Cancer Risk Research Articles

Unrecognised actionability for breast cancer risk variants identified in a national-level review of Australian familial cancer centres.

Breast cancer remains a significant global health challenge. In Australia, the adoption of publicly-funded multigene panel testing for eligible cancer patients has increased accessibility to personalised care, yet has also highlighted the increasing prevalence of variants of uncertain significance (VUS), complicating clinical decision-making. This project aimed to explore the spectrum and actionability of breast cancer VUS in Australian familial cancer centers (FCCs). Leveraging data from 11 FCCs participating in the Inherited Cancer Connect database, we retrieved VUS results from 1472 patients. Through ClinVar crosschecks and application of gene-specific ACMG/AMP guidelines, we showed the potential for reclassification of 4% of unique VUS as pathogenic or likely pathogenic, and 80% as benign or likely benign. Surveys conducted with FCCs and diagnostic laboratories described current practices and challenges in variant reclassifications, highlighting resource constraints preventing periodic VUS review and notifications from the laboratories to the FCCs. Our study suggests there are benefits to routine VUS review and reclassification, particularly in publicly-funded healthcare systems. Future research should focus on assessing the clinical impact and cost-effectiveness of implementing routine variant review practices, alongside efforts to enhance communication between FCCs and laboratories.

Identification of an additive interaction using parameter regularization and model selection in epidemiology

Background In epidemiology, indicators such as the relative excess risk due to interaction (RERI), attributable proportion (AP), and synergy index (S) are commonly used to assess additive interactions between two variables. However, the results of these indicators are sometimes inconsistent in real world applications and it may be difficult to draw conclusions from them. Method Based on the relationship between the RERI, AP, and S, we propose a method with consistent results, which are achieved by constraining $e^{\theta_3}-e^{\theta_1}-e^{\theta_2}+1=0$, and the interpretation of the results is simple and clear. We present two pathways to achieve this end: one is to complete the constraint by adding a regular penalty term to the model likelihood function; the other is to use model selection. Result Using simulated and real data, our proposed methods effectively identified additive interactions and proved to be applicable to real-world data. Simulations were used to evaluate the performance of the methods in scenarios with and without additive interactions. The penalty term converged to 0 with increasing λ, and the final models matched the expected interaction status, demonstrating that regularized estimation could effectively identify additive interactions. Model selection was compared with classical methods (delta and bootstrap) across various scenarios with different interaction strengths, and the additive interactions were closely observed and the results aligned closely with bootstrap results. The coefficients in the model without interaction adhered to a simplifying equation, reinforcing that there was no significant interaction between smoking and alcohol use on oral cancer risk. Conclusion In summary, the model selection method based on the Hannan-Quinn criterion (HQ) appears to be a competitive alternative to the bootstrap method for identifying additive interactions. Furthermore, when using RERI, AP, and S to assess the additive interaction, the results are more consistent and the results are simple and easy to understand.

A dose-response meta-analysis of the relationship between number of pregnancies and risk of gynecological cancers.

Despite several investigations, the association between the number of pregnancies and gynecological cancers remains inconclusive. To address this issue, we conducted a dose-response meta-analysis of observational studies. We searched PubMed, Web of Science, and Scopus databases up to Jun 8, 2023, to identify observational studies that examined the association between the number of pregnancies and gynecologic cancers. To assess the heterogeneity across studies, we used the χ2 test and I2 statistics. We also explored the possibility of publication bias using Begg's and Egger's tests. The overall effect sizes were reported as odds ratios (ORs) with a 95% confidence interval (CI) using a random-effects model. Out of the 87,255 studies initially identified, a total of 101 studies involving 8,230,754 participants were included in the final meta-analysis. Our analysis revealed a positive trend between the number of pregnancies and cervical cancer; however, this association was not found to be statistically significant except for fifth pregnancy. Conversely, our findings showed a significant decreasing trend between the number of pregnancies and the risk of endometrial and ovarian cancers. There was insufficient evidence to establish a relationship between the number of pregnancies and the risk of vaginal, vulvar, and fallopian tube cancers. Our study found a positive trend between the number of pregnancies and cervical cancer and a significant decreasing trend between the number of pregnancies and endometrial and ovarian cancers. These findings may have implications for counseling women about their reproductive health and the potential risks and benefits of pregnancy.

