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PURPOSE: To examine the association of a traditional Mexican diet score with risk of total, breast, and colorectal cancer among women of Mexican ethnic descent in the Womens Health Initiative (WHI). METHODS: Participants were WHI enrollees who self-identified as being of Mexican descent. Data from food frequency questionnaires self-administered at study baseline were used to calculate the MexD score, with higher scores indicating greater adherence to an a priori-defined traditional Mexican diet (high in dietary fiber, vegetables, and legumes). Incident cancers were self-reported by participants from 1993 to 2020 and adjudicated by trained physicians. We used multivariable-adjusted Cox proportional hazards models to calculate hazard ratios (HRs) and 95% confidence intervals (CIs). RESULTS: Among 2,343 Mexican descent women (median baseline age: 59 years), a total of 270 cancers (88 breast, 37 colorectal) occurred during a mean follow-up of 14.4 years. The highest tertile of MexD score was associated with a lower risk of all-cancer incidence (HR: 0.67; 95% CI 0.49-0.91; p-trend: 0.01) and colorectal cancer (HR: 0.38; 95% CI 0.14-0.998; p-trend

This study aimed to understand long-term coping responses of mothers (N = 287) receiving genetic counseling and testing (GCT) for hereditary breast/ovarian cancer (HBOC) syndrome. Psychological characteristics, including cancer-specific distress (Impact of Events Scale-Revised, α = .85) and coping (Brief COPE, α = .93) were assessed via structured personal communication, along with epidemiologic items assessing personal and family history of cancer. Genetic risk was determined by BRCA1/2 carriage. A principal component analysis was conducted on the coping measure to reduce its summary score to active coping (α = .91) with nine approach-oriented strategies responsive to stress. A multivariable regression model examined the main and interacting effects of clinical and psychological characteristics on maternal coping. Personal cancer history (F = 4.99, df = 1, p = .026), BRCA test result (F = 22.20, df = 1, p < .001), and cancer-specific distress (F = 17.80, df = 1, p < .001) were associated with greater engagement in active coping strategies. When controlling for cancer-specific distress, the interaction between personal cancer history and genetic test results was significant, such that women previously unaffected by cancer who received positive BRCA results reported the greatest levels of active coping (F = 7.92, p < .001). These findings indicate that previous cancer history, genetic risk, and psychological distress independently and jointly impact how women adapt to the threat of cancer over time. [ABSTRACT FROM AUTHOR]

AbstractPurposeConclusionIn this short tale, we describe a year of Pierre Chris Curry’s ionizing radiation (IR) exposure, assessing and summarizing how much he has been exposed to over a year of his fictive life, cumulating the different types of exposures (either due to natural radiation, occupational and medical exposure), while staying reasonably credible. We have limited ourselves to IR exposure. As a recognized specialist in interventional cardiac surgery, Pierre provides lectures at international conferences requiring overseas flights. When not traveling, Pierre lives in Brittany in an area where there is high natural background radiation, owing to significant concentrations of radon, a radioactive gas produced from the natural radioactive decay of uranium found in rocks, granite in this case.Natural exposures correspond to half of Pierre’s total yearly exposure. Therefore, where you live, and your life habits have an important impact on your radiation exposure levels. Medical exposures take the second place in the ranking, but these exposures are punctual. Although his professional exposure is the lowest percentage, this represents a chronic exposure which is continuous over the duration of his working life, and alongside the natural exposure, is building on over-time. Although Pierre calculated total yearly dose was 58.4 mSv, significantly higher than the average in countries such as France, UK or even USA, his excess risk of death from cancer was still very low 0.292%. [ABSTRACT FROM AUTHOR]

Over the years, prostate cancer (PCa) research has been of great interest, and trace metals have attracted a lot of attention due to their association with prostate cancer development and progression. PCa has a complex etiology, with genetic, environmental, and lifestyle factors being implicated. Trace metals such as zinc (Zn), mercury (Hg), selenium (Se), lead (Pb), cadmium (Cd), manganese (Mn), arsenic (As), and nickel (Ni) have garnered much attention in recent years, suspected of having direct links to the modulation of cancer risk and progression through their impacts on prostate cancer omics (genomics, epigenetics, proteomics, and transcriptomics). This has led to them being the subject of extensive research in this regard. In this review, we explored the influence of trace metals and offered a comprehensive analysis of the current knowledge on how trace metals affect the biology of prostate cancer at a molecular level by integrating findings from the recent literature to help suggest possible directions for future research. [ABSTRACT FROM AUTHOR]

Single nucleotide polymorphisms (SNPs) of the IL-16 gene have been reported to influence the risk of several cancers, but their role in ovarian cancer (OC) has not been studied. Using the restriction fragment length polymorphism (PCR-RFLP) method, we examined four IL-16 SNPs: rs11556218 (T > G), rs4778889 (T > C), rs4072111 (C > T), and rs1131445 (T > C) in blood samples from 413 women of Central European descent, including 200 OC patients and 213 healthy controls. Among the patients, 62% were postmenopausal, 84.5% were diagnosed in late stages (FIGO IIb-IV), and 73.5% had high-grade serous OC (HGSOC). Minor allele frequencies in controls were 9.2% for rs11556218 (G allele), 13.7% for rs4778889 (C allele), 10.4% for rs4072111 (T allele), and 32.3% for rs1131445 (C allele). We found significant associations of rs11556218 (G vs. T allele: OR 2.76, 95% CI 1.84–4.14, p < 0.0001) with elevated OC risk in the whole cohort (p < 0.001) and in both premenopausal (p < 0.001) and postmenopausal (p = 0.001) subgroups. These associations remained significant across heterozygote (p < 0.001), dominant (p < 0.001), and overdominant (p < 0.001) models. IL-16 rs4778889 was associated with OC risk predominantly in premenopausal women (p < 0.0001 in almost all models). In the whole cohort, the C allele was associated with OC risk (OR 1.54, CI 95% 1.06–2.23, p = 0.024), and the association of rs4778889 was significant in dominant (p = 0.019), overdominant (p = 0.033), and heterozygote (p = 0.027) models. Furthermore, rs4778889 was linked with HGSOC (p = 0.036) and endometriosis-related OC subtypes (p = 0.002). No significant associations were found for rs4072111 or rs1131445 (p = 0.81 or 0.47, respectively). In conclusion, rs11556218 and rs4778889 SNPs are associated with OC risk, especially in premenopausal women. [ABSTRACT FROM AUTHOR]

Background: Population-based studies that examine the associations between hyperthyroidism and cancer risk have yielded inconsistent results. It remains unclear whether the risks of different cancers increase in patients with Graves' disease (GD) who received antithyroid drugs (ATDs) as initial treatment. We aimed to determine whether cancer risk increases in patients with GD, compared with controls. Methods: This nationwide retrospective cohort study utilized data from the National Health Information Database of South Korea. We included 29,502 patients aged >20 years with GD, who received ATDs as initial treatment, and 57,173 age- and sex-matched controls. The primary outcome was the incidence of various types of cancers. Hazard ratios (HRs) with confidence intervals (CIs) for cancer risk were estimated using Cox proportional hazards models. We also analyzed HR by follow-up period since the diagnosis of GD, accounting for surveillance effect. Results: The risk of biliary tract and pancreatic cancers (HR: 1.41, CI: 1.24–1.60), thyroid cancer (HR: 15.51, CI: 12.29–19.57), prostate cancer (HR: 1.48, CI: 1.28–1.71), and ovarian cancer (HR: 1.31, CI: 1.13–1.52) was elevated in the GD group than in the control group even after the first year of follow-up was excluded. The increased risk of these cancers persisted after a follow-up period of more than 5 years. The risk of thyroid cancer in patients with GD was higher during the initial follow-up period (1 to <2 years) (HR: 19.35, CI: 7.66–48.87) compared with that in the follow-up period exceeding 2 years. The cancer risk estimates remained significant after excluding patients with GD who underwent subsequent radioactive iodine therapy. Conclusion: In this large-scale population-based study, GD was associated with increased risks of biliary tract and pancreatic, prostate, ovarian, and thyroid cancers. The increased risk of thyroid cancer, particularly during the initial follow-up period, may be a surveillance effect. [ABSTRACT FROM AUTHOR]

