| 1. |
- Bryazka, D., et al.
(author)
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Population-level risks of alcohol consumption by amount, geography, age, sex, and year: a systematic analysis for the Global Burden of Disease Study 2020
- 2022
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In: Lancet. - 0140-6736. ; 400:10347, s. 185-235
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Journal article (peer-reviewed)abstract
- Background The health risks associated with moderate alcohol consumption continue to be debated. Small amounts of alcohol might lower the risk of some health outcomes but increase the risk of others, suggesting that the overall risk depends, in part, on background disease rates, which vary by region, age, sex, and year. Methods For this analysis, we constructed burden-weighted dose-response relative risk curves across 22 health outcomes to estimate the theoretical minimum risk exposure level (TMREL) and non-drinker equivalence (NDE), the consumption level at which the health risk is equivalent to that of a non-drinker, using disease rates from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2020 for 21 regions, including 204 countries and territories, by 5-year age group, sex, and year for individuals aged 15-95 years and older from 1990 to 2020. Based on the NDE, we quantified the population consuming harmful amounts of alcohol. Findings The burden-weighted relative risk curves for alcohol use varied by region and age. Among individuals aged 15-39 years in 2020, the TMREL varied between 0 (95% uncertainty interval 0-0) and 0.603 (0.400-1.00) standard drinks per day, and the NDE varied between 0.002 (0-0) and 1.75 (0.698-4.30) standard drinks per day. Among individuals aged 40 years and older, the burden-weighted relative risk curve was J-shaped for all regions, with a 2020 TMREL that ranged from 0.114 (0-0.403) to 1.87 (0.500-3.30) standard drinks per day and an NDE that ranged between 0.193 (0-0.900) and 6.94 (3.40-8.30) standard drinks per day. Among individuals consuming harmful amounts of alcohol in 2020, 59.1% (54.3-65.4) were aged 15-39 years and 76.9% (7.0-81.3) were male. Interpretation There is strong evidence to support recommendations on alcohol consumption varying by age and location. Stronger interventions, particularly those tailored towards younger individuals, are needed to reduce the substantial global health loss attributable to alcohol. Copyright (C) 2022 The Author(s). Published by Elsevier Ltd.
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| 2. |
- Ikuta, K. S., et al.
(author)
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Global mortality associated with 33 bacterial pathogens in 2019: a systematic analysis for the Global Burden of Disease Study 2019
- 2022
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In: Lancet. - : Elsevier BV. - 0140-6736. ; 400:10369, s. 2221-2248
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Journal article (peer-reviewed)abstract
- Background Reducing the burden of death due to infection is an urgent global public health priority. Previous studies have estimated the number of deaths associated with drug-resistant infections and sepsis and found that infections remain a leading cause of death globally. Understanding the global burden of common bacterial pathogens (both susceptible and resistant to antimicrobials) is essential to identify the greatest threats to public health. To our knowledge, this is the first study to present global comprehensive estimates of deaths associated with 33 bacterial pathogens across 11 major infectious syndromes. Methods We estimated deaths associated with 33 bacterial genera or species across 11 infectious syndromes in 2019 using methods from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2019, in addition to a subset of the input data described in the Global Burden of Antimicrobial Resistance 2019 study. This study included 343 million individual records or isolates covering 11 361 study-location-years. We used three modelling steps to estimate the number of deaths associated with each pathogen: deaths in which infection had a role, the fraction of deaths due to infection that are attributable to a given infectious syndrome, and the fraction of deaths due to an infectious syndrome that are attributable to a given pathogen. Estimates were produced for all ages and for males and females across 204 countries and territories in 2019. 