A Systematic Review and Critical Assessment of Breast Cancer Risk Prediction Tools Incorporating a Polygenic Risk Score for the General Population.

Single nucleotide polymorphisms (SNPs) in the form of a polygenic risk score (PRS) have emerged as a promising factor that could improve the predictive performance of breast cancer (BC) risk prediction tools. This study aims to appraise and critically assess the current evidence on these tools. Studies were identified using Medline, EMBASE and the Cochrane Library up to November 2022 and were included if they described the development and/ or validation of a BC risk prediction model using a PRS for women of the general population and if they reported a measure of predictive performance. We identified 37 articles, of which 29 combined genetic and non-genetic risk factors using seven different risk prediction tools. Most models (55.0%) were developed on populations from European ancestry and performed better than those developed on populations from other ancestry groups. Regardless of the number of SNPs in each PRS, models combining a PRS with genetic and non-genetic risk factors generally had better discriminatory accuracy (AUC from 0.52 to 0.77) than those using a PRS alone (AUC from 0.48 to 0.68). The overall risk of bias was considered low in most studies. BC risk prediction tools combining a PRS with genetic and non-genetic risk factors provided better discriminative accuracy than either used alone. Further studies are needed to cross-compare their clinical utility and readiness for implementation in public health practices.

Assessment of evidence on reported non-genetic risk factors of congenital heart defects: the updated umbrella review.

BACKGROUND: Congenital heart defect (CHD) is the leading cause of birth defects globally, which results in a great disease burden. It is still imperative to detect the risk factors of CHD. This umbrella review aimed to comprehensively summarize the evidence and grade the evidence of the associations between non-genetic risk factors and CHD. METHODS: Databases including Medline, Embase, Web of Science, Cochrane Library, and four Chinese databases were searched from inception to 18 Jan 2022. The reference lists of systematic reviews (SR) and meta-analyses (MA) were screened, which aimed to explore the non-genetic risk factors of CHD. Subsequently, titles and abstracts of identified records and full texts of selected SR/MA were screened by two independent reviewers based on predefined eligibility criteria. A priori developed extraction form was used to abstract relative data following the PRISMA 2020 and MOOSE guidelines. The risk of bias was assessed with the AMSTAR2 instrument. Data were synthesized using fixed-effects and random-effects meta-analyses, respectively. Finally, the evidence on the association of non-genetic risk factors and CHD was graded using Ioannidis's five-class evidence grade. RESULTS: A total of 56 SRs, encompassing 369 MAs, were identified. The risk factors included relative factors on air pollution, reproductive-related factors, parental age and BMI, parental life habits, working and dwelling environment, maternal drug exposure, and maternal disease. Based on AMSTAR2 criteria, only 16% (9/56) of SRs were classified as "Moderate". One hundred and two traceable positive association MAs involving 949 component individual studies were included in further analysis and grading of evidence. Family genetic history, number of abortions, maternal obesity, especially moderate or severe obesity, decoration materials, harmful chemicals, noise during pregnancy, folic acid supplementation, SSRIs, SNRIs, any antidepressants in the first trimester, maternal DM (including both PGDM and GDM), and gestational hypertension were convincing and highly suggestive factors for CHD. After sensitivity analyses based on cohort studies, some grades of evidence changed. CONCLUSION: The present umbrella review will provide evidence-based information for women of childbearing age before or during pregnancy to prevent CHD. In addition, sensitivity analysis based on cohort studies showed the changed evidence levels. Therefore, future SR/MA should concern the sensitivity analysis based on prospective birth cohort studies and case-control studies.