Air pollution by BTEX and the related health risks due to the tobacco smoke, a systematic review

BTEX is a group of hazardous chemical compounds that include benzene, toluene, ethylbenzene, and xylene. The indoor concentration of BTEX is mostly influenced by tobacco smoking, the region within the house, and seasonal variations. This systematic review analyzed studies on BTEX concentrations in indoor air, using data from Google Scholar, Science Direct, and Springer from 2010 to 2020, and performed statistical analysis with R after thorough data extraction and evaluation. Duplicate studies were removed, and disagreements during the article selection process were resolved by a third reviewer. Out of the 1351 articles obtained from the keyword search, only 13 were eventually selected for this study. The most abundant compound found in houses among BTEX was toluene, with a concentration of 13.80±16.50 µg/m3. The results indicated that the concentration of ƩBTEX in houses where smoking occurred was lower than in houses where no smoking occurred (18.52 vs. 27.66 µg/m3); However, the concentration of benzene in smoking houses was higher than in non-smoking houses (7.17±9.42 vs. 2.65±3.77 µg/m3, unpaired Wilcoxon test: p>0.05). The concentration of BTEX in houses was substantially lower than that in cafes (21.10±31.10 vs. 15,100±9740 µg/m3, unpaired Wilcoxon test: p<0.05). The urban region had the most significant accumulation of all BTEXs, with the industrial and rural sectors following suit. The findings indicated that the average concentration of BTEX in warm months (such as spring and summer) were higher than in cold months (such as fall and winter) within houses (28.50±44.30 vs. 8.60±7.77 µg/m3, unpaired Wilcoxon test: p>0.05). The findings indicated that the Cancer Risk (CR) associated with houses (3.11×10-6) and cafes (3.54×10-3) exceeded the permissible threshold. Moreover, the waterpipe cafes that utilized fruit-flavored tobacco had the greatest CR (4.98×10-3). Furthermore, the presence of smoking, regional factors, and seasonal variations did not result in an increase in the hazard quotient (HQ) in houses beyond the acceptable thresholds. Finally, smoking, seasonal variations, and region had critical impact on indoor BTEX concentrations, and they could increase the risk of carcinogenic potential in the indoor environments.

Prediction of metachronous advanced colorectal neoplasia by KRAS mutation in polyps.

The potential of molecular markers in the removed polys as reliable predictors of metachronous lesions is still uncertain. Our aim was to evaluate the role of somatic mutations in KRAS in polyps of patients with high-risk adenomas to predict the risk of advanced polyps or colorectal cancer (CRC) within 3 years. A total of 518 patients were prospectively enrolled. The included patients had adenomas ≥10mm, high-grade dysplasia, villous component or ≥3 more adenomas at baseline and were scheduled to undergo surveillance colonoscopy at 3years±6months. Somatic KRAS mutation was performed on 1189 polyps collected from these patients. At surveillance, advanced lesions were defined as adenomas with a size of ≥10mm. High-grade dysplasia or villous component, serrated polyps ≥10mm or with dysplasia or CRC. At baseline, 81 patients (15.6%) had KRAS mutations in at least one polyp. Patients with KRAS mutated polyps had more frequent villous histological lesions and size ≥20mm. In the multivariate analysis, adjusted for age and sex, only age (odds ratios [OR], 1.06; 95% confidence interval [CI], 1.02-1.09; p<0.001), ≥5 adenomas (OR, 3.92; 95% CI, 1.96-7.82), and KRAS mutation (OR, 2.54; 95% CI, 1.48-4.34; p<0.01) were independently associated with the development of advanced lesions at surveillance. Our results show that, in patients with high-risk adenomas, the presence of somatic mutations in KRAS is an independent risk factor for the development of advanced metachronous polyps.

Postoperative pathological findings and prognosis of early laryngeal and pharyngeal cancer treated with transoral surgery