95% uncertainty intervals (UIs) were calculated for final estimates of deaths and infections associated with the 33 bacterial pathogens following standard GBD methods by taking the 2.5th and 97.5th percentiles across 1000 posterior draws for each quantity of interest. Findings From an estimated 13.7 million (95% UI 10.9-17.1) infection-related deaths in 2019, there were 7.7 million deaths (5.7-10.2) associated with the 33 bacterial pathogens (both resistant and susceptible to antimicrobials) across the 11 infectious syndromes estimated in this study. We estimated deaths associated with the 33 bacterial pathogens to comprise 13.6% (10.2-18.1) of all global deaths and 56.2% (52.1-60.1) of all sepsis-related deaths in 2019. Five leading pathogens-Staphylococcus aureus, Escherichia coli, Streptococcus pneumoniae, Klebsiella pneumoniae, and Pseudomonas aeruginosa-were responsible for 54.9% (52.9-56.9) of deaths among the investigated bacteria. The deadliest infectious syndromes and pathogens varied by location and age. The age-standardised mortality rate associated with these bacterial pathogens was highest in the sub-Saharan Africa super-region, with 230 deaths (185-285) per 100 000 population, and lowest in the high-income super-region, with 52.2 deaths (37.4-71.5) per 100 000 population. S aureus was the leading bacterial cause of death in 135 countries and was also associated with the most deaths in individuals older than 15 years, globally. Among children younger than 5 years, S pneumoniae was the pathogen associated with the most deaths. In 2019, more than 6 million deaths occurred as a result of three bacterial infectious syndromes, with lower respiratory infections and bloodstream infections each causing more than 2 million deaths and peritoneal and intra-abdominal infections causing more than 1 million deaths. Interpretation The 33 bacterial pathogens that we investigated in this study are a substantial source of health loss globally, with considerable variation in their distribution across infectious syndromes and locations. Compared with GBD Level 3 underlying causes of death, deaths associated with these bacteria would rank as the second leading cause of death globally in 2019; hence, they should be considered an urgent priority for intervention within the global health community. Strategies to address the burden of bacterial infections include infection prevention, optimised use of antibiotics, improved capacity for microbiological analysis, vaccine development, and improved and more pervasive use of available vaccines. These estimates can be used to help set priorities for vaccine need, demand, and development. Copyright (c) 2022 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license.
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| 9. |
- Couch, Fergus J., et al.
(author)
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Identification of four novel susceptibility loci for oestrogen receptor negative breast cancer
- 2016
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In: Nature Communications. - : NATURE PUBLISHING GROUP. - 2041-1723. ; 7:11375, s. 1-13
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Journal article (peer-reviewed)abstract
- Common variants in 94 loci have been associated with breast cancer including 15 loci with genome-wide significant associations (P<5 x 10(-8)) with oestrogen receptor (ER)-negative breast cancer and BRCA1-associated breast cancer risk. In this study, to identify new ER-negative susceptibility loci, we performed a meta-analysis of 11 genome-wide association studies (GWAS) consisting of 4,939 ER-negative cases and 14,352 controls, combined with 7,333 ER-negative cases and 42,468 controls and 15,252 BRCA1 mutation carriers genotyped on the iCOGS array. We identify four previously unidentified loci including two loci at 13q22 near KLF5, a 2p23.2 locus near WDR43 and a 2q33 locus near PPIL3 that display genome-wide significant associations with ER-negative breast cancer. In addition, 19 known breast cancer risk loci have genome-wide significant associations and 40 had moderate associations (P<0.05) with ER-negative disease. Using functional and eQTL studies we implicate TRMT61B and WDR43 at 2p23.2 and PPIL3 at 2q33 in ER-negative breast cancer aetiology. All ER-negative loci combined account for similar to 11% of familial relative risk for ER-negative disease and may contribute to improved ER-negative and BRCA1 breast cancer risk prediction.
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| 10. |
- Haiman, Christopher A., et al.