Aspectos clínicos y epidemiológicos en pacientes con cáncer de pulmón en un servicio de neumología / Clinical and epidemiological aspects in patients with lung cancer in a pneumology service

Se realizó un estudio descriptivo y transversal de 125 pacientes con cáncer de pulmón, ingresados y diagnosticados en el Servicio de Neumología del Hospital General Docente Dr Juan Bruno Zayas Alfonso de Santiago de Cuba, de enero de 2015 a octubre de 2016, con vistas a caracterizarles según variables clínicas y epidemiológicas de interés, además de factores de riesgo genéticos y no genéticos, independientemente de las características histológicas y el estadio clínico del proceso neoplásico. Entre los resultados preponderantes figuraron el sexo masculino y el grupo etario de 51-69 años -- aunque fue evidente el incremento del número de féminas y de pacientes en las edades más jóvenes de la vida --, igualmente la broncoscopia como método diagnóstico, la localización en el pulmón derecho, el adenocarcinoma como variedad histológica, el tabaquismo entre los factor de riesgo no genético y el parentesco de primer grado en los factores genéticos. La mayoría de los afectados presentaban menos de un año de evolución y un elevado porcentaje correspondía al estadio IV de la enfermedad.

A descriptive and cross-sectional study of 125 patients with lung cancer, admitted and diagnosed in the Pneumology Service of Dr Juan Bruno Zayas Alfonso Teaching General Hospital in Santiago de Cuba was carried out from January, 2015 to October, 2016, aimed at characterizing them according to clinical and epidemiological variables of interest, besides genetic and non genetic risk factors, independently from the histological characteristics and the clinical stage of the neoplastic process. Among the predominant results there were the male sex and the age group 51-69, although the increment of the females and of patients in the youngest ages in the life was evident --, equally the bronchoscopy as diagnostic method, the localization in the right lung, the adenocarcinoma as histological variety, smoking habit among non genetic risk factors and the first degree relation in the genetic factors. Most of the affected patients presented a clinical course shorter than a year and a high percentage were in the stage IV of the disease.

A statewide investigation of geographic lung cancer incidence patterns and radon exposure in a low-smoking population.

BACKGROUND: Lung cancer is the leading cause of cancer-related mortality in Utah despite having the nation's lowest smoking rate. Radon exposure and differences in lung cancer incidence between nonmetropolitan and metropolitan areas may explain this phenomenon. We compared smoking-adjusted lung cancer incidence rates between nonmetropolitan and metropolitan counties by predicted indoor radon level, sex, and cancer stage. We also compared lung cancer incidence by county classification between Utah and all SEER sites. METHODS: SEER*Stat provided annual age-adjusted rates per 100,000 from 1991 to 2010 for each Utah county and all other SEER sites. County classification, stage, and sex were obtained from SEER*Stat. Smoking was obtained from Environmental Public Health Tracking estimates by Ortega et al. EPA provided low (< 2 pCi/L), moderate (2-4 pCi/L), and high (> 4 pCi/L) indoor radon levels for each county. Poisson models calculated overall, cancer stage, and sex-specific rates and p-values for smoking-adjusted and unadjusted models. LOESS smoothed trend lines compared incidence rates between Utah and all SEER sites by county classification. RESULTS: All metropolitan counties had moderate radon levels; 12 (63%) of the 19 nonmetropolitan counties had moderate predicted radon levels and 7 (37%) had high predicted radon levels. Lung cancer incidence rates were higher in nonmetropolitan counties than metropolitan counties (34.8 vs 29.7 per 100,000, respectively). Incidence of distant stage cancers was significantly higher in nonmetropolitan counties after controlling for smoking (16.7 vs 15.4, p = 0.02*). Incidence rates in metropolitan, moderate radon and nonmetropolitan, moderate radon counties were similar. Nonmetropolitan, high radon counties had a significantly higher incidence of lung cancer compared to nonmetropolitan, moderate radon counties after adjustment for smoking (41.7 vs 29.2, p < 0.0001*). Lung cancer incidence patterns in Utah were opposite of metropolitan/nonmetropolitan trends in other SEER sites. CONCLUSION: Lung cancer incidence and distant stage incidence rates were consistently higher in nonmetropolitan Utah counties than metropolitan counties, suggesting that limited access to preventative screenings may play a role in this disparity. Smoking-adjusted incidence rates in nonmetropolitan, high radon counties were significantly higher than moderate radon counties, suggesting that radon was also major contributor to lung cancer in these regions. National studies should account for geographic and environmental factors when examining nonmetropolitan/metropolitan differences in lung cancer.