ObjectiveTransoral surgery for early-stage pharyngeal and laryngeal cancer provides good local control and is less invasive than external incisions. Postoperative pathological findings are considered the most important indicators for determining postoperative treatment, but detailed criteria have not been established. In this study, we evaluated the impact of postoperative pathological findings on prognosis of patients undergoing transoral surgery. MethodsThis study included patients with oropharyngeal, hypopharyngeal, and supraglottic cancer who underwent transoral surgery at Gifu University Hospital from April 2016 to December 2023. Resection margins were pathologically evaluated with horizontal and vertical margins, and vascular invasion was evaluated in three categories: lymphatic invasion, venous invasion, and perineural invasion. The correlation between each postoperative pathological finding and prognosis was evaluated. ResultsA total of 70 cases were assessed in this study. Cases of horizontal margin positive were 38.6 %, and cases of vertical margin positive were 27.1 %. Prognoses were comparable to previous reports. Despite the high margin positive rate, the 5-year overall survival rate was 77.1 %. The 5-year disease-specific survival rate was 89.7 %, and the 5-year local control rate was 85.3 %. Notably, when evaluated by margin direction, cases with positive horizontal margins had significantly worse prognoses. Although no significant correlation was found between vascular invasion and prognosis, cases of venous invasion tended to have a higher local recurrence rate. ConclusionThis study suggests that transoral surgery has good prognosis despite a high positive-margin rate. However, detailed criteria for additional treatment have not been developed, and further case accumulation is required. Intriguingly, positive horizontal margins are correlated with significantly worse prognosis. This result may be related to a high risk of multiple cancers, and careful follow-up after surgery is recommended.

Modern approaches to the eradication of &lt;i&gt;Helicobacter pylori&lt;/i&gt;: a spectrum of perspectives

Helicobacter pylori is one of the most widespread infections, affecting approximately 50% of the global population, with the Russian Federation ranking among the regions with a relatively high prevalence. Eradication therapy remains the primary strategy, not only for the treatment and prevention of gastrointestinal diseases but also for reducing the risk of stomach cancer, highlighting the medical and social impact of this infection. A key factor contributing to the reduced effectiveness of eradication therapy is the microorganism’s primary or secondary resistance to antibacterial drugs, a problem recognized worldwide. It is widely acknowledged that national treatment regimens for Helicobacter pylori infection must be adapted based on systematic antimicrobial sensitivity testing to curb the rise of global antibiotic resistance. Despite decades of research and clinical practice, identifying the most effective, safe, and straightforward therapy remains a significant challenge for clinicians. This review provides a comparative analysis of current treatment recommendations for Helicobacter pylori infection, as presented by various national and regional gastroenterological societies, including those relevant in the Russian Federation.

Association of erythrocyte fatty acid compositions with the risk of pancreatic cancer: A case-control study.

Pancreatic cancer (PC) is one of the most fatal malignancies, which has attracted scientists to investigate its etiology and pathogenesis. Nevertheless, the association between erythrocyte fatty acids and PC risk remains unclear. This study aimed to evaluate the association between levels of erythrocyte fatty acids and PC risk. The erythrocyte fatty acid compositions of 105 PC patients and 120 controls were determined by gas chromatography. Cases and controls were frequency matched by age and sex. Multivariable conditional logistic regression model and restricted cubic spline were applied to estimate the odds ratio with 95% confidence interval (OR, 95% CI) of erythrocyte fatty acids and PC risk. Our main findings indicated a significant negative association between levels of erythrocyte total monounsaturated fatty acids (MUFA) and n-3 polyunsaturated fatty acids (n-3 PUFA) and the risk of PC (ORT3-T1 = 0.30 [0.14, 0.63] and ORT3-T1 = 0.15 [0.06, 0.33], respectively). In contrast, erythrocyte n-6 polyunsaturated fatty acids, specifically linoleic acid (LA) and arachidonic acid (AA) levels, were positively associated with PC incidence (RT1-T3 = 4.24 [1.97, 9.46] and ORT1-T3 = 4.53 [2.09, 10.20]). Total saturated fatty acid (SFA), especially high levels of palmitic acid (16:0), was positively associated with the risk of PC (ORT3-T1 = 3.25 [1.53, 7.08]). Our findings suggest that levels of different types of fatty acids in erythrocytes may significantly alter PC susceptibility. Protective factors against PC include unsaturated fatty acids such as n-3 PUFA and MUFA.