(author)
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A common variant at the TERT-CLPTM1L locus is associated with estrogen receptor-negative breast cancer
- 2011
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In: Nature Genetics. - : Springer Science and Business Media LLC. - 1546-1718 .- 1061-4036. ; 43:12, s. 61-1210
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Journal article (peer-reviewed)abstract
- Estrogen receptor (ER)-negative breast cancer shows a higher incidence in women of African ancestry compared to women of European ancestry. In search of common risk alleles for ER-negative breast cancer, we combined genome-wide association study (GWAS) data from women of African ancestry (1,004 ER-negative cases and 2,745 controls) and European ancestry (1,718 ER-negative cases and 3,670 controls), with replication testing conducted in an additional 2,292 ER-negative cases and 16,901 controls of European ancestry. We identified a common risk variant for ER-negative breast cancer at the TERT-CLPTM1L locus on chromosome 5p15 (rs10069690: per-allele odds ratio (OR) = 1.18 per allele, P = 1.0 x 10(-10)). The variant was also significantly associated with triple-negative (ER-negative, progesterone receptor (PR)-negative and human epidermal growth factor-2 (HER2)-negative) breast cancer (OR = 1.25, P = 1.1 x 10(-9)), particularly in younger women (<50 years of age) (OR = 1.48, P = 1.9 x 10(-9)). Our results identify a genetic locus associated with estrogen receptor negative breast cancer subtypes in multiple populations.
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| 11. |
- Lee, K. H., et al.
(author)
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Risk factors of COVID-19 mortality: a systematic review of current literature and lessons from recent retracted articles
- 2020
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In: European Review for Medical and Pharmacological Sciences. - : VERDUCI PUBLISHER. - 1128-3602. ; 24:24, s. 13089-13097
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Research review (peer-reviewed)abstract
- OBJECTIVE: Recently, two influential articles that reported the association of (hydroxy)chloroquine or angiotensin converting enzyme (ACE) inhibitors and coronavirus disease 2019 (COVID-19) mortality were retracted due to significant methodological issues. Therefore, we aimed to analyze the same clinical issues through an improved research method and to find out the differences from the retracted papers. We systematically reviewed pre-existing literature, and compared the results with those of the retracted papers to gain a novel insight. MATERIALS AND METHODS: We extracted common risk factors identified in two retracted papers, and conducted relevant publication search until June 26, 2020 in PubMed. Then, we analyzed the risk factors for COVID-19 mortality and compared them to those of the retracted papers. RESULTS: Our systematic review demonstrated that most demographic and clinical risk factors for COVID-19 mortality were similar to those of the retracted papers. However, while the retracted paper indicated that both (hydroxy)chloroquine monotherapy and combination therapy with macrolide were associated with higher risk of mortality, our study showed that only combination therapy of hydroxychloroquine and macrolide was associated with higher risk of mortality (odds ratio 2.33; 95% confidence interval 1.63-3.34). In addition, our study demonstrated that use of ACE inhibitors or angiotensin receptor blockers (ARBs) was associated with reduced risk of mortality (0.77; 0.65-0.91). CONCLUSIONS: When analyzing the same clinical issues with the two retracted papers through a systematic review of randomized controlled trials and relevant cohort studies. we found out that (hydroxy)chloroquine monotherapy was not associated with higher risk of mortality, and that the use of ACE inhibitors or ARBs was associated with reduced risk of mortality in COVID-19 patients.
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| 12. |
- Stevens, Kristen N, et al.
(author)
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19p13.1 is a triple negative-specific breast cancer susceptibility locus
- 2012
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In: Cancer Research. - 0008-5472 .- 1538-7445. ; 72, s. 1795-
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Journal article (peer-reviewed)abstract
- The 19p13.1 breast cancer susceptibility locus is a modifier of breast cancer risk in BRCA1 mutation carriers and is also associated with risk of ovarian cancer. Here we investigated 19p13.1 variation and risk of breast cancer subtypes, defined by estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor-2 (HER2) status, using 48,869 breast cancer cases and 49,787 controls from the Breast Cancer Association Consortium (BCAC). Variants from 19p13.1 were not associated with breast cancer overall or with ER-positive breast cancer but were significantly associated with ER-negative breast cancer risk [rs8170 Odds Ratio (OR)=1.10, 95% Confidence Interval (CI) 1.05 - 1.15, p=3.49 x 10-5] and triple negative (TN) (ER, PR and HER2 negative) breast cancer [rs8170 OR=1.22, 95% CI 1.13 - 1.31, p=2.22 x 10-7]. However, rs8170 was no longer associated with ER-negative breast cancer risk when TN cases were excluded [OR=0.98, 95% CI 0.89 - 1.07, p=0.62]. In addition, a combined analysis of TN cases from BCAC and the Triple Negative Breast Cancer Consortium (TNBCC) (n=3,566) identified a genome-wide significant association between rs8170 and TN breast cancer risk [OR=1.25, 95% CI 1.18 - 1.33, p=3.31 x 10-13]. Thus, 19p13.1 is the first triple negative-specific breast cancer risk locus and the first locus specific to a histological subtype defined by ER, PR, and HER2 to be identified. These findings provide convincing evidence that genetic susceptibility to breast cancer varies by tumor subtype and that triple negative tumors and other subtypes likely arise through distinct etiologic pathways.