Background Aluminium industry workers are at risk of long-term health consequences. Aims To investigate mortality and cancer incidence in bauxite mine and alumina refinery workers. Methods A pre-existing cohort of workers was re-linked with the Australian National Death Index, and the Australian Cancer Database to provide additional death (7 years) and cancer (9 years) data. Standardized mortality ratios (SMRs) and standardized incidence rates (SIRs) were estimated by job category, duration of employment and time since first employment. Results Linkage was performed for 6935 (6207 male) workers. Compared with the general population, there was a reduced or similar risk of death for mine/refinery workers for all causes except mesothelioma which was increased amongst male production workers [SMR 2.42, 95% CI 1.11–4.60]. Mesothelioma incidence was also increased amongst males [SIR 2.50, 95% CI 1.60–3.71]. Male office workers had a greater incidence of prostate cancer [SIR 1.30, 95% CI 1.06–1.57] and thyroid cancer [SIR 3.47, 95% CI 1.66–6.38]. Melanoma incidence was increased in female office workers [SIR 2.27, 95% CI 1.36–3.54]. Lip cancer incidence was increased in male maintenance/production workers [SIR 2.04, 95% CI 1.02–3.65]. Overall cancer incidence was otherwise similar to the general Australian population. Conclusions Overall risk of death and incidence of cancer for bauxite mine and alumina refinery workers was similar to the general population. Incidence and risk of death from mesothelioma were higher, likely due to historic asbestos exposure in this and other industries. The increased risk of melanoma, lip, prostate and thyroid cancers requires further investigation. [ABSTRACT FROM AUTHOR]

Radiation has been acknowledged to be responsible for deleterious conditions in living tissues. Hence, environmental background gamma radiation (BGR) measurement is crucial from an environmental and health perspective. In this study, due to the absence of comprehensive background gamma radiation data and the increasing numbers of anthropogenic activities that could increase the BGR level, such as where mining activities are active. The BGR in the Minna area of Niger State, Nigeria, was measured and analyzed in this study. In-situ measurement of the background gamma radiation level was carried out using a well-calibrated portable handheld GQ GMC-500 Plus nuclear radiation detector at an elevation of about 1.0 m above ground level. A global positioning system from Garmin (GPSmap 78s) was adopted for identifying geographical locations. A total of 1172 points were surveyed across the study area for background environmental radiation. The BGR values ranged from 0.102 to 0.147 μSv/h, with an overall mean value of 0.126 μSv/h. The average measured dose rate was more than twice the reported world average value of 0.059 μSv/h. The annual effective dose equivalent (AEDE) for the research area was calculated to be 0.221 mSv/y on average. The mean AEDE is lower than the ICRP recommended limit. This shows that the population of the Minna area is radiologically safe based on the estimated AEDE value. Similarly, the excess lifetime cancer risk (ELCR) value ranged from 0.626 × 10−3 to 0.901 × 10−3 mSv/y with a mean value of 0.774 ± 0.09 × 10−3 mSv/y. The mean value of AEDE is below the 0.24 mSv/y permissible limits as recommended by the International Commission on Radiological Protection (ICRP). The mean ELCR value exceeds the average world value of 0.29 × 10−3. Also, the mean organ dose values estimated for the whole body, liver, kidney, testes, bone marrow, ovaries, and lungs are 0.150 ± 0.02, 0.102 ± 0.01, 0.137 ± 0.02, 0.181 ± 0.02, 0.152 ± 0.02, 0.128 ± 0.02 and 0.141 ± 0.02 mSv/y respectively. The differences in the calculated mean of BGR were attributed to natural and human factors. Geological variation is a fundamental factor that influences the changes in BGR. Human activities, mining, building materials, and the use of phosphate fertilizers in agricultural practices are responsible for the differences in BGR. The ELCR implies that terrestrial gamma radiation does not pose any immediate radiological health effects on residents of the area, but there is a tendency for long-term health hazards in the future, such as cancer, due to the dose accumulated. [ABSTRACT FROM AUTHOR]

Living beings get inevitable exposure to radiation of which approximately half of the dose is due to natural background radiation. In the present study, an extensive and systematic survey of outdoor GDR (GDR) was carried out in Churu and Jhunjhunu districts of Rajasthan. A total of 687 locations were covered to quantify the outdoor GDR. The portable radiation monitor, based on the Geiger-Muller counter, was used to monitor the outdoor gamma dose, and its associated health risk was estimated. Outdoor GDRs were found to vary from 32 nSv/h to 231 nSv/h and 75 nSv/h to 188 nSv/h in Churu and Jhunjhunu districts, respectively. The annual effective dose at most locations of the study area was greater than 0.07 nSv/h but less than the 1 mSv/y permissible limit recommended by the ICRP. The excess lifetime cancer risk in Churu district was estimated and found to range from 0.147 × 10−3 to 1.063 × 10−3, while in Jhunjhunu district it was 0.345 × 10−3 to 0.865 × 10−3 [ABSTRACT FROM AUTHOR]

In this study, the activity concentration of artificial and natural radionuclides such as 137Cs, 40K, 226Ra, and 232Th was measured in the soil under the roots; leaves; and fruits of six different fruit trees namely mulberry, fig, apricot, olive, black and white grapes in Koya district, Erbil province, Iraq. For this purpose, a high-resolution gamma spectroscopy consisting of a high-purity germanium (HPGe) detector was used. In addition, the associated radiological risks from soil and fruits were assessed by calculating several radiological indices such as radium equivalent (Raeq.s), absorbed dose (Ds), indoor (AEDEsindoor) and outdoor annual effective doses (AEDEsoutdoor), internal and external hazard indices, gamma index and the excess lifetime cancer risk (ELRCs). The results show that consuming these fruits is radiologically safe because they can cause an annual effective dose of about 61.72 μSv y−1 and excess lifetime cancer risk of 0.06 × 10−3 Sv y−1. On the other hand, transfer factors of radionuclides from soil to leaves; and from soil to fruits were studied. The transfer factor analysis revealed that among the studied fruits and radionuclides, apricot and mulberry exhibited the highest transfer factors for 40K, with values of 1.85 and 1.87, respectively. [ABSTRACT FROM AUTHOR]

Background: In Norway, we have offered testing of PMS2 since 2006, and have a large national cohort of carriers. The aim of this study was to describe all PMS2 variants identified, and to describe frequency, spectrum and penetrance of cancers in carriers of class 4/5 variants. Methods: All detected PMS2 variants were collected from the diagnostic laboratories and reclassified according to ACMG criteria and gene specific guidelines. Data on variant, gender, cancer diagnosis, age at diagnosis, and age at last known follow-up was collected on all carriers of class 4/5 variants from electronic patient records. The Kaplan-Meier algorithm was used to calculate cumulative risk of any cancer, colorectal cancer and endometrial cancer. Results: In total, 220 different PMS2 variants were detected. Twenty nine class 4/5 variants were identified in 482 carriers. The most common pathogenic variant was the founder mutation c.989-1G > T, detected in 204 patients from 58 families. Eighty seven out of 482 (18.0%) had been diagnosed with colorectal cancer, 10 of these (11.8%) before 40 years. Cumulative risk at 70 years in our cohort was 34.7% for colorectal cancer and 26.1% for endometrial cancer. Conclusions: After 15 years of genetic testing, 29 different class 4/5 variants have been detected in Norway. Almost half of Norwegian PMS2 carriers have the founder variant 989-1G > T. Penetrance of colorectal cancer in our cohort was moderate but variable, as 11.5% of those diagnosed were younger than 40 years. [ABSTRACT FROM AUTHOR]

Since the onset of the COVID-19 pandemic, the SARS-CoV-2 virus has caused over 600million confirmed infections andmore than 6.8 million deathsworldwide, with ongoing implications for human health. COVID-19 has been extensively documented to have extrapulmonary manifestations due to the widespread expression of necessary ACE2 receptors in the human body. Nevertheless, the association between COVID-19 and cancer risk remains inadequately explored. This study employs Mendelian randomization (MR) methods to examine the causal relationship between genetic variations associated with COVID-19 and the risk of developing cancer. The findings indicate that COVID-19 has negligible impact on most cancer risks. Interestingly, a higher COVID-19 impact is associated with a decreased risk of thyroid cancer. In summary, our findings demonstrate a genetic correlation between COVID-19 and thyroid cancer, contributing to our understanding of the interplay between COVID-19 and cancer risk. [ABSTRACT FROM AUTHOR]

