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BackgroundBreast cancer is the most frequent cancer in women in industrialized countries. Lifestyle and environmental factors, particularly endocrine-disrupting pollutants, have been suggested to play a role in breast cancer risk. Current epidemiological studies, although not fully consistent, suggest a positive association of breast cancer risk with exposure to several International Agency for Research on Cancer Group 1 air-pollutant carcinogens, such as particulate matter, polychlorinated biphenyls (PCB), dioxins, Benzo[a]pyrene (BaP), and cadmium. However, epidemiological studies remain scarce and inconsistent. It has been proposed that the menopausal status could modify the relationship between pollutants and breast cancer and that the association varies with hormone receptor status. ObjectiveThe XENAIR project will investigate the association of breast cancer risk (overall and by hormone receptor status) with chronic exposure to selected air pollutants, including particulate matter, nitrogen dioxide (NO2), ozone (O3), BaP, dioxins, PCB-153, and cadmium. MethodsOur research is based on a case-control study nested within the French national E3N cohort of 5222 invasive breast cancer cases identified during follow-up from 1990 to 2011, and 5222 matched controls. A questionnaire was sent to all participants to collect their lifetime residential addresses and information on indoor pollution. We will assess these exposures using complementary models of land-use regression, atmospheric dispersion, and regional chemistry-transport (CHIMERE) models, via a Geographic Information System. Associations with breast cancer risk will be modeled using conditional logistic regression models. We will also study the impact of exposure on DNA methylation and interactions with genetic polymorphisms. Appropriate statistical methods, including Bayesian modeling, principal component analysis, and cluster analysis, will be used to assess the impact of multipollutant exposure. The fraction of breast cancer cases attributable to air pollution will be estimated. ResultsThe XENAIR project will contribute to current knowledge on the health effects of air pollution and identify and understand environmental modifiable risk factors related to breast cancer risk. ConclusionsThe results will provide relevant evidence to governments and policy-makers to improve effective public health prevention strategies on air pollution. The XENAIR dataset can be used in future efforts to study the effects of exposure to air pollution associated with other chronic conditions. International Registered Report Identifier (IRRID)DERR1-10.2196/15167

Cadmium, due to its estrogen‐like activity, has been suspected to increase the risk of breast cancer; however, epidemiological studies have reported inconsistent findings. We conducted a case–control study (4,059 cases and 4,059 matched controls) nested within the E3N French cohort study to estimate the risk of breast cancer associated with long‐term exposure to airborne cadmium pollution, and its effect according to molecular subtype of breast cancer (estrogen receptor negative/positive [ER−/ER+] and progesterone receptor negative/positive [PR−/PR+]). Atmospheric exposure to cadmium was assessed using a Geographic Information System‐based metric, which included subject's residence‐to‐cadmium source distance, wind direction, exposure duration and stack height. Adjusted odds ratios (OR) and 95% confidence intervals (CI) were estimated using conditional logistic regression. Overall, there was no significant association between cumulative dose of airborne cadmium exposure and the risk of overall, premenopausal and postmenopausal breast cancer. However, by ER and PR status, inverse associations were observed for ER− (ORQ5 vs. Q1 = 0.63; 95% CI: 0.41–0.95, ptrend = 0.043) and for ER−/PR− breast tumors (ORQ4 vs. Q1 = 0.62; 95% CI: 0.40–0.95, ORQ5 vs. Q1 = 0.68; 95% CI: 0.42–1.07, ptrend = 0.088). Our study provides no evidence of an association between exposure to cadmium and risk of breast cancer overall but suggests that cadmium might be related to a decreased risk of ER− and ER−/PR− breast tumors. These observations and other possible effects linked to hormone receptor status warrant further investigations. What's new? Cadmium is a common environmental contaminant that exerts estrogen‐like activity in human cells. While this activity suggests that cadmium might influence breast cancer risk, the relationship between cadmium exposure and breast cancer remains unclear. In this study, the authors employed a Geographic Information System (GIS)‐based metric to assess atmospheric cadmium exposure in women in France. No significant association was found between airborne cadmium and overall breast cancer risk. Risk varied, however, according to menopausal status and tumor hormone receptor status. Significant inverse associations were indicated for estrogen receptor‐negative breast cancers. Additional research is needed to assess cadmium exposure‐associated cancer risks. [ABSTRACT FROM AUTHOR]

Liver cancer (mostly hepatocellular carcinoma, HCC) is both common and highly lethal throughout Africa, in particular in western and middle Africa where HCC is the first cause of cancer death in men and the third in women. In these high-incidence areas, HCC develops mostly early (<50 years), with an aggressive clinical course and frequently without prior diagnosis of liver cirrhosis. The dynamics of African populations predict that the burden of liver cancers will be multiplied by three to four in the next decades unless effective prevention and therapy is achieved. This article outlines a path for significantly curbing the mortality of liver cancer in Africa by combining primary prevention, improved early detection and introduction of innovative and appropriate management strategies. [ABSTRACT FROM AUTHOR]

Reports of variable cancer penetrance in Li–Fraumeni syndrome (LFS) have raised questions regarding the prevalence of pathogenic germline TP53 variants. We previously reported higher‐than‐expected population prevalence estimates in sequencing databases composed of individuals unselected for cancer history. This study aimed to expand and further evaluate the prevalence of pathogenic and likely pathogenic germline TP53 variants in the gnomAD dataset (version r2.0.2, n = 138,632). Variants were selected and classified based on our previously published algorithm and compared with alternative estimates based on three different classification databases: ClinVar, HGMD, and the UMD_TP53 database. Conservative prevalence estimates of pathogenic and likely pathogenic TP53 variants were within the range of one carrier in 3,555–5,476 individuals. Less stringent classification increased the approximate prevalence to one carrier in every 400–865 individuals, mainly due to the inclusion of the controvertible p.N235S, p.V31I, and p.R290H variants. This study shows a higher‐than‐expected population prevalence of pathogenic and likely pathogenic germline TP53 variants even with the most conservative estimates. However, these estimates may not necessarily reflect the prevalence of the classical LFS phenotype, which is based upon family history of cancer. Comprehensive approaches are needed to better understand the interplay of germline TP53 variant classification, prevalence estimates, cancer penetrance, and LFS‐associated phenotype. gnomAD‐based analysis suggests that the population prevalence of pathogenic and likely pathogenic germline TP53 variants range from 1 carrier in 400 to 5,500 individuals due to differences in variant classification. These estimates may not necessarily reflect the prevalence of Li‐Fraumeni syndrome (LFS), which is based upon family history of cancer. We encourage comprehensive approaches to better understand the interplay of germline TP53 variant classification, prevalence estimates, cancer penetrance, and LFS‐associated phenotypes. [ABSTRACT FROM AUTHOR]