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| 13. |
- Ahearn, Thomas U., et al.
(author)
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Common variants in breast cancer risk loci predispose to distinct tumor subtypes
- 2022
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In: Breast Cancer Research. - : Springer Nature. - 1465-5411 .- 1465-542X. ; 24:1
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Journal article (peer-reviewed)abstract
- BackgroundGenome-wide association studies (GWAS) have identified multiple common breast cancer susceptibility variants. Many of these variants have differential associations by estrogen receptor (ER) status, but how these variants relate with other tumor features and intrinsic molecular subtypes is unclear.MethodsAmong 106,571 invasive breast cancer cases and 95,762 controls of European ancestry with data on 173 breast cancer variants identified in previous GWAS, we used novel two-stage polytomous logistic regression models to evaluate variants in relation to multiple tumor features (ER, progesterone receptor (PR), human epidermal growth factor receptor 2 (HER2) and grade) adjusting for each other, and to intrinsic-like subtypes.ResultsEighty-five of 173 variants were associated with at least one tumor feature (false discovery rate < 5%), most commonly ER and grade, followed by PR and HER2. Models for intrinsic-like subtypes found nearly all of these variants (83 of 85) associated at p < 0.05 with risk for at least one luminal-like subtype, and approximately half (41 of 85) of the variants were associated with risk of at least one non-luminal subtype, including 32 variants associated with triple-negative (TN) disease. Ten variants were associated with risk of all subtypes in different magnitude. Five variants were associated with risk of luminal A-like and TN subtypes in opposite directions.ConclusionThis report demonstrates a high level of complexity in the etiology heterogeneity of breast cancer susceptibility variants and can inform investigations of subtype-specific risk prediction.
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| 14. |
- Kapoor, Pooja Middha, et al.
(author)
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Combined associations of a polygenic risk score and classical risk factors with breast cancer risk
- 2021
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In: Journal of the National Cancer Institute. - : Oxford University Press (OUP). - 0027-8874 .- 1460-2105. ; 113:3, s. 329-337
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Journal article (peer-reviewed)abstract
- We evaluated the joint associations between a new 313-variant PRS (PRS313) and questionnaire-based breast cancer risk factors for women of European ancestry, using 72 284 cases and 80 354 controls from the Breast Cancer Association Consortium. Interactions were evaluated using standard logistic regression and a newly developed case-only method for breast cancer risk overall and by estrogen receptor status. After accounting for multiple testing, we did not find evidence that per-standard deviation PRS313 odds ratio differed across strata defined by individual risk factors. Goodness-of-fit tests did not reject the assumption of a multiplicative model between PRS313 and each risk factor. Variation in projected absolute lifetime risk of breast cancer associated with classical risk factors was greater for women with higher genetic risk (PRS313 and family history) and, on average, 17.5% higher in the highest vs lowest deciles of genetic risk. These findings have implications for risk prevention for women at increased risk of breast cancer.
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| 15. |
- Kirchhoff, Tomas, et al.