Current exposure to environmental pollutants in the general adult population of Kinshasa, Democratic Republic of Congo (DRC): A cross-sectional study

BackgroundEnvironmental pollution is a serious public health problem because of its adverse effects on both human health and biodiversity. In Western countries, many human biomonitoring (HBM) studies are conducted to assess population exposure to pollutants. In contrast, the number of HBM studies in Africa is very low. ObjectiveTo measure contamination by arsenic, lead, 4,4′-dichlorodiphenyldichloroethylene (4,4′-DDE) and polychlorobiphenyls (PCBs) in the adult population of Kinshasa and to identify the susceptible population. MethodsIn the present work, we measured the contamination by arsenic in urine and lead in blood and by 4,4′-DDE and polychlorobiphenyls (PCBs) in serum in samples collected from 151 volunteers recruited in Kinshasa, the capital of the Democratic Republic of Congo (DRC). ResultsThe PCBs 180, -153 and −138 were detected in most samples with median concentrations of 0.04, 0.05 and 0.04 ng/ml, respectively. The median concentration of 4,4′-DDE was 0.83 ng/ml and 12.7% of our population showed contamination above the threshold of 3.675 ng/ml, which is associated with a significantly higher risk of cancer. Arsenic concentrations were also high (median: 48.1 μg/L in urine). Finally, exposure to lead is problematic: the median blood concentration was 54.9 μg/L, which is above the thresholds proposed by the WHO and the US CDC (50 μg/L and 35 μg/L respectively) to initiate clinical intervention, and 12.6% of the population had a lead level above 100 μg/L, which is associated with several health outcomes. ConclusionsOur results highlight the need for further HBM studies in Africa and should encourage the authorities of the DRC to implement laws and regulations to reduce pollution and population exposure.

Arsenic content in tissues, Fungus combs, Herbs, Termite mounds and Soils of termites of the genus Macrotermes and assessment of the health risk associated with their food use in the industrial zone of the Societe Nouvelle Des phosphates du Togo (SNPT)

Arsenic is present in different environmental matrices of the phosphate mining and processing area of the Société Nouvelle des Phosphates du Togo; including termite tissues, termite waste, termite mounds, termite Fungus combs, soils and nearby herbs. Arsenic levels vary across matrices, with termite waste having the highest concentration (approximately 27.01 mg/kg) compared to the outside herbs, which have the lowest. Phosphate mining sites, including Hahotoé-Kpogamé and Akoumapé, have higher levels of As contamination in soils and termite tissues compared to the phosphate processing site. A positive correlation is observed between As levels in termite tissues and termite waste; suggesting an ability of termites to eliminate arsenic via their waste. Regarding health risks, the hazard quotient (HQ) for arsenic in termites exceeds 1, and for non-threshold effects, the excess individual risk (EIR) assessment gives EIR &gt; 10-4 in both adults and children; which would mean that termite consumption poses a significant health risk, including cancer risks for human populations, particularly children. However, it should be noted that the estimation in this study includes total As (organic and inorganic). Since the toxicological reference values were calculated on the basis of inorganic arsenic, which presents more hazard and whose fraction represents 10% of total As, the daily exposure dose values for adults and children represent 1.40.10-4 mg/kg/d and 1.02.10-4 mg/kg/d of inorganic arsenic, respectively. These doses will then become lower than the toxicological reference value (TRV) with the consequence of hazard quotient (HQ) lower than 1 and resulting in low risks of carcinogenic effects. It is therefore necessary to specifically determine the inorganic fraction to refine the risk assessment and to extend this study to other trace elements in the prospected area.

Prediabetes persistence or remission and subsequent risk of gallbladder cancer: A nationwide cohort study

Background & aimsHyperglycemia is associated with an increased risk of gallbladder cancer (GBC), potentially by inhibiting gallbladder motility and inducing prolonged cholestasis. Although intermediate hyperglycemia (or prediabetes) is highly reversible, evidence is lacking about whether prediabetes persistence or remission is associated with an altered GBC risk. MethodsThis nationwide cohort study included 6058,662 adults without diabetes or cancer who underwent national health examinations twice in 2-year intervals between 2009 (S1) and 2011 (S2) and were followed-up until 2018. Prediabetes was defined as a fasting plasma glucose level of 100–125 mg/dL. We categorized changes in prediabetes status into: stable normoglycemia, new-onset prediabetes, prediabetes remission, and persistent prediabetes groups. GBC risk was estimated using Cox proportional hazards models, after adjusting for potential confounders. ResultsDuring 38.6 million person-years (median 6.4 years) of follow-up, 1349 new GBC cases were identified. Among 1409,474 individuals with prediabetes at S1, 768,515 achieved prediabetes remission at S2, outnumbering the 640,959 individuals with persistent prediabetes. GBC incidence probability was consistently higher among individuals with persistent prediabetes than in individuals with stable normoglycemia or prediabetes remission (all log-rank P < 0.01). Compared with stable normoglycemia, persistent prediabetes was associated with increased GBC risk (adjusted hazard ratio [aHR], 95 % CI: 1.21, 1.04 to 1.41). The aHRs of GBC were 1.14 (95 % CI, 0.99 to 1.33) and 1.03 (95 % CI, 0.88 to 1.21) for new-onset prediabetes and prediabetes remission, respectively. ConclusionsIndividuals with persistent prediabetes had a significantly increased risk of GBC, whereas those with prediabetes remission had no increased risk. Achieving prediabetes remission has a significant potential to reduce the risk of GBC.