Objective: To investigate whether Molybdenum blood level is a marker of cancer risk on BRCA1 carriers. Methods: A prospective cohort study was conducted among 989 initially unaffected women with a BRCA1 mutation. Blood samples were collected to measure molybdenum levels, and participants were followed for an average of 7.5 years. Cox proportional hazards models were used to assess the association between blood molybdenum levels and cancer incidence, adjusting for potential confounders. Results: High blood molybdenum levels (> 0.70 µg/L) were significantly associated with an increased risk of developing ovarian cancer (HR = 5.55; 95%CI: 1.59–19.4; p = 0.007) and any cancer (HR = 1.74; 95%CI: 1.17–2.61; p = 0.007) but not breast cancer (HR = 1.46, CI = 0.91–2.33; p = 0.12). The cumulative incidence of ovarian cancer at ten years was 1.2% for the lowest molybdenum tertile, 4.2% for the middle tertile, and 8.7% for the highest tertile. Conclusion: Elevated blood molybdenum levels are associated with an increased risk of ovarian cancer on BRCA1 mutation carriers. Lowering molybdenum levels may potentially reduce cancer risk in this population, and high molybdenum levels could serve as a marker for considering preventive oophorectomy in BRCA1 carriers. Further research is warranted to confirm these findings and explore interventions targeting molybdenum levels as a preventive measure for ovarian cancer in BRCA1 mutation carriers. [ABSTRACT FROM AUTHOR]

This study presents a new risk assessment of pulegone, a substance classified as possibly carcinogenic to humans (Group 2B) by the WHO International Agency for Research on Cancer (IARC). The analysis used data from a two-year carcinogenicity studies in rats and mice conducted by the National Toxicology Program (NTP) in 2011. Because of the absence of a no-observed adverse effect level (NOAEL) in these studies, the benchmark dose (BMD) approach was employed as an alternative risk assessment method. The lowest BMD lower confidence level (BMDL) of 4.8 mg/kg b.w./day among the eight endpoints served as the point of departure for calculating an acceptable daily intake (ADI) of 48 μg/kg b.w./day. This new ADI is significantly lower than the previously established tolerable daily intake of 0.1 mg/kg b.w./day set in 1997. The analysis also considered various genotoxicity studies, which indicate that pulegone's effects follow a nongenotoxic, thresholded mechanism. The estimated intake levels of pulegone in the European Union and USA were below the newly calculated ADI, suggesting a low health risk based on current consumption patterns. [ABSTRACT FROM AUTHOR]

While selenium is a cofactor of several antioxidant enzymes against cancer and is essential for human health, its excess intake may also be harmful. Though a safe intake of selenium has recently been recommended, it is not well understood in the Asian population. We aimed to determine the association between dietary intake of selenium and cancer risk in a case–control study of 3758 incident cancer cases (i.e., stomach, colon, rectum, lung cancers, and other sites) and 2929 control subjects in Vietnam. Daily intake of selenium was derived from a semiquantitative food frequency questionnaire. The unconditional logistic regression model was used to calculate the odds ratios (ORs) and 95% confidence intervals (CIs) for the association between selenium intake and cancer risk. We observed a U-shaped association between selenium intake and cancer risk. A safe intake ranged from 110.8 to 124.4 µg/day (mean 117.8 µg/day). Compared to individuals with the safe intake of selenium, individuals with the lowest intake (i.e., 27.8–77.2 µg/day) were associated with an increased risk of cancer (OR = 3.78, 95% CI 2.89–4.95) and those with the highest intake (169.1–331.7 µg/day) also had an increased cancer risk (OR = 1.86, 95% CI 1.45–2.39). A U-shaped pattern of association between selenium intake and cancer risk was stronger among participants with body mass index (BMI) < 23 kg/m2 and never smokers than BMI ≥ 23 kg/m2 and ever smokers (P’sheterogeneity = 0.003 and 0.021, respectively) but found in both never and ever-drinkers of alcohol (Pheterogeneity = 0.001). A U-shaped association between selenium intake and cancer risk was seen in cancer sites of the stomach, colon, rectum, and lung cancers. In summary, we found a U-shaped association between selenium intake and cancer risk and a safe selenium intake (mean: 117.8 µg/day) in the Vietnamese population. Further mechanistic investigation is warranted to understand better a U-shaped association between selenium intake and cancer risk. [ABSTRACT FROM AUTHOR]

Utilizing molecular dynamics and free energy perturbation, we examine the relative binding affinity of several covalent polycyclic aromatic hydrocarbon - DNA (PAH-DNA) adducts at the central adenine of NRAS codon-61, a mutational hotspot implicated in cancer risk. Several PAHs classified by the International Agency for Research on Cancer as probable, possible, or unclassifiable as to carcinogenicity are found to have greater binding affinity than the known carcinogen, benzo[a]pyrene (B[a]P). van der Waals interactions between the intercalated PAH and neighboring nucleobases, and minimal disruption of the DNA duplex drive increases in binding affinity. PAH-DNA adducts may be repaired by global genomic nucleotide excision repair (GG-NER), hence we also compute relative free energies of complexation of PAH-DNA adducts with RAD4-RAD23 (the yeast ortholog of human XPC-RAD23) which constitutes the recognition step in GG-NER. PAH-DNA adducts exhibiting the greatest DNA binding affinity also exhibit the least RAD4-RAD23 complexation affinity and are thus predicted to resist the GG-NER machinery, contributing to their genotoxic potential. In particular, the fjord region PAHs dibenzo[a,l]pyrene, benzo[g]chrysene, and benzo[c]phenanthrene are found to have greater binding affinity while having weaker RAD4-RAD23 complexation affinity than their respective bay region analogs B[a]P, chrysene, and phenanthrene. We also find that the bay region PAHs dibenzo[a,j]anthracene, dibenzo[a,c]anthracene, and dibenzo[a,h]anthracene exhibit greater binding affinity and weaker RAD4-RAD23 complexation affinity than B[a]P. Thus, the study of PAH genotoxicity likely needs to be substantially broadened, with implications for public policy and the health sciences. This approach can be broadly applied to assess factors contributing to the genotoxicity of other unclassified compounds. [ABSTRACT FROM AUTHOR]

Germline pathogenic genetic variants in the BRCA1 and BRCA2 genes are the most frequent causes of familial breast and ovarian cancer. Contrasting BRCA2, epimutations in the BRCA1 gene are frequently detected in tissue from triple‐negative breast (TNBC) and high‐grade serous ovarian cancers (HGSOC). While studies over the last decade have reported BRCA1 epimutations in white blood cells (WBC) from breast and ovarian cancer patients, the potential hazard ratio for incident TNBC and HGSOC was not formally assessed until recently. Conducting a prospective nested case‐control study on women participating in the American Women's Health Initiative Study, we provided firm evidence that mosaic WBC BRCA1 epimutations, even at allele frequencies < 0.1%, are associated with a significantly increased risk of both incident HGSOC and TNBC > 5 years after WBC collection. In a second study assessing BRCA1 epimutations in WBC and matched tumor samples from TNBC, our results indicated such epimutations to be the underlying cause of around 20% of TNBC, far exceeding the percentage of cases carrying BRCA1 germline pathogenic genetic variants. We detected primary constitutional BRCA1 epimutations in tissues derived from all three germ layers. They occur independently of BRCA1 promoter haplotypes but are present on the same allele in all WBC within affected individuals. Moreover, epimutations are consistently found on the same allele in normal and tumor breast tissue as well as in WBC. This finding, together with BRCA1 epimutations detected in WBC from newborns, strongly indicates an early embryonic event with clonal expansion affecting all germ layers. Future work in the field must lead to an understanding of exactly when and how the BRCA1 epimutations occur and, most importantly, whether primary constitutional epimutations in genes other than BRCA1 may cause an elevated risk of other cancer types. [ABSTRACT FROM AUTHOR]

Immunotherapy has emerged as a pivotal modality in cancer treatment, with immune checkpoint inhibitors effectively combating malignancies by impeding crucial pathways within the immune system and stimulating patients' immune responses. Soluble forms of immune checkpoints exhibit a remarkable diversity and can be readily tracked in circulation, holding immense potential as biomarkers for cancer treatment. An increasing number of studies focused on soluble immune checkpoints in cancer have emerged thanks to technological advancements. In this systematic review, we comprehensively summarized the recent studies on soluble immune checkpoints in human cancer risk prediction, outcome prediction, therapeutic applications, and potential molecular mechanisms, which demonstrated the promising future of soluble immune checkpoints in clinical applications. The clinical relevance of soluble immune checkpoints has been recognized in multiple cancers, yet the therapeutic applications and mechanisms remain obscure. Interpreting the impacts and mechanisms of soluble immune checkpoints could shed a light on the novel strategies of cancer screening, treatments, and outcome prediction. [ABSTRACT FROM AUTHOR]