(author)
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Breast cancer risk and 6q22.33 : combined results from Breast Cancer Association Consortium and Consortium of Investigators on Modifiers of BRCA1/2
- 2012
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In: PLOS ONE. - : Public library of science. - 1932-6203. ; 7:6
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Journal article (peer-reviewed)abstract
- Recently, a locus on chromosome 6q22.33 (rs2180341) was reported to be associated with increased breast cancer risk in the Ashkenazi Jewish (AJ) population, and this association was also observed in populations of non-AJ European ancestry. In the present study, we performed a large replication analysis of rs2180341 using data from 31,428 invasive breast cancer cases and 34,700 controls collected from 25 studies in the Breast Cancer Association Consortium (BCAC). In addition, we evaluated whether rs2180341 modifies breast cancer risk in 3,361 BRCA1 and 2,020 BRCA2 carriers from 11 centers in the Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA). Based on the BCAC data from women of European ancestry, we found evidence for a weak association with breast cancer risk for rs2180341 (per-allele odds ratio (OR) = 1.03, 95% CI 1.00-1.06, p = 0.023). There was evidence for heterogeneity in the ORs among studies (I(2) = 49.3%; p = <0.004). In CIMBA, we observed an inverse association with the minor allele of rs2180341 and breast cancer risk in BRCA1 mutation carriers (per-allele OR = 0.89, 95%CI 0.80-1.00, p = 0.048), indicating a potential protective effect of this allele. These data suggest that that 6q22.33 confers a weak effect on breast cancer risk.
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| 16. |
- Lee, S., et al.
(author)
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Neuropsychological adverse drug reactions of Remdesivir : analysis using VigiBase, the WHO global database of individual case safety report
- 2021
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In: European Review for Medical and Pharmacological Sciences. - : Verduci Publisher. - 1128-3602. ; 25:23, s. 7390-7397
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Journal article (peer-reviewed)abstract
- OBJECTIVE: Although remdesivir (GS-5734) has recently demonstrated clinical benefits against the pandemic outbreak of coronavirus disease 2019 (COVID-19), neuropsychological adverse reactions (ADRs) remain to be examined in real-world settings. Therefore, we aimed to identify and characterize the neuropsychological ADRs associated with remdesivir use.MATERIALS AND METHODS: We obtained data for this international pharmacovigilance cohort study from individual case safety reports (ICSRs) in a World Health Organization database (VigiBase) from the first report on remdesivir on February 17, 2020, until August 30, 2020 (n=1,403,532). ADRs reported to be relevant to remdesivir were compared with the full database by using a Bayesian neural network method to calculate the information component (IC).RESULTS: A total of 2,107 reported cases of neuropsychological ADRs suspected to be associated with remdesivir were identified from among all ICSRs in the database during the observation period. Although 108 neuropsychological ADRs (64 neurologic events and 44 psychologic events) were reported in association with the medication, no statistically significant pharmacovigilance signal could be detected; the ICO25 value was negative for all of the neuropsychological dysfunctions (anxiety [n=13, 0.62%], seizures [n=12, 0.57%], lethargy [n=6, 0.28%], agitation [n=5, 0.25%], cerebral infarction [n=3, 0.14%]. ischemic stroke [n=3, 0.14%], and hemiparesis [n=3, 0.14%]).CONCLUSIONS: Our study demonstrates that remdesivir, a novel drug applied to the treatment of COVID-19, does not have a significant association with adverse neurologic or psychiatric reactions in the real-world setting.
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| 17. |
- Middha, Pooja K., et al.