Sex hormones and risk of lung and colorectal cancers in women: a Mendelian randomization study

The roles of sex hormones such as estradiol, testosterone, and sex hormone-binding globulin (SHBG) in the etiology of lung and colorectal cancers in women, among the most common cancers after breast cancer, are unclear. This Mendelian randomization (MR) study evaluated such potential causal associations in women of European ancestry. We used summary statistics data from genome-wide association studies on sex hormones and from the Trøndelag Health Study (HUNT) and large consortia on cancers. There was suggestive evidence of 1-standard deviation increase in total testosterone levels being associated with a lower risk of lung non-adenocarcinoma (hazard ratio 0.60, 95% confidence interval 0.37–0.98) in the HUNT Study. However, this was not confirmed by using data from a larger consortium. In general, we did not find convincing evidence to support a causal role of sex hormones on risk of lung and colorectal cancers in women of European ancestry.

Gastric Cancer in One-Anastomosis Mini-gastric Bypass: Case Report and Systematic Review.

In the last years, one-anastomosis gastric bypass (OAGB) has been proposed more frequently as obesity surgery technique. Several trials have demonstrated that the easier technical feasibility does not affect the long-term surgical result. However, concern about increased risk of gastric and esophageal cancers has been expressed by several bariatric surgeons. The present study reports the 2nd case of cancer of the gastrointestinal-jejunal anastomosis in a OAGB patient focusing the attention on some technical issues correlated and offering a systematic review of the literature.

Understanding the risk of ionizing radiation in breast imaging: Concepts and quantities, clinical importance, and future directions

BackgroundConventional mammography remains the primary imaging modality for state-of-the-art breast imaging practice and its benefit (both on diagnostic and screening) was largely reported. In mammography, the typical Mean Glandular Dose (MGD) from X-ray radiation to the breast spans, on average, from 1 to 10 mGy, depending on breast thicknesses, percentage of fibroglandular tissue, and on the examination purpose. MethodsThe aim of this narrative review is to describe the extent of radiation risk in X-ray breast imaging and discuss the main steps and parameters (e.g. MGD, screening frequency and number of examination views) that may have an influence on the radiation risk assessment. ResultsEven though the radiation doses used with these examinations are very low, as compared to other medical or natural radiation exposures, there is a non-negligible associated risk of radiation-induced cancer. Accurate radiation risk assessment permits to better balance the overall estimation of the benefit-to-risk ratio in X-ray breast imaging. ConclusionsIt is expected that a better knowledge about radiation-induced cancer risk among population could improve the communications skills between patients and clinicians and could help to increase the awareness in women about radiation risk perception for a transparent and proper informed choice of imaging exam.

Assessment of radiological contamination due to gold mining in soil and food crops of Babban Tsauni, Gwagwalada, Nigeria.

This work assessed the activity concentrations of 238U(226Ra), 232Th, and 40K and their associated radiological risks due to exposure to soil and consumption of food crops in Babban Tsauni artisanal gold mine, Gwagwalada, Nigeria, using the gamma spectrometry technique. The mean activity concentrations of 226Ra, 232Th, and 40K in the mine soil were 60.2±9.9, 161.4±16.2, and 664.6±138.2, while they were 46.4±4.9, 79.9±39.3, 266.4±185.4 for tubers and 46.9±15.7, 100.5±35.8, 311.4±132.7 (Bq/kg) for grains, respectively. The results reveal that the activity concentrations of radionuclides in all samples exceeded the recommended values set by United Nations Scientific Committee on the Effects of Atomic Radiation (33, 45, and 420 Bq/kg) except 40K, which fell within the acceptable limit in all food crop sample types. Estimated results for radiological hazard parameters, radium equivalent, annual effective dose due to ingestion, and excess life cancer risk were within safe limits, while the annual effective dose due to external gamma radiation in soil and annual gonadal equivalent dose were significantly high in all investigated samples; these call for constant radiological monitoring.

