UNASSIGNED: Observational investigations have examined the impact of glucosamine use on the risk of cancer and non-neoplastic diseases. However, the findings from these studies face limitations arising from confounding variables, reverse causation, and conflicting reports. Consequently, the establishment of a causal relationship between habitual glucosamine consumption and the risk of cancer and non-neoplastic diseases necessitates further investigation.
UNASSIGNED: For Mendelian randomization (MR) investigation, we opted to employ single-nucleotide polymorphisms (SNPs) as instruments that exhibit robust associations with habitual glucosamine consumption. We obtained the corresponding effect estimates of these SNPs on the risk of cancer and non-neoplastic diseases by extracting summary data for genetic instruments linked to 49 varied cancer types amounting to 378,284 cases and 533,969 controls, as well as 20 non-neoplastic diseases encompassing 292,270 cases and 842,829 controls. Apart from the primary analysis utilizing inverse-variance weighted MR, we conducted two supplementary approaches to account for potential pleiotropy (MR-Egger and weighted median) and assessed their respective MR estimates. Furthermore, the results of the leave-one-out analysis revealed that there were no outlying instruments.
UNASSIGNED: Our results suggest divergence from accepted biological understanding, suggesting that genetically predicted glucosamine utilization may be linked to an increased vulnerability to specific illnesses, as evidenced by increased odds ratios and confidence intervals (95% CI) for diseases, such as malignant neoplasm of the eye and adnexa (2.47 [1.34-4.55]), benign neoplasm of the liver/bile ducts (2.12 [1.32-3.43]), benign neoplasm of the larynx (2.01 [1.36-2.96]), melanoma (1.74 [1.17-2.59]), follicular lymphoma (1.50 [1.06-2.11]), autoimmune thyroiditis (2.47 [1.49-4.08]), and autoimmune hyperthyroidism (1.93 [1.17-3.18]). In contrast to prior observational research, our genetic investigations demonstrate a positive correlation between habitual glucosamine consumption and an elevated risk of sigmoid colon cancer, lung adenocarcinoma, and benign neoplasm of the thyroid gland.
UNASSIGNED: Casting doubt on the purported purely beneficial association between glucosamine ingestion and prevention of neoplastic and non-neoplastic diseases, habitual glucosamine ingestion exhibits dichotomous effects on disease outcomes. Endorsing the habitual consumption of glucosamine as a preventative measure against neoplastic and non-neoplastic diseases cannot be supported.

Human UDP-glycosyltransferases (UGTs) are responsible for the glucuronidation of a wide variety of endogenous substrates and multiple commonly prescribed drugs. Different genetic polymorphisms in UGT genes are implicated in interindividual differences in drug response and cancer risk. However, the genetic complexity beyond these variants has not been comprehensively assessed. We here leveraged whole-exome and whole-genome sequencing data from 141,456 unrelated individuals across seven major human populations to provide a comprehensive profile of genetic variability across the human UGT gene family. Overall, 9666 exonic variants were observed of which 98.9% were rare. To interpret the functional impact of UGT missense variants, we developed a gene family-specific variant effect predictor. This algorithm identified a total of 1208 deleterious variants, most of which were found in African and South Asian populations. Structural analysis corroborated the predicted effects for multiple variations in substrate binding sites. Combined, our analyses provide a systematic overview of UGT variability, which can yield insights into inter-individual differences in phase 2 metabolism and facilitate the translation of sequencing data into personalized predictions of UGT substrate disposition.

Vitamin B12 (B12) is a molecule involved in several biological. Abnormally high levels are frequently found, but their causes can be multiple, and consequences have not been clearly elucidated. The objective of this review was to summarize the current evidence on the associations of elevated B12 and the development of cancer, and all-cause mortality in adults. Six references looking at mortality and seven looking at cancer risk were included. The evidence suggests an association between elevated B12 with a higher risk of cancer, with risk ratios ranging 1,88 to 5,9. There was less consistent evidence linking vitamin B12 and mortality.
Elevated B12 levels exceeding 1000 pg/L, if sustained and unexplainable, warrant a comprehensive individual assessment of each patient. This evaluation should encompass various potential factors contributing to the elevation, aiming to effectively guide the diagnostic process of neoplastic diseases.Clinical longitudinal observational studies have suggested a potential link between heightened B12 levels and the risks of cancer and mortality. Nonetheless, these studies have been retrospective cohort studies, and lack a defined threshold point of B12 levels.Studies have documented a positive correlation between elevated levels of B12 and the incidence of lung, pancreatic, and liver cancers, as well as certain hematological neoplasms, particularly those related to the myeloid lineage. Conversely, a consistent negative association has been observed in the context of breast cancer. Findings concerning neoplasms of the lower gastrointestinal tract and prostate display contradictory outcomes.The diagnostic significance of elevated B12 levels among patients already diagnosed with cancer remains uncertain and could potentially be linked to reverse causality.