(author)
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A genome-wide gene-environment interaction study of breast cancer risk for women of European ancestry
- 2023
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In: Breast Cancer Research. - : BioMed Central (BMC). - 1465-5411 .- 1465-542X. ; 25:1
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Journal article (peer-reviewed)abstract
- Background Genome-wide studies of gene-environment interactions (GxE) may identify variants associated with disease risk in conjunction with lifestyle/environmental exposures. We conducted a genome-wide GxE analysis of similar to 7.6 million common variants and seven lifestyle/environmental risk factors for breast cancer risk overall and for estrogen receptor positive (ER +) breast cancer. Methods Analyses were conducted using 72,285 breast cancer cases and 80,354 controls of European ancestry from the Breast Cancer Association Consortium. Gene-environment interactions were evaluated using standard unconditional logistic regression models and likelihood ratio tests for breast cancer risk overall and for ER + breast cancer. Bayesian False Discovery Probability was employed to assess the noteworthiness of each SNP-risk factor pairs. Results Assuming a 1 x 10(-5) prior probability of a true association for each SNP-risk factor pairs and a Bayesian False Discovery Probability < 15%, we identified two independent SNP-risk factor pairs: rs80018847(9p13)-LINGO2 and adult height in association with overall breast cancer risk (ORint = 0.94, 95% CI 0.92-0.96), and rs4770552(13q12)-SPATA13 and age at menarche for ER + breast cancer risk (ORint = 0.91, 95% CI 0.88-0.94). Conclusions Overall, the contribution of GxE interactions to the heritability of breast cancer is very small. At the population level, multiplicative GxE interactions do not make an important contribution to risk prediction in breast cancer.
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| 18. |
- Choi, M. J., et al.
(author)
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Suicide associated with COVID-19 infection : an immunological point of view
- 2021
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In: European Review for Medical and Pharmacological Sciences. - Rome, Italy : VERDUCI PUBLISHER. - 1128-3602 .- 2284-0729. ; 25:20, s. 6397-6407
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Journal article (peer-reviewed)abstract
- OBJECTIVE: Coronavirus disease 2019 (COVID-19) is a pandemic and leading cause of death. Beyond the deaths directly caused by the virus and the suicides related to the psychological response to the dramatic changes as socioeconomic related to the pandemic, there might also be suicides related to the inflammatory responses of the infection. Infection induces inflammation as a cytokine storm, and there is an increasing number of studies that report a relationship between infection and suicide. MATERIALS AND METHODS: We searched the World Health Organization status report and the PubMed database for keywords (COVID-19, suicide, infection, inflammation, cytokines), and reviewed five cytokine pathways between suicide and inflammation using two meta-analyses and two observational studies starting from November 31, 2020, focusing on the relationship between suicide and inflammation by infection. First, we discussed existing evidence explaining the relationship between suicidal behaviors and inflammation. Second, we summarized the inflammatory features found in COVID-19 patients. Finally, we highlight the potential for these factors to affect the risk of suicide in COVID-19 patients. RESULTS: Patients infected with COVID-19 have high amounts of IL-1 beta, IFN-gamma, IP10, and MCP1, which may lead to Th1 cell response activation. Also, Th2 cytokines (e.g., IL-4 and IL-10) were increased in COVID-19 infection. In COVID-19 patients, neurological conditions, like headache, dizziness, ataxia, seizures, and others have been observed. CONCLUSIONS: COVID-19 pandemic can serve as a significant environmental factor contributing directly to increased suicide risk; the role of inflammation by an infection should not be overlooked.
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| 19. |
- Jeong, D. Y., et al.
(author)
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Empirical assessment of biases in cerebrospinal fluid biomarkers of alzheimer’s disease : An umbrella review and re-analysis of data from meta-analyses
- 2021
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In: European Review for Medical and Pharmacological Sciences. - : Verduci Publisher. - 1128-3602. ; 25:3, s. 1536-1547
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Research review (peer-reviewed)abstract
- OBJECTIVE: Alzheimer’s disease (AD) is a leading cause of years lived with disability in older age, and several cerebrospinal fluid (CSF) markers have been proposed in individual meta-analyses to be associated with AD but field-wide evaluation and scrutiny of the literature is not available. MATERIALS AND METHODS: We performed an umbrella review for the reported associations between CSF biomarkers and AD. Data from available meta-analyses were reanalyzed using both random and fixed effects models. We also estimated between-study heterogeneity, small-study effects, excess significance, and prediction interval. RESULTS: A total of 38 meta-analyses on CSF markers from 11 eligible articles were identified and reanalyzed. In 14 (36%) of the meta-analyses, the summary estimate and the results of the largest study showed non-concordant results in terms of statistical significance. Large heterogeneity (I2≥75%) was observed in 73% and small-study effects under Egger’s test were shown in 28% of CSF biomarkers. CONCLUSIONS: Our results suggest that there is an excess of statistically significant results and significant biases in the literature of CSF biomarkers for AD. Therefore, the results of CSF biomarkers should be interpreted with caution.
