnosed 2 to <12 months, NHB men were at higher risk for colorectal cancer and Hispanic and NHW men for non-Hodgkin’s lymphoma. In the same time frame for breast cancer survivors, Hispanic and NHAAPI women were significantly more likely than NHB and NHW women to be diagnosed with a second primary lung cancer.ConclusionFuture studies of SPC should investigate the role of shared etiologies, stage of diagnosis, treatment, and lifestyle factors after cancer survival across different racial and ethnic populations.

The article offers a study of the use of language in the fiction of Algerian-born writer, Amara Lakhous. It focuses on his two popular novels set in Rome, Clash of Civilizations over an Elevator at Piazza Vittorio (2008) and Divorce, Islamic Style (2012), in which the author describes changes in Italy and in definitions of Italian identity as the country undergoes the threefold process of migration, globalization and European integration. The article argues that the novels adopt a structure that displaces a single authored text and which suggests an authorship that is plurivoce, or plural voiced, and therefore able to overturn the marginalization of migrant voices. Exploring the author’s foregrounding of linguistic practices – including voice, diction, and ethnic labelling – the article engages with Italy’s history of regional, national, and transnational identities to argue that these novels are a postcolonial satire of the tenuous link between language and national belonging in Italy.

▪ Abstract  Assessing occupational exposures in community-based studies is a challenge for investigators because there are no standardized or validated approaches for collecting information regarding occupational history. The strengths and limitations of the methods available for assessing occupational exposures are reviewed. In community-based case-control studies, the prevalence of most chemical agents is low. The common sources of misclassification in these studies are addressed, as are strategies for dealing with misclassification bias. Methods to assess the presence and magnitude of differential reporting by cases and controls are outlined, together with analytic strategies to improve the classification of occupational exposures.

The COVID-19 pandemic exacerbated racism experienced by Asian Americans, especially women and older individuals. Little is known about how discriminatory experiences during the pandemic have influenced health behaviors among Asian Americans. Between 10/2021 and 6/2022, we surveyed 193 Asian American women in the San Francisco area. Participants were asked to report types of discrimination they experienced since March 2020. We explored bivariable associations of discrimination and changes in health behaviors and healthcare utilization. Most women were Chinese American (75%) and over 45-years-old (87%). The top three discriminatory experiences reported were being treated with less respect (60%), being treated unfairly at restaurants/stores (49%), and people acting as if they are better (47%). Chinese American women (vs. non-Chinese Asian American women) reported higher frequencies of being threatened/harassed (40% vs. 22%). Women who reported any discriminatory experience (vs. none) were more likely to report less physical exercise (42.7% vs. 26.3%) and canceling/rescheduling medical appointments (65.0% vs. 45.1%). Our findings begin to elucidate Asian American women’s experiences of discrimination since the pandemic and provide evidence of the harmful impacts of anti-Asian racism on health behaviors.

Women with low-grade ovarian serous carcinoma (LGSC) benefit from surgical treatment; however, the role of chemotherapy is controversial. We examined an international database through the Ovarian Cancer Association Consortium to identify factors that affect survival in LGSC. We performed a retrospective cohort analysis of patients with LGSC who had had primary surgery and had overall survival data available. We performed univariate and multivariate analyses of progression-free survival and overall survival, and generated Kaplan-Meier survival curves. Of the 707 patients with LGSC, 680 (96.2%) had available overall survival data. The patients' median age overall was 54 years. Of the 659 patients with International Federation of Obstetrics and Gynecology stage data, 156 (23.7%) had stage I disease, 64 (9.7%) had stage II, 395 (59.9%) had stage III, and 44 (6.7%) had stage IV. Of the 377 patients with surgical data, 200 (53.0%) had no visible residual disease. Of the 361 patients with chemotherapy data, 330 (91.4%) received first-line platinum-based chemotherapy. The median follow-up duration was 5.0 years. The median progression-free survival and overall survival were 43.2 months and 110.4 months, respectively. Multivariate analysis indicated a statistically significant impact of stage and residual disease on progression-free survival and overall survival. Platinum-based chemotherapy was not associated with a survival advantage. This multicentre analysis indicates that complete surgical cytoreduction to no visible residual disease has the most impact on improved survival in LGSC. This finding could immediately inform and change practice.