Revealing disease subtypes and heterogeneity in common variable immunodeficiency through transcriptomic analysis

Common Variable Immunodeficiency (CVID) is a primary immunodeficiency characterized by reduced levels of specific immunoglobulins, resulting in frequent infections, autoimmune disorders, increased cancer risk, and diminished antibody production despite an adequate B cell count. With its clinical manifestations being highly variable, the classification of CVID, including the widely recognized Freiburg classification, is primarily based on clinical symptoms and genetic variations. Our study aims to refine the classification of CVID by analyzing transcriptomics data to identify distinct disease subtypes. We utilized the GSE51405 dataset, examining transcriptomic profiles from 30 CVID patients without complications. Employing a combination of clustering techniques—KMeans, hierarchical agglomerative clustering, spectral clustering, and Gaussian Mixture models—and differential gene expression analysis with R’s limma package, we integrated molecular findings with demographic data (age and gender) through correlation analysis and identified common genes among clusters. Three distinct clusters of CVID patients were identified using KMeans, Agglomerative Clustering, and Gaussian Mixture Models, highlighting the disease’s heterogeneity. Differential expression analysis unveiled 31 genes with variable expression levels across these clusters. Notably, nine genes (EIF5A, RPL21, ANP32A, DTX3L, NCF2, CDC42EP3, CHP1, FOLR3, and DEFA4) exhibited consistent differential expression across all clusters, independent of demographic factors. The study recommends categorizing patients based on the four genes, NCF2, CHP1, FOLR3, and DEFA4—as they may assist in prognostic prediction. Transcriptomic analysis of common variable immunodeficiency (CVID) patients identified three distinct clusters based on gene expression, independent of age and gender. Nine differentially expressed genes were identified across these clusters, suggesting potential biomarkers for CVID subtype classification. These findings highlight the genetic heterogeneity of CVID and provide novel insights into disease classification and potential personalized treatment approaches.

To Drink or Not to Drink? Investigating Alcohol’s Impact on Prostate Cancer Risk

Background/Objectives: Prostate cancer (PCa) is a significant global health issue. The relationship between alcohol consumption and PCa risk has been the subject of extensive research, yet findings remain inconsistent. This review aims to clarify the association between alcohol intake and PCa risk, its aggressiveness, and the potential metabolic pathways involved in PCa onset. Methods: A comprehensive literature search was conducted across multiple databases, including PubMed and MEDLINE, focusing on epidemiological studies, meta-analyses, cohort studies, and case–control studies. Studies evaluating alcohol consumption, prostate-specific antigen (PSA) levels, and PCa risk were included. The review also explored the roles of alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH) in alcohol metabolism. Results: The analysis reveals a complex relationship between alcohol consumption and PCa. Heavy alcohol intake is associated with an increased risk of PCa, particularly more aggressive forms, and higher mortality rates. However, studies also show weak or no association between moderate alcohol consumption and PCa. The variability in findings may be attributed to differences in alcohol types, regional factors, and study methodologies. Conclusions: The link between alcohol consumption and PCa risk is multifaceted. While heavy drinking appears to increase the risk of aggressive PCa, the overall relationship remains unclear. Further research is needed to better understand these associations and inform public health recommendations and cancer prevention strategies.

Personal history of irradiation and risk of breast cancer: A Mendelian randomisation study.

Studies on the relationship between personal history of irradiation and breast cancer have been reported for a long time. Still, epidemiological studies have not been conclusive, and the causal relationship is unclear. To address this issue, we employed Mendelian randomisation (MR) analysis to examine the association between individual radiation exposure history and breast cancer. We used a series of quality control methods to select single nucleotide polymorphism (SNP) closely related to exposure. Meanwhile, several analysis methods were used to analyse the sample data to make the conclusion more reliable. To evaluate the horizontal pleiotropy, heterogeneity and stability of SNPs for breast cancer, the MR-Egger intercept test, Cochran's Q test and 'leave one' sensitivity analysis were used. Finally, the outlier variation determined by the Mendelian Randomisation Pleiotropy RESidual Sum and Outlier test is gradually eliminated to reduce the influence of heterogeneity and horizontal pleiotropy. After implementing rigorous quality control procedures, we carefully chose 102 qualified instrumental variables closely associated with the selected exposure for sensitivity analysis. This was conducted to evaluate the heterogeneity, level multiplicity, and stability of SNPs in the context of personal radiation history and its correlation with breast cancer. The results of the inverse variance weighted method analysis revealed a positive correlation between personal radiation and a heightened risk of breast cancer (odds ratio (OR) = 1.52; 95% confidence interval (CI) = 1.30-1.77). We also validated on another data set; the results were similar (OR = 1.51; 95% CI = 1.27-1.81). Furthermore, the findings from the sensitivity analysis were consistent. At the genetic level, our research demonstrated that personal radiation exposure is associated with an elevated risk of breast cancer. Using genetic data provides evidence and strengthens the causal link that personal radiation causes breast cancer.