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| 20. |
- Mavaddat, Nasim, et al.
(author)
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Prediction of Breast Cancer Risk Based on Profiling With Common Genetic Variants
- 2015
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In: Journal of the National Cancer Institute. - : Oxford University Press (OUP). - 1460-2105 .- 0027-8874. ; 107:5, s. 036-036
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Journal article (peer-reviewed)abstract
- Background: Data for multiple common susceptibility alleles for breast cancer may be combined to identify women at different levels of breast cancer risk. Such stratification could guide preventive and screening strategies. However, empirical evidence for genetic risk stratification is lacking. Methods: We investigated the value of using 77 breast cancer-associated single nucleotide polymorphisms (SNPs) for risk stratification, in a study of 33 673 breast cancer cases and 33 381 control women of European origin. We tested all possible pair-wise multiplicative interactions and constructed a 77-SNP polygenic risk score (PRS) for breast cancer overall and by estrogen receptor (ER) status. Absolute risks of breast cancer by PRS were derived from relative risk estimates and UK incidence and mortality rates. Results: There was no strong evidence for departure from a multiplicative model for any SNP pair. Women in the highest 1% of the PRS had a three-fold increased risk of developing breast cancer compared with women in the middle quintile (odds ratio [OR] = 3.36, 95% confidence interval [CI] = 2.95 to 3.83). The ORs for ER-positive and ER-negative disease were 3.73 (95% CI = 3.24 to 4.30) and 2.80 (95% CI = 2.26 to 3.46), respectively. Lifetime risk of breast cancer for women in the lowest and highest quintiles of the PRS were 5.2% and 16.6% for a woman without family history, and 8.6% and 24.4% for a woman with a first-degree family history of breast cancer. Conclusions: The PRS stratifies breast cancer risk in women both with and without a family history of breast cancer. The observed level of risk discrimination could inform targeted screening and prevention strategies. Further discrimination may be achievable through combining the PRS with lifestyle/environmental factors, although these were not considered in this report.
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| 21. |
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| 22. |
- Lee, H. J., et al.
(author)
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Efficacy and safety of epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI) monotherapy for advanced EGFR-mutated non-small cell lung cancer: systematic review and meta-analysis
- 2021
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In: European Review for Medical and Pharmacological Sciences. - : VERDUCI PUBLISHER. - 1128-3602 .- 2284-0729. ; 25:20, s. 6232-6244
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Research review (peer-reviewed)abstract
- OBJECTIVE: It is controversial whether there is efficacy or safety benefit of epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI) in advanced EGFR-mutated non small cell lung cancer (NSCLC) compared to standard chemotherapy. We aim to assess the efficacy and safety of EGFR-TKIs compared to another chemotherapeutics in EGFR-mutated NSCLC. MATERIALS AND METHODS: Up to April 27th, 2020, PubMed, Embase, Medline, Scopus, Cochrane library, and ClinicalTrials.gov were searched for articles or trials meeting the inclusion criteria. After filtering, 230 eligible studies were initially identified. Data extraction followed PRISMA and included outcomes were progression-free survival (PFS), overall survival (OS), and severe adverse events (SAEs). Direct and indirect meta-analyses were generated in the context of log-linear mixed-effects models, with fixed effects for each relative comparison and random effects for each study. RESULTS: The results showed that EGFR-TKI therapy had improved PFS with a hazard ratio (HR) of 0.40 (95% CI: 0.36-0.44, p<0.001) compared to standard chemotherapy. Nevertheless, the EGFR-TKIs showed no benefit on OS (HR: 0.96, 95% CI: 0.83-1.10, p=0.556). In the analysis of adverse events, EGFR-TKIs had fewer SAEs than standard chemotherapy (HR: 0.29, 95% CI: 0.26-0.33, p<0.001). CONCLUSIONS: Our systemic review indicates that EGFR-TKI therapy has improved PFS, and reduced SAEs compared to standard chemotherapy in advanced EGFR-mutated NSCLC.