Pathological germline variants (PGVs) of RAD51D increase the risk of breast and ovarian cancer. In East Asia, c.270_271dup is the most frequently detected PGV of RAD51D; however, only a few cases have been reported in Japan. We report four cancer cases with a germline RAD51D c.270_271dup PGV. Three of them (lung cancer: 2, oral cancer: 1) were incidentally identified by whole genome sequencing in patients negative for the associated cancer histories, homologous recombination (HR) deficiency, or a second hit of RAD51D in the cancer DNA. For genetic counseling, we provided information on surveillance and cascade testing based on Western guidelines. The PGVs of moderate‐risk HR‐related genes are difficult to detect based on phenotype, especially in male‐predominant pedigrees. The current spread of cancer genomic analysis will increase opportunities for incidental variant identification. The establishment of Japanese guidelines is expected to aid in the management of PGV carriers of moderate‐risk genes. [ABSTRACT FROM AUTHOR]

Changes caused by air-cleaning devices in the amounts of volatile organic compounds in an intensive care unit were monitored in the study. The cancer risk and hazard index were calculated. The measurements were made for one month at isolated room and two different points and times in the intensive care unit. According to the sampling program, the air-cleaning devices were turned off in weeks 1 and 4 and turned on in weeks 2 and 3. Volatile organic compounds were collected by active sampling. Samples were analyzed by a thermal desorber coupled to a gas chromatography-mass spectrometry instrument with selective ion monitoring. The results showed that the concentrations of benzene, toluene, and o-xylene decreased by about 70% after the air-cleaning devices were installed. The cancer risk assessment for naphthalene was recorded at the highest level of cancer risk (Class A). The hazard index value of naphthalene was recorded at the harmful level when air-cleaning devices were not installed. The concentrations of benzene (p = 0.01), toluene (p = 0.02), ethylbenzene (p = 0.02), styrene (p = 0.01), and m, p-xylene (p = 0.04) before the air-cleaning devices were installed were significantly different from those recorded when the air-cleaning devices were turned on. [ABSTRACT FROM AUTHOR]

Background: Head and neck squamous cell carcinoma (HNSCC) is one of the most prevalent cancers worldwide. The identification of molecular alterations adding to the individual risk of HNSCC development and progression is one of the most important challenges in studies on cancer genetics. MicroRNAs (miRNAs), which belong to the group of important post-transcriptional regulators of human gene expression, seem to be valuable options for consideration as key modifiers of individual cancer risk, and therefore may be helpful in predicting inter-individual differences in cancer risk, response to treatment and prognosis. Methods: There have not been many studies focused on the relationship between miRNA variants and HNSCC published in PubMed within the last 15 years. We found and analyzed 30 reviews, meta-analyses and research papers and revealed 14 SNPs which have been reported as significant in the context of HNSCC susceptibility and/or prognosis. Results: These 14 SNPs were located in 13 separate miRNAs. Among them, four were the most frequently studied (miRNA-146, -196, -149 and -499) and have been shown to have the greatest impact on the course of HNSCC. However, the presented results have been conflicting. Conclusions: It must be concluded that, despite the years of studies, there are no conclusive reports demonstrating a significant role of SNPs in miRNAs in the context of the susceptibility to HNSCC or its prognosis. [ABSTRACT FROM AUTHOR]

Obesity is a big public health problem that claims several thousand lives every year. Bariatric surgery has arisen as a suitable procedure for treating obesity, particularly morbid obesity. Oxidative stress, genotoxicity, apoptosis, and inflammatory responses are recognized as the most important occurrences in carcinogenesis, as they actively contribute to the multistep process. This study aimed to briefly review the connection between oxidative stress, genotoxicity, apoptosis, and inflammation in obese patients undergoing bariatric surgery, focusing on its impact on carcinogenesis. Regarding oxidative stress, bariatric surgery may inhibit the synthesis of reactive oxygen species. Moreover, a significant reduction in the inflammatory status after weight loss surgery was not observed. Bariatric surgery prevents apoptosis in several tissues, but the maintenance of low body weight for long periods is mandatory for mitigating DNA damage. In conclusion, the association between bariatric surgery and cancer risk is still premature. However, further studies are yet needed to elucidate the real association between bariatric surgery and a reduced risk of cancer. [ABSTRACT FROM AUTHOR]

Previous studies showed an association between single nucleotide gene variants (SNVs) of PD-1 and cancer susceptibility. We analyzed PD1.5 C > T and PD1.7 T > C SNVs to investigate their association with the risk of developing metastatic melanoma (MM). Utilizing a cohort of 125 MM patients treated with anti-PD-1 agents and 84 healthy controls, we examined genotype/allele frequencies through a modified Poisson regression model, adjusted for age and sex. Our findings indicate that the PD1.5 T allele is associated with a reduced risk of MM, showing a significantly lower risk in both codominant (RR = 0.56, 95%CL: 0.37–0.87) and dominant (RR = 0.73 95%CL: 0.59–0.90) models. Conversely, the PD1.7 C allele is linked to an increased risk of MM, with the C/C genotype exhibiting a higher risk in the codominant (RR = 1.65, 95%CL: 1.32–2.05) and allelic (RR = 1.23, 95%CL: 1.06–1.43) models. These results are consistent with previous meta-analyses on other cancer types, mainly highlighting the PD1.5 SNV’s potential role in promoting anti-tumor immunity through increased PD1-positive circulating effector T cell activity. [ABSTRACT FROM AUTHOR]

The quality of non-alcoholic beverages consumed in Aba, Abia State, southeastern Nigeria and health risk assessment of heavy metals required periodic evaluation so as to avert potential health hazard. Hence, the objective of this paper as to evaluate the hazard and health risk assessment of heavy metals in non-alcoholic beverages consumed in Abia State, Nigeria using health risk assessment models. Heavy metals concentrations were determined using atomic absorption spectrophotometer (Agilent 280FS AA). The average heavy metal concentrations of non-alcoholic drink samples ranged from 0.040 - 1.132 mg/l in ascending order of Zn < Cd < Co < Cu < Pb 1.0), signifying potential chronic health risk as a result of combine effects of these heavy metals. The incremental life cancer for Cr, Cd and Pb ranged from 2.59E-05 - 1.79E-03, 1.35E-04 - 2.81E-04 and 3.92E-06 - 3.24E-05 respectively. The incremental life cancer values of Pb were within the recommended safe limit of not greater than 1.0 x 10-4 and has the least likelihood of any potential cancer risks. However, Cd, and Cr had cancer risk values higher than the save limits, indicating potential life cancer health risks in both children and adult population. [ABSTRACT FROM AUTHOR]

A 2018 report from the Water Quality for Human Consumption Vigilance Information System (SISÁGUA, Brazil) showed the presence of 27 pesticides in Brazilian drinking water, of which 11 have carcinogenic potential. We assessed the data for 27 municipalities in Paraná state southwest, a rural landscape with high cancer rates. We selected data from the carcinogenic potential of 11 pesticides provided by international agencies (alachlor, aldrin-diheldrin, atrazine, chlordane, DDT, diuron, glyphosate, lindane, mancozeb, molinate, and trifluralin) and estimated the number of cancer cases attributable to drinking water contamination by pesticides. Also, we correlated such findings with incidence and mortality cancer rates for ten topographies obtained from the Brazilian National Cancer Institute (INCA) database. A total of 9 cities were selected, corresponding to about 81,000 people. All towns had all pesticides quantified in the drinking water. About ten cancer cases were attributed to drinking water contamination by pesticides in 2014–2017, mainly linked to diuron and mancozeb. Concerning the consolidated incidence of cancer cases reported by the INCA, significant correlations were found regarding aldrin-diheldrin, alachlor, and atrazine for breast cancer, atrazine for prostate cancer, and mancozeb and diuron for colon cancer, among others. Regarding the consolidated mortality rates, some correlations were found between DDT and trifluralin for the breast, DDT and lindane for the prostate, and glyphosate for lung cancer. Moderate correlations were found between the estimated and consolidated cancer cases for several topographies. Our findings highlight the correlation between drinking water contamination in Paraná state southwest and its increased incidence of cancers with poor prognosis. [ABSTRACT FROM AUTHOR]

The association between periodontal diseases and the risk of gastrointestinal cancers, especially site-specific gastrointestinal cancers, remains unclear. Here, we comprehensively searched PubMed, EMBASE, Web of Science, and Google Scholar from inception to April 2024 to identify relevant studies. The pooled hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated with a random-effects model. Subgroup analyses and sensitivity analyses were conducted to confirm the robustness of the main findings in different populations. This study was reported according to PRISMA 2020 guidelines. In total, we identified 19 studies, including 16.6 million participants. Individuals with periodontal diseases had an increased risk of overall gastrointestinal cancers compared with those without periodontal diseases (HR 1.31, 95% CI 1.16–1.49). Periodontal diseases significantly increased the risk of esophageal cancer by 39% (HR 1.39, 95% CI 1.15–1.68), gastric cancer by 13% (HR 1.13, 95% CI 1.01–1.26), colorectal cancer by 21% (HR 1.21, 95% CI 1.05–1.39), pancreatic cancer by 35% (HR 1.35, 95% CI 1.00–1.82), and liver cancer by 9% (HR 1.09, 95% CI 1.04–1.13). The risk of gastrointestinal cancers was significantly increased by periodontitis (HR 1.45, 95% CI 1.14–1.85), gingivitis (HR 1.03, 95% CI 1.01–1.04), and periodontitis/gingivitis (HR 1.27, 95% CI 1.07–1.51). Furthermore, severe periodontal diseases showed a significantly increased risk of gastrointestinal cancer (HR 1.79, 95% CI 1.07–2.99). Results of sensitivity analyses for site-specific gastrointestinal cancers were robust with the main findings. In summary, periodontal diseases, especially severe periodontitis, increase the risk of overall and site-specific gastrointestinal cancers. Interventions to prevent and manage periodontal diseases may reduce the risk of developing gastrointestinal cancers. [ABSTRACT FROM AUTHOR]

The silver deposits located in the upper basin of the Felent Stream are currently the largest producing mine in the Türkiye. It is also significantly impacted by industrial, agricultural, and thermal spring-related waste in Kütahya Province. The main objectives of this study were to examine the spatiotemporal variations of 12 dissolved potentially toxic elements (PTEs) in the surface water of Felent Stream, to identify their possible sources, and to assess their probable risks. As a result of this study, among investigated PTEs, the highest mean concentrations of 3592–14,388 µg/L for Mg and the lowest of 0.15–0.19 µg/L for Cd were noted in Felent Stream water. The average concentrations of PTEs were found in the order of Mg > Ca > Na > As > Mn > B > Zn > Ni > Cu > Pb > Cr > Cd. Remarkably, during the dry season, there was a conspicuous escalation in the average PTEs contents of water, with an approximately multifold amplification. PTEs in stream water were evaluated for their potential ecotoxicological risks and possible sources. Based on ecological risk assessment indices, the stream exhibited low pollution levels during the wet season but displayed elevated pollution levels during the dry season, indicating a general shift towards heightened pollution conditions. The hazard index (HI) data for As exhibited significant potential noncarcinogenic risks across all monitoring stations. Conversely, the carcinogenic risk (CR) data underscored the imperative nature of addressing the health risks associated with As in the waters of the studied region. Mining activities were identified as the primary origin of PTEs based on principal component analysis (PCA). Moreover, upstream regions, proximal to the mining site, emerged as the most heavily contaminated areas according to cluster analysis (CA). [ABSTRACT FROM AUTHOR]

Background Lead (Pb) content in lipsticks and potential life-long exposure of which might cause severe effects in consumers are an important concern for public. Thus, studies emphasize that lead exposure has no safe levels. Methods From 10 different brands, in total, 25 solid, gloss and creamy lipsticks are deployed from Turkish markets that are also categorized in two different price ranges. In order to evaluate the blood Pb levels in children, the United States Environmental Protection Agency's 'Exposure Uptake Biokinetic Model' is utilized. To assess the health risk of chronic usage both for children and adults, oral daily systemic exposure levels are calculated with the worst-case scenario and are compared with Maximum Allowable Dose Level for lipsticks. For lifetime risk assessment, exposure is assumed to start by age 7, and four different exposure scenarios have been deployed. Results The mean lead content of lipsticks shows significant statistical differences between the high- and low-priced lipstick groups. Daily level and total risk for lifetime Pb exposure from deployed lipsticks are below the acceptable risk levels but long-worn usage of products with routine monitoring of metal content is crucial for sensitive and unintended exposure groups. [ABSTRACT FROM AUTHOR]

Polychlorinated Biphenyls (PCBs) represent organic contaminants that are persistent hazardous, carcinogenic, and genotoxic, thereby endangering both human well‐being and the ecosystem. This research delved into concentration patterns, sources, and health hazards associated with PCBs in dust collected from vehicle parks in Lagos metropolis. PCBs in samples of Lagos park dust extended from 1.00 to 36.80 ng/g, with PCB 18 exhibiting the highest mean concentration of 17.02 ng/g. Among the 12 PCBs studied, 5 Cl atom PCBs contributed the highest percentage, constituting 30% of the total PCB content in Lagos park dust. Dioxin‐like PCBs (DLPCBs) made up 27% of the overall PCBs composition in the dust. Using the positive matrix factorization method, eight sources of PCBs were identified, with biomass combustion contributing the highest proportion at 42% of the total PCB emissions. Health risk estimates revealed that the magnitude of PCBs exposure in human followed the order: ingestion > dermal contact > inhalation. PCBs exposure through ingestion in children was 9.33 times higher than that of adults, potentially attributed to the inadvertent intake of dust particles by children via hand‐to‐mouth contact. Cancer risk assessments for all PCB congeners remained below 10−6, indicating acceptable risk levels. PCB 18 had the highest cancer risk values, reaching 8.69 × 10−9 for children and 1.19 × 10−9 for adults. [ABSTRACT FROM AUTHOR]

Purpose: The relationship between vitamin intake and cancer risk in the chronic kidney disease (CKD) population is unknown. For this reason, we investigated the relationship between dietary vitamin intake and cancer risk in CKD patients and looked for effective vitamin dietary patterns. Methods: This study included 3518 CKD patients from 2007 to 2018 National Health and Nutrition Examination Survey database. All participants were categorized into four groups based on vitamin intake by K-mean clustering. The data were collected and analyzed from June 2023 to December 2023. Results: A total of 3518 CKD patients with a mean age of (61.8 ± 16.3) years were included in the study. During a median follow-up of 7.3 years, 137 participants died of cancer. In the multivariate adjusted cox proportional hazards model for single vitamin intake, vitamin E Q4 intake (reference Q1) reduced cancer mortality (HR (95% CI) = 0.45 (0.24–0.87), P = 0.018). Further plotting of the restricted cubic spline curve revealed a linearly decreasing relationship between vitamin E intake and cancer mortality (Poverall = 0.010 Pnon-linear = 0.163). In the multivariate adjusted cox proportional hazards model for multivitamin co-intake, the vitamin C/K intake group reduced cancer mortality compared to the low vitamin intake group (HR (95% CI) = 0.42 (0.20–0.88), P = 0.022). Conclusion: Increased vitamin C intake was independently associated with reduced cancer risk in CKD patients, and a vitamin dietary pattern with high vitamin C/K intake was also effective in reducing cancer risk. [ABSTRACT FROM AUTHOR]

AbstractWildfires can negatively impact the health and well-being of wildland firefighters through a variety of exposure pathways. Many studies have measured acute health effects from occupational exposure to pollutants in wildfire smoke; however, research specifically examining cancer risks from exposure to carcinogens is limited. This review aimed to better understand cancer risk in this occupation by assessing the existing evidence of exposures and summarizing measured concentrations of carcinogens among wildland firefighters. A systematic search was conducted to identify scientific papers using the following databases: Medline(OVID), Embase(OVID), PsycINFO(OVID), Cochrane Library, CINAHL(EBSCOHost), EconLit(EBSCOHost), Scopus, Agricultural and Environmental Science Collect(ProQuest), and NIOSHTIC-2. Forty-nine papers were identified that met eligibility criteria. Across the papers, 31 carcinogens were identified and quantified using a variety of assessment methods. Papers measured particulate matter (N = 26), polycyclic aromatic hydrocarbons (N = 12), volatile organic compounds (N = 14), crystalline silica (N = 5), black carbon (N = 4), asbestos (N = 3), radionuclides (N = 7), and metals (N = 2). Most papers measured inhalation exposures through traditional air sampling methods, but a subset of exposures to polycyclic aromatic hydrocarbons (N = 8), as well as heavy metals (N = 1), were measured through urinary biomarkers and naphthalene was measured using dermal wipe samples (N = 2). Although the heterogeneity of exposure assessment methods made direct comparison of concentrations difficult, the papers provide consistent evidence that wildland firefighters are regularly exposed to carcinogens. All wildland fire personnel should continue to implement recommended mitigation strategies and support new mitigations to reduce exposure to carcinogens on the job. [ABSTRACT FROM AUTHOR]

Background: BRCA1:c.5017_5019del (p.His1673del) is a founder variant relatively frequent in Northern Italy. Despite previous suggestion of pathogenicity, variant classification in public databases is still conflicting, needing additional evidence. Methods: Maximum likelihood penetrance of breast/ovarian and other cancer types was estimated using full pedigree data from 53 informative Italian families. The effect of the variant on BRCA1‐ABRAXAS1 interaction was assessed using a GFP‐fragment reassembly‐based PPI assay. Results were combined with additional data from multiple sources to classify the variant according to ACMG/AMP classification rules specified for BRCA1/2. Results: Variant‐carriers displayed increased risk for ovarian cancer (HR = 33.0, 95% CI = 7.0–155.0; cumulative risk at age 70 = 27.6%, 95% CI = 12.6–40.0%) but not for breast cancer (HR = 0.7, 95% CI = 0.2–2.2). An increased risk of uterine cancer (HR = 8.0, 95% CI = 1.03–61.6) emerged, warranting further evaluation. Likelihood‐ratio in favor of pathogenicity was 98898642.82 under assumption of standard BRCA1 breast and ovarian penetrance, and 104240832.84 after excluding breast cancer diagnoses (based on penetrance results). Functional analysis demonstrated that the variant abrogates the BRCA1‐ABRAXAS1 binding, supporting the PS3 code assignment within the ACMG/AMP rule‐based model. Collectively, these findings allowed to classify the variant as pathogenic. Conclusion: Pathogenicity of BRCA1:c.5017_5019del(p.His1673del) has been confirmed; however, breast cancer risk in Italian families is not increased, unlike in families from other countries and in carriers of most BRCA1 pathogenic variants. The knowledge of atypical risk profiles for this and other variants will pave the way for personalized management based on specific genotype. [ABSTRACT FROM AUTHOR]

Background: Gastroesophageal reflux disease (GERD) is a common condition characterized by the reflux of stomach contents into the esophagus. Despite its widespread prevalence worldwide, the causal link between GERD and various cancer risks has not been fully established, and past medical research has often underestimated or overlooked this relationship. Methods: This study performed Mendelian randomization (MR) to investigate the causal relationship between GERD and 19 different cancers. We leveraged data from 129,080 GERD patients and 473,524 controls, along with cancer-related data, obtained from the UK Biobank and various Genome-Wide Association Studies (GWAS) consortia. Single nucleotide polymorphisms (SNPs) associated with GERD were used as instrumental variables, utilizing methods such as inverse variance weighting, weighted median, and MR-Egger to address potential pleiotropy and confounding factors. Results: GERD was significantly associated with higher risks of nine types of cancer. Even after adjusting for all known risk factors—including smoking, alcohol consumption, major depression, and body mass index (BMI)—these associations remained significant, with higher risks for most cancers. For example, the adjusted risk for overall lung cancer was (OR, 1.23; 95% CI: 1.14–1.33), for lung adenocarcinoma was (OR, 1.18; 95% CI: 1.03–1.36), for lung squamous cell carcinoma was (OR, 1.35; 95% CI: 1.19–1.53), and for oral cavity and pharyngeal cancer was (OR, 1.73; 95% CI: 1.22–2.44). Especially noteworthy, the risk for esophageal cancer increased to (OR, 2.57; 95% CI: 1.23–5.37). Mediation analyses further highlighted GERD as a significant mediator in the relationships between BMI, smoking, major depression, and cancer risks. Conclusions: This study identifies a significant causal relationship between GERD and increased cancer risk, highlighting its role in cancer development and underscoring the necessity of incorporating GERD management into cancer prevention strategies. [ABSTRACT FROM AUTHOR]

The hydrosphere becomes contaminated secondarily by accumulated heavy metals in sediments which may be released into the aquatic environment, thereby increasing the risks to human health. To evaluate the pollution characteristics of heavy metals in surface water sediments of Ifite Ogwari, nine sediment samples were collected from surface water sources used by the residents for drinking and other household activities. The concentrations of eight heavy metals: cadmium (Cd), chromium (Cr), copper (Cu), Iron (Fe), manganese (Mn), nickel (Ni), lead (Pb) and zinc (Zn) were analyzed using Atomic Absorption Spectroscopy (AAS). Enrichment Factor (EF), Contamination Factor (CF), Geoaccumulation index (Igeo), Potential Ecological Risk Index (PERI) and Risk Assessment Code (RAC) were conducted. Results of heavy metal concentration indicated that Cu < Cr < Ni < Pb < Cd < Zn < Mn < Fe based on the average metal concentration. Human health assessment showed high cancer risk for children and adults in a ratio of 1 in 10000 population. PERI indicated that sediment samples from Iyiutu and Ahala streams have low potential ecological risk while samples from Ube, Tabasi and Ogbu showed moderate ecological risk whereas samples from Isiachala, Nabaloku and Atammele streams as well as Omambala river sediments were high. RAC shows no ecological risk by Zn, Pb, Ni, Cu and Mn but in Omambala river, Cr and Cd contributed to ecological risk while Fe contributed to ecological risk in all the samples. Consequently, there is need for proper monitoring from health base evaluation and conscious effort to live in a clean environment devoid of any kind of exposure. [ABSTRACT FROM AUTHOR]

In the oil and gas sector of Basrah, natural radioactive materials are accumulated in various equipment like wellheads, pumps, and separation vessels, often manifested as scales, sludge, and other forms of waste. Without proper preventive measures, these accumulations pose significant risks to workers, the public, and the environment. This study aims to assess the lifelong cancer risks associated with production processes and the handling of resultant waste, be it scale sediments, sludge, or soil. Sample collection across different regions was based on the evaluation of production and storage facilities. Using a high-purity germanium detector (HPGe), activity concentrations of 226Ra, 232Th, and 40K were measured. These concentrations were then used with standard equations to determine indoor effective dose rates. The regional-weighted (the lifetime risk of cancer is a measure of the cumulative risk of cancer over a specific age range and has a clear, intuitive appear) average of the lifetime excessive cancer risk was varied between (0.40 to 0.11 ×10-3) for ELCRoutdoor, (3.13 to 0.86 ×10-3) for ELCRindoor and (0.97 to 3 ×10-3) for ELCRtotal, significantly surpassing the global average value of (0.29x10-3). This disparity underscores the heightened risk posed by these activities, emphasizing the urgent need for enhanced safety measures and regulatory oversight to safeguard human health and the environment. [ABSTRACT FROM AUTHOR]

The objective of this study was to evaluate the extent of radon contamination in twenty-six drinking water samples from natural springs were collected from Dhirkot Azad Kashmir, along with four bottled mineral water samples. Radon gas escapes from the earth's crust due to uranium ores and diffuses into the atmosphere. This study assessed the levels of radon concentration, the yearly effective radiation dose, and carcinogenic risk from radon exposure in drinking water samples. The radon concentration varied from 0.28 to 30.25 Bq/L. The mean radon concentration of all samples was found to be 7.86 ± 2.3 Bq/L. The radon concentrations in bottled drinking water were found to be lower than those in natural springs. The statistical and GIS analyses included the use of interpolation and Pearson's correlation matrix. Seven samples had radon concentration that surpassed the standard limit established by the US-EPA, which is 11 Bq/L. The average annual effective dose from inhalation and ingestion was found to be lower than the value (0.1 mSv/y) provided by the WHO, but for some natural spring water samples, it exceeded the risk limit. The cancer risk revealed that 40% of the samples had an elevated lifetime cancer risk from radon exposure. Overall, the majority of the results obtained aligned with the worldwide guidelines established by the US-EPA. However, there were a few instances where the limits were exceeded, and constant monitoring is recommended. This study establishes a baseline for radon concentration in the area and provides a basis for future studies. [ABSTRACT FROM AUTHOR]

Breast cancer is a common cancer worldwide. Hyperplastic enlarged lobular units (HELUs) are common changes in the breasts of adult women. HELUs may be closely related to the occurrence and development of breast cancer. In this study, genes that are commonly contained in the expression profiles of the genomes of the two diseases and have significant differences in expression before and after the respective diseases were identified. Various enrichment analyses were performed according to the expression levels of these differentially expressed genes. Furthermore, LASSO regression analysis was performed on the differentially expressed genes to identify genes significantly related to survival. The optimal risk model for the survival of patients with breast cancer was established, and the accuracy of the model was verified on multiple data sets. A gene combination containing 17 genes was ultimately determined to be an independent prognostic factor. Kaplan‒Meier survival analysis demonstrated the good performance of this risk model. The study found that Shared Gene Signatures and Biological Mechanisms in Hyperplastic Enlarged Lobular Units and Breast Cancer, screened 17 important Shared Gene Signatures of Hyperplastic Enlarged Lobular Units which are closely related to the survival of breast cancer patients through machine learning, and established a prognosis model with high-accuracy, which is worthy of further exploration. [ABSTRACT FROM AUTHOR]

Due to rapid urbanization and industrial growth, groundwater globally is continuously deteriorating, posing significant health risks to humans. This study employed a comprehensive methodology to analyze groundwater in the Western Banat Plain (Serbia). Using Piper and Gibbs plots, hydrogeochemistry was assessed, while the entropy‐weighted water quality index (EWQI) was used to evaluate groundwater quality. Pollution sources were identified using positive matrix factorization (PMF) accompanied by Pearson correlation and hierarchical cluster analysis, while Monte Carlo simulation assessed health risks associated with groundwater consumption. Results showed that groundwater, mainly Ca–Mg–HCO3 type, is mostly suitable for drinking. Geogenic pollution, agricultural activities, and sewage were major pollution sources. Consumption of contaminated groundwater poses serious non‐carcinogenic and carcinogenic health risks. Additionally, arsenic from geogenic source was found to be the main health risks contributor, considering its worryingly elevated concentration, ranging up to 364 μg/L. These findings will be valuable for decision‐makers and researchers in managing groundwater vulnerability. Practitioner Points: Groundwater is severely contaminated with As in the northern part of the study area.The predominant hydrochemical type of groundwater in the area is Ca–Mg–HCO3.The PMF method apportioned three groundwater pollution sources.Monte Carlo identified rock dissolution as the primary health risk contributor.Health risks and mortality in the study area are positively correlated. [ABSTRACT FROM AUTHOR]

Background: Inborn Errors of Immunity (IEI) comprise several genetic anomalies that affect different components of the innate and adaptive responses, predisposing to infectious diseases, autoimmunity and malignancy. Different studies, mostly in adults, have reported a higher prevalence of cancer in IEI patients. However, in part due to the rarity of most of these IEI subtypes (classified in ten categories by the Primary Immunodeficiency Committee of the International Union of Immunological Societies), it is difficult to assess the risk in a large number of patients, especially during childhood. Objective: To document the cancer prevalence in a pediatric cohort from a single referral institution, assessing their risk, together with the type of neoplasia within each IEI subgroup. Method: An extensive review of clinical records from 1989 to 2022 of IEI patients who at some point developed cancer before the age of sixteen. Results: Of a total of 1642 patients with IEI diagnosis, 34 developed cancer before 16 years of age, showing a prevalence (2.1%) significantly higher than that of the general age matched population (0.22). Hematologic neoplasms (mostly lymphomas) were the most frequent malignancies. Conclusion: This study represents one of the few reports focused exclusively in pediatric IEI cases, describing not only the increased risk of developing malignancy compared with the age matched general population (a fact that must be taken into account by immunologists during follow-up) but also the association of the different neoplasms with particular IEI subtypes, thus disclosing the possible mechanisms involved. [ABSTRACT FROM AUTHOR]

• The study presents the first report of ATM :c.1564_1565del variant segregating with breast cancer and Ataxia-Telangiectasia (A-T) and in the same family. • This study highlights the importance of a comprehensive genomic investigation and appropriate cancer risk management of heterozygote carriers of ATM in families with A-T. • Given the age-related or moderate penetrance of ATM in breast cancer, ATM -positive family members of an affected individual with A-T are likely asymptomatic for breast or any other epithelial cancer. ATM gene is implicated in the development of breast cancer in the heterozygous state, and Ataxia-telangiectasia (A-T) in a homozygous or compound heterozygous state. Ataxia-telangiectasia (A-T) is a rare cerebellar ataxia syndrome presenting with progressive neurologic impairment, telangiectasia, and an increased risk of leukemia and lymphoma. Although the role of ATM, separately, in association with A-T and breast cancer is well documented, there is a limited number of studies investigating ATM variants when segregating with both phenotypes in the same family. Here, using joint analysis and whole genome sequencing, we investigated ATM c.1564_1565del in a family with one homozygous member presenting with A-T (OMIM # 208900) and three heterozygous members, of whom one had breast cancer (OMIM # 114480). To our knowledge, this is the first study of ATM c.1564_1565del segregation with both A-T and breast cancer phenotypes within the same kindred. This study highlights the need for a comprehensive genomic approach in the appropriate cancer risk management of heterozygote carriers of ATM in families with A-T. [ABSTRACT FROM AUTHOR]

Background: Observational studies have suggested that obstructive sleep apnea (OSA) may have a potential carcinogenic role. However, the results of these studies were inconsistent and the underlying genetic mechanisms have yet to be fully understood. Methods: We conducted a Mendelian randomization (MR) analysis using large-scale genome-wide association studies summary statistics to explore the possible causal effect of OSA on the risk of 16 specific-site cancers in the European population. Results: The MR analysis revealed a significantly negative correlation between OSA and the susceptibility to prostate cancer (OR: 0.87, 95%CI 0.79–0.95, p = 0.002) and a causal increase in the vulnerability to pancreatic malignancies (OR: 2.02, 95%CI 1.1–3.7, p = 0.02). However, no causal effects of OSA on other specific-site cancers were found. Sensitivity analyses demonstrated no significant heterogeneity or horizontal pleiotropy, thus validating the robustness of the original results. Conclusion: Our MR provided important insights into the causal associations between OSA and cancer risk, highlighting both protective and potentially harmful effects of OSA on different cancer types. [ABSTRACT FROM AUTHOR]

Background: Long-haul truck drivers (LHTDs) face a number of occupational hazards. One such hazard is exposure to diesel engine exhaust (DEE). However, this concept has yet to be analyzed. To address this gap, a concept analysis was conducted to explore the effects of DEE in relation to lung cancer. Methods: Walker and Avant's eight-step concept analysis method was utilized: concept selection, analysis purpose, concept uses, defining attributes, model case, borderline case, antecedents and consequences, and empirical referents. PubMed, Scopus, and CINAHL databases were searched for relevant literature. Findings: Diesel engine exhaust was identified as a mixture of gases and particulates that are considered carcinogenic. Defining attributes of DEE for truckers include respiratory effects such as decreased peak flow and increased airway resistance leading to symptoms such as a phlegm-producing cough, eye and throat irritation, exacerbation of asthma symptoms, and allergic responses. The identified level of DEE exposure associated with these attributes is 75 μg EC/m3 for 1 to 2 hours daily or a long-term exposure of 10 μg EC/m3. The conceptual definition of DEE in truckers was illustrated by the attributes, antecedents, consequences, model case, and empirical referents. Conclusion: Lung cancer was identified as a significant consequence of occupational DEE exposure for LHTDs. This analysis highlights the need for future research to develop interventions that will safeguard truckers from the adverse health effects of DEE exposure. [ABSTRACT FROM AUTHOR]

Eosinophils exhibit anti‐tumor cytotoxic responses in the tumor microenvironment and may contribute to tumor immunosurveillance. To assess the relationship between circulating eosinophils and cancer risk, we analyzed data from 443,542 adults aged 38–73 in the UK Biobank, who were initially cancer‐free, had over a year of follow‐up, and baseline white blood cell count measurements. Using multivariable Cox regression, we estimated hazard ratios (aHR) and 95% confidence intervals (95%CI) for each quartile increase in absolute eosinophil count (AEC) across 58 cancer types, adjusting for relevant confounders. During a median follow‐up of 5.8 years, 22,747 incident cancer cases were diagnosed. We observed an inverse association, which met Bonferroni significance, between AEC and overall cancer risk (aHR, 95%CI 0.97, 0.95–0.98). Notably, 16 cancer types showed borderline associations (p <.05) with AEC, with 12 types displaying an inverse relationship. These included four hematologic cancers (acute and other myeloid leukemia, other lymphocytic leukemia, and chronic lymphocytic leukemia/small lymphocytic lymphoma; aHR range; 0.58–0.87) and eight nonhematologic cancers (melanoma and nose/middle ear, soft tissue/heart, gum/other mouth, tongue, lung, colon, and breast cancers; aHR range: 0.65–0.95). Higher AEC showed a borderline significant association with increased risk for intrahepatic bile duct cancer, Hodgkin lymphoma, diffuse large B‐cell lymphoma, and chronic myeloid leukemia (aHR range: 1.13–1.42). Our study, the largest to date, provides insights into the relationship between blood eosinophils and a comprehensive list of incident cancers. The inverse association between AEC and overall cancer risk suggests a protective role for eosinophils in tumor surveillance. [ABSTRACT FROM AUTHOR]

Abstract Objective To investigate whether Molybdenum blood level is a marker of cancer risk on BRCA1 carriers. Methods A prospective cohort study was conducted among 989 initially unaffected women with a BRCA1 mutation. Blood samples were collected to measure molybdenum levels, and participants were followed for an average of 7.5 years. Cox proportional hazards models were used to assess the association between blood molybdenum levels and cancer incidence, adjusting for potential confounders. Results High blood molybdenum levels (> 0.70 µg/L) were significantly associated with an increased risk of developing ovarian cancer (HR = 5.55; 95%CI: 1.59–19.4; p = 0.007) and any cancer (HR = 1.74; 95%CI: 1.17–2.61; p = 0.007) but not breast cancer (HR = 1.46, CI = 0.91–2.33; p = 0.12). The cumulative incidence of ovarian cancer at ten years was 1.2% for the lowest molybdenum tertile, 4.2% for the middle tertile, and 8.7% for the highest tertile. Conclusion Elevated blood molybdenum levels are associated with an increased risk of ovarian cancer on BRCA1 mutation carriers. Lowering molybdenum levels may potentially reduce cancer risk in this population, and high molybdenum levels could serve as a marker for considering preventive oophorectomy in BRCA1 carriers. Further research is warranted to confirm these findings and explore interventions targeting molybdenum levels as a preventive measure for ovarian cancer in BRCA1 mutation carriers.

Abstract Background In Norway, we have offered testing of PMS2 since 2006, and have a large national cohort of carriers. The aim of this study was to describe all PMS2 variants identified, and to describe frequency, spectrum and penetrance of cancers in carriers of class 4/5 variants. Methods All detected PMS2 variants were collected from the diagnostic laboratories and reclassified according to ACMG criteria and gene specific guidelines. Data on variant, gender, cancer diagnosis, age at diagnosis, and age at last known follow-up was collected on all carriers of class 4/5 variants from electronic patient records. The Kaplan-Meier algorithm was used to calculate cumulative risk of any cancer, colorectal cancer and endometrial cancer. Results In total, 220 different PMS2 variants were detected. Twenty nine class 4/5 variants were identified in 482 carriers. The most common pathogenic variant was the founder mutation c.989-1G > T, detected in 204 patients from 58 families. Eighty seven out of 482 (18.0%) had been diagnosed with colorectal cancer, 10 of these (11.8%) before 40 years. Cumulative risk at 70 years in our cohort was 34.7% for colorectal cancer and 26.1% for endometrial cancer. Conclusions After 15 years of genetic testing, 29 different class 4/5 variants have been detected in Norway. Almost half of Norwegian PMS2 carriers have the founder variant 989-1G > T. Penetrance of colorectal cancer in our cohort was moderate but variable, as 11.5% of those diagnosed were younger than 40 years.

Abstract While selenium is a cofactor of several antioxidant enzymes against cancer and is essential for human health, its excess intake may also be harmful. Though a safe intake of selenium has recently been recommended, it is not well understood in the Asian population. We aimed to determine the association between dietary intake of selenium and cancer risk in a case–control study of 3758 incident cancer cases (i.e., stomach, colon, rectum, lung cancers, and other sites) and 2929 control subjects in Vietnam. Daily intake of selenium was derived from a semiquantitative food frequency questionnaire. The unconditional logistic regression model was used to calculate the odds ratios (ORs) and 95% confidence intervals (CIs) for the association between selenium intake and cancer risk. We observed a U-shaped association between selenium intake and cancer risk. A safe intake ranged from 110.8 to 124.4 µg/day (mean 117.8 µg/day). Compared to individuals with the safe intake of selenium, individuals with the lowest intake (i.e., 27.8–77.2 µg/day) were associated with an increased risk of cancer (OR = 3.78, 95% CI 2.89–4.95) and those with the highest intake (169.1–331.7 µg/day) also had an increased cancer risk (OR = 1.86, 95% CI 1.45–2.39). A U-shaped pattern of association between selenium intake and cancer risk was stronger among participants with body mass index (BMI)

Abstract Immunotherapy has emerged as a pivotal modality in cancer treatment, with immune checkpoint inhibitors effectively combating malignancies by impeding crucial pathways within the immune system and stimulating patients’ immune responses. Soluble forms of immune checkpoints exhibit a remarkable diversity and can be readily tracked in circulation, holding immense potential as biomarkers for cancer treatment. An increasing number of studies focused on soluble immune checkpoints in cancer have emerged thanks to technological advancements. In this systematic review, we comprehensively summarized the recent studies on soluble immune checkpoints in human cancer risk prediction, outcome prediction, therapeutic applications, and potential molecular mechanisms, which demonstrated the promising future of soluble immune checkpoints in clinical applications. The clinical relevance of soluble immune checkpoints has been recognized in multiple cancers, yet the therapeutic applications and mechanisms remain obscure. Interpreting the impacts and mechanisms of soluble immune checkpoints could shed a light on the novel strategies of cancer screening, treatments, and outcome prediction.

Abstract The hydrosphere becomes contaminated secondarily by accumulated heavy metals in sediments which may be released into the aquatic environment, thereby increasing the risks to human health. To evaluate the pollution characteristics of heavy metals in surface water sediments of Ifite Ogwari, nine sediment samples were collected from surface water sources used by the residents for drinking and other household activities. The concentrations of eight heavy metals: cadmium (Cd), chromium (Cr), copper (Cu), Iron (Fe), manganese (Mn), nickel (Ni), lead (Pb) and zinc (Zn) were analyzed using Atomic Absorption Spectroscopy (AAS). Enrichment Factor (EF), Contamination Factor (CF), Geoaccumulation index (Igeo), Potential Ecological Risk Index (PERI) and Risk Assessment Code (RAC) were conducted. Results of heavy metal concentration indicated that Cu

Abstract Background Gastroesophageal reflux disease (GERD) is a common condition characterized by the reflux of stomach contents into the esophagus. Despite its widespread prevalence worldwide, the causal link between GERD and various cancer risks has not been fully established, and past medical research has often underestimated or overlooked this relationship. Methods This study performed Mendelian randomization (MR) to investigate the causal relationship between GERD and 19 different cancers. We leveraged data from 129,080 GERD patients and 473,524 controls, along with cancer-related data, obtained from the UK Biobank and various Genome-Wide Association Studies (GWAS) consortia. Single nucleotide polymorphisms (SNPs) associated with GERD were used as instrumental variables, utilizing methods such as inverse variance weighting, weighted median, and MR-Egger to address potential pleiotropy and confounding factors. Results GERD was significantly associated with higher risks of nine types of cancer. Even after adjusting for all known risk factors—including smoking, alcohol consumption, major depression, and body mass index (BMI)—these associations remained significant, with higher risks for most cancers. For example, the adjusted risk for overall lung cancer was (OR, 1.23; 95% CI: 1.14–1.33), for lung adenocarcinoma was (OR, 1.18; 95% CI: 1.03–1.36), for lung squamous cell carcinoma was (OR, 1.35; 95% CI: 1.19–1.53), and for oral cavity and pharyngeal cancer was (OR, 1.73; 95% CI: 1.22–2.44). Especially noteworthy, the risk for esophageal cancer increased to (OR, 2.57; 95% CI: 1.23–5.37). Mediation analyses further highlighted GERD as a significant mediator in the relationships between BMI, smoking, major depression, and cancer risks. Conclusions This study identifies a significant causal relationship between GERD and increased cancer risk, highlighting its role in cancer development and underscoring the necessity of incorporating GERD management into cancer prevention strategies.

In this study, the activity concentrations of gross alpha and gross beta in 125 drinking water samples (16 tap and 109 spring waters) collected from Ankara province were measured using a gas proportional α/β counter. The average (range) activity concentrations of gross alpha and gross beta were determined as 105 (20–495) mBqL−1 and 195 (70–850) mBqL−1, respectively. Average annual effective dose to adults caused by ingestion of water samples was estimated as 74.1 ± 43.2 µSv y−1. The average estimated cancer risk value depending on irradiations was calculated as 3.8 × 10−4 and 2.6 × 10−4 for the region using the nominal probability coefficients recommended by ICRP 60 and ICRP 103, respectively. Annual effective dose values in 10.4% of samples exceeded the limit values suggested by WHO for drinking waters in terms of beta activity and this was 0.8% for alpha activity. Moreover, contribution of 40K to the gross beta activity in drinking waters of the region was determined as 47%. [ABSTRACT FROM AUTHOR]