Adverse pregnancy outcomes and multiple cancers risk in both mother and offspring: an umbrella review of systematic reviews with meta-analyses of observational studies

BackgroundAdverse pregnancy outcomes have reached epidemic proportions in recent years with serious health ramifications, especially for diverse cancers risk. Therefore, we carried out an umbrella review to systematically evaluate the validity and strength of the data and the extent of potential biases of the established association between adverse pregnancy outcomes and cancers risk in both mother and offspring.MethodsPubMed, Embase, and Web of Science databases were searched from inception until 18 January 2024. Meta-analyses of observational studies investigating the relationship between adverse pregnancy outcomes and multiple cancers risk in both mother and offspring were included. Evidence certainty was assessed using Grading of Recommendations, Assessment, Development, and Evaluation. The protocol for this umbrella review was prospectively registered in PROSPERO (CRD42023470544).ResultsThe search identified 129 meta-analyses of observational studies and 42 types of cancer. Moderate certainty of evidence, exhibiting statistical significance, has been observed linking per kilogram increase in birth weight to a heightened risk of breast cancer (OR = 1.07, 95% CI = 1.02–1.12), prostate cancer (OR = 1.02, 95% CI = 1.00–1.05), leukemia (OR = 1.18, 95% CI = 1.13–1.23), and acute lymphoblastic leukemia in offspring (OR = 1.18, 95% CI = 1.12–1.23); rubella infection during pregnancy to an increased risk of leukemia in offspring (OR = 2.79, 95% CI = 1.16–6.71); and a linear dose–response association between an increase in the proportion of optimal birth weight and an elevated risk of acute lymphoblastic leukemia in offspring (OR = 1.16, 95% CI = 1.09–1.24), respectively.ConclusionsAlthough some adverse pregnancy outcomes have clinically promising associations with risk of several cancers in both mother and offspring, it is essential to conduct additional research to solidify the evidence, evaluate causality, and ascertain clinical utility.

Extensive longevity and DNA virus-driven adaptation in nearctic Myotis bats.

The rich species diversity of bats encompasses extraordinary adaptations, including extreme longevity and tolerance to infectious disease. While traditional approaches using genetic screens in model organisms have uncovered some fundamental processes underlying these traits, model organisms do not possess the variation required to understand the evolution of traits with complex genetic architectures. In contrast, the advent of genomics at tree-of-life scales enables us to study the genetic interactions underlying these processes by leveraging millions of years of evolutionary trial-and-error. Here, we use the rich species diversity of the genus Myotis - one of the longest-living clades of mammals - to study the evolution of longevity-associated traits and infectious disease using functional evolutionary genomics. We generated reference genome assemblies and cell lines for 8 closely-related (∼11 MYA) species of Myotis rich in phenotypic and life history diversity. Using genome-wide screens of positive selection, analysis of structural variation and copy number variation, and functional experiments in primary cell lines, we identify new patterns of adaptation in longevity, cancer resistance, and viral interactions both within Myotis and across bats. We find that the rapid evolution of lifespan in Myotis has some of the most significant variations in cancer risk across mammals, and demonstrate a unique DNA damage response in the long-lived M. lucifugus using primary cell culture models. Furthermore, we find evidence of abundant adaptation in response to DNA viruses, but not RNA viruses, in Myotis and other bats. This is in contrast to these patterns of adaptation in humans, which might contribute to the importance of bats as a reservoir of zoonotic viruses. Together, our results demonstrate the utility of leveraging natural variation to understand the genomics of traits with implications for human health and suggest important pleiotropic relationships between infectious disease tolerance and cancer resistance.