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| 23. |
- Cho, Kyuyeon, et al.
(author)
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Immunogenicity of COVID-19 vaccines in patients with diverse health conditions: A comprehensive systematic review
- 2022
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In: Journal of Medical Virology. - : WILEY. - 0146-6615 .- 1096-9071. ; 94:9, s. 4144-4155
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Research review (peer-reviewed)abstract
- It remains unclear how effective COVID-19 vaccinations will be in patients with weakened immunity due to diseases, transplantation, and dialysis. We conducted a systematic review comparing the efficacy of COVID-19 vaccination in patients with solid tumor, hematologic malignancy, autoimmune disease, inflammatory bowel disease, and patients who received transplantation or dialysis. A literature search was conducted twice using the Medline/PubMed database. As a result, 21 papers were included in the review, and seropositivity rate was summarized by specific type of disease, transplantation, and dialysis. When different papers studied the same type of patient group, a study with a higher number of participants was selected. Most of the solid tumor patients showed a seropositivity rate of more than 80% after the second inoculation, but a low seropositivity was found in certain tumors such as breast cancer. Research in patients with certain types of hematological malignancy and autoimmune diseases has also reported low seropositivity, and this may have been affected by the immunosuppressive treatment these patients receive. Research in patients receiving dialysis or transplantation has reported lower seropositivity rates than the general population, while all patients with inflammatory bowel disease have converted to be seropositive. Meta-analysis validating these results will be needed, and studies will also be needed on methods to protect patients with reduced immunity from COVID-19.
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| 24. |
- Garcia-Closas, Montserrat, et al.
(author)
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Heterogeneity of breast cancer associations with five susceptibility loci by clinical and pathological characteristics
- 2008
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In: PLoS genetics. - : Public Library of Science (PLoS). - 1553-7404. ; 4:4, s. e1000054-
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Journal article (peer-reviewed)abstract
- A three-stage genome-wide association study recently identified single nucleotide polymorphisms (SNPs) in five loci (fibroblast growth receptor 2 (FGFR2), trinucleotide repeat containing 9 (TNRC9), mitogen-activated protein kinase 3 K1 (MAP3K1), 8q24, and lymphocyte-specific protein 1 (LSP1)) associated with breast cancer risk. We investigated whether the associations between these SNPs and breast cancer risk varied by clinically important tumor characteristics in up to 23,039 invasive breast cancer cases and 26,273 controls from 20 studies. We also evaluated their influence on overall survival in 13,527 cases from 13 studies. All participants were of European or Asian origin. rs2981582 in FGFR2 was more strongly related to ER-positive (per-allele OR (95%CI) = 1.31 (1.27-1.36)) than ER-negative (1.08 (1.03-1.14)) disease (P for heterogeneity = 10(-13)). This SNP was also more strongly related to PR-positive, low grade and node positive tumors (P = 10(-5), 10(-8), 0.013, respectively). The association for rs13281615 in 8q24 was stronger for ER-positive, PR-positive, and low grade tumors (P = 0.001, 0.011 and 10(-4), respectively). The differences in the associations between SNPs in FGFR2 and 8q24 and risk by ER and grade remained significant after permutation adjustment for multiple comparisons and after adjustment for other tumor characteristics. Three SNPs (rs2981582, rs3803662, and rs889312) showed weak but significant associations with ER-negative disease, the strongest association being for rs3803662 in TNRC9 (1.14 (1.09-1.21)). rs13281615 in 8q24 was associated with an improvement in survival after diagnosis (per-allele HR = 0.90 (0.83-0.97). The association was attenuated and non-significant after adjusting for known prognostic factors. Our findings show that common genetic variants influence the pathological subtype of breast cancer and provide further support for the hypothesis that ER-positive and ER-negative disease are biologically distinct. Understanding the etiologic heterogeneity of breast cancer may ultimately result in improvements in prevention, early detection, and treatment.
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