Lynch syndrome (LS) is an inherited cancer predisposition disorder associated with an elevated risk of developing various solid cancers, but mostly colorectal cancer (CRC). Despite having the same germline pathogenic variant (PV) in one of the mis-match repair genes or the EPCAM gene, Lynch syndrome variant heterozygotes (LSVH) exhibit a remarkable phenotypic variability in the risk of developing cancer. The role of human leukocyte antigen (HLA) in modifying cancer development risk prompted our hypothesis into whether HLA variations act as potential genetic modifiers influencing the age at cancer diagnosis in LSVH. To investigate this, we studied a unique cohort of 426 LSVH carrying the same germline PV in the hMLH1 gene (MLH1:c.1528C > T) in South Africa. We intuitively selected 100 LSVH with the greatest diversity in age at cancer diagnosis (N = 80) and the oldest cancer unaffected LSVH (N = 20) for a high-throughput HLA genotyping of 11 HLA class I and class II loci using the shotgun next-generation sequencing (NGS) technique on the Illumina MiSeq platform. Statistical analyses employed Kaplan-Meier survival analyses with log-rank tests, and Cox proportional hazards using binned HLA data to minimize type I error. Significant associations were observed between young age at cancer diagnosis and HLA-DPB1*04:02 (mean age: 37 y (25-50); hazard ratio (HR) = 3.37; corrected p-value (q) = 0.043) as well as HLA-DPB1 binned alleles (including HLA-DPB1*09:01, HLA-DPB1*10:01, HLA-DPB1*106:01, HLA-DPB1*18:01, HLA-DPB1*20:01, HLA-DPB1*26:01, HLA-DPB1*28:01, HLA-DPB1*296:01, and HLA-DPB1*55:01) (mean age: 37 y (17-63); HR = 2.30, q = 0.045). The involvement of HLA-DPB1 alleles in the age at cancer diagnosis may highlight the potential role of HLA class II in the immune response against cancer development in LSVH. When validated in a larger cohort, these high-risk HLA-DPB1 alleles could be factored into cancer risk prediction models for personalized cancer screening in LSVH.

BACKGROUND: Elastic stable intramedullary nailing (ESIN) is a well-defined and appropriate treatment of choice for long bone fractures. Despite its benefits, the risk of cancer from imaging devices is of particular concern for younger adults. So, this survey was conducted to estimate the doses administered to patients undergoing ESIN of long bone fractures utilizing a 2-dimensional (2D) C-arm fluoroscopy machine during surgery, as well as the carcinogenic risk associated with the use of the machine.
METHODS: This study was conducted on 147 patients who required ESIN for long-bone fractures. Patients\' demographic data, surgical data and imaging information were collected. For each patient, the organ doses and the effective doses were computed with the Monte Carlo PCXMC 2.0 simulation software. The cancer risk models proposed in the Biological Effects of Ionizing Radiation VII (BEIR VII) Phase 2 report were used to evaluate the risk of exposure-induced cancer death (REID) values.
RESULTS: For all patients, the highest organ dose was delivered to the gonads. The mean effective dose was 0.026 ± 0.015 mSv and 1.3E-04 ± 1E-04 mSv for ESIN of femur and tibia fractures, respectively. Males had a mean REID of 1 per million, while females had a mean REID of 0.19 per million. The younger males had considerably higher REID values. The effective dose was significantly correlated with age, gender, and irradiation time.
CONCLUSIONS: Low levels of effective doses and cancer risks associated with the utilization of the fluoroscopy machine in current practice were found in ESIN treatment of long-bone fractures.
CONCLUSIONS: This outcome will help to raise surgeons\' awareness of radiation risks and encourage them to initiate measures to keep radiation dose and exposure time as low as reasonably achievable.

BACKGROUND: The IDENTIFY study developed a model to predict urinary tract cancer using patient characteristics from a large multicentre, international cohort of patients referred with haematuria. In addition to calculating an individual\'s cancer risk, it proposes thresholds to stratify them into very-low-risk (<1%), low-risk (1-<5%), intermediate-risk (5-<20%), and high-risk (≥20%) groups.
OBJECTIVE: To externally validate the IDENTIFY haematuria risk calculator and compare traditional regression with machine learning algorithms.
METHODS: Prospective data were collected on patients referred to secondary care with new haematuria. Data were collected for patient variables included in the IDENTIFY risk calculator, cancer outcome, and TNM staging. Machine learning methods were used to evaluate whether better models than those developed with traditional regression methods existed.
METHODS: The area under the receiver operating characteristic curve (AUC) for the detection of urinary tract cancer, calibration coefficient, calibration in the large (CITL), and Brier score were determined.
CONCLUSIONS: There were 3582 patients in the validation cohort. The development and validation cohorts were well matched. The AUC of the IDENTIFY risk calculator on the validation cohort was 0.78. This improved to 0.80 on a subanalysis of urothelial cancer prevalent countries alone, with a calibration slope of 1.04, CITL of 0.24, and Brier score of 0.14. The best machine learning model was Random Forest, which achieved an AUC of 0.76 on the validation cohort. There were no cancers stratified to the very-low-risk group in the validation cohort. Most cancers were stratified to the intermediate- and high-risk groups, with more aggressive cancers in higher-risk groups.
CONCLUSIONS: The IDENTIFY risk calculator performed well at predicting cancer in patients referred with haematuria on external validation. This tool can be used by urologists to better counsel patients on their cancer risks, to prioritise diagnostic resources on appropriate patients, and to avoid unnecessary invasive procedures in those with a very low risk of cancer.
RESULTS: We previously developed a calculator that predicts patients\' risk of cancer when they have blood in their urine, based on their personal characteristics. We have validated this risk calculator, by testing it on a separate group of patients to ensure that it works as expected. Most patients found to have cancer tended to be in the higher-risk groups and had more aggressive types of cancer with a higher risk. This tool can be used by clinicians to fast-track high-risk patients based on the calculator and investigate them more thoroughly.

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.

This paper investigates the relationship between periodontal disease and various cancer types. It provides a comprehensive overview of the existing knowledge about the interaction between periodontal disease and carcinogenesis, explores the underlying biological mechanisms of this connection, and consider the impact of these findings on healthcare practices and future research directions. Utilizing Systematic Literature Network Analysis, which combines bibliometric analysis with Systematic Literature Review, this study analyzes 164 documents from 2000 to 2023. Focus is placed on the 38 most globally cited papers, enabling a targeted and comprehensive analysis of the predominant research within this scope. This review highlights that colorectal, oral, pancreatic, lung, and gastrointestinal cancers have consistent associations with periodontal disease. On the other hand, hematological, breast and prostate cancers show associations with periodontal disease, but these links are less pronounced and more variable, indicating the need for targeted research in these domains. These insights emphasize the necessity for a multidisciplinary healthcare approach, recognizing the systemic implications of periodontal disease.

BACKGROUND: The use of protein supplements by athletes has risen due to their effectiveness in meeting dietary needs. However, there is a growing concern about the presence of potentially toxic metals (PTMs. Al, Cr, Mn, Ni, Cu, Zn, Cd, and Pb) in these supplements. Consequently, it is crucial to evaluate the levels of these PTMs to ensure the safety of the supplements.
METHODS: The objective of the current study was to assess the PTMs concentrations in protein supplements and examine any possible health hazards. Twenty-five samples of protein supplements were purchased from different pharmacies to screen them for metals. Inductively coupled plasma-optical emission spectrometry (ICP-OES) was utilized to analyze metal content. Additionally, chemometric methods such as Pearson\'s correlation coefficient (PCC), principal component analysis (PCA), and hierarchical cluster analysis (HCA) were employed to identify possible sources of PTMs contamination in protein supplements.
RESULTS: Concentration ranges for PTMs were found as, Al (0.03-3.05 mg/kg), Cr (0.11-0.89 mg/kg), Mn (1.13-8.40 mg/kg), Ni (0.06-0.71 mg/kg), Cu (1.05-5.51 mg/kg), Zn (2.14-27.10 mg/kg), Cd (0.01-0.78 mg/kg), and Pb (0.06-0.57 mg/kg). The weekly intake of Cd exceeded the level of tolerable weekly intake (TWI) set by the European Food Safety Authority (EFSA).
CONCLUSIONS: Athletes, bodybuilders, fitness enthusiasts, dieters, young adults and adolescents, and health-conscious individuals should be conscious of Cd concentration as it does not compliance the TWI set by EFSA. Target hazard quotient (THQ < 1), hazard index (HI < 1), margin of exposure (MOE ≥ 1), percentile permitted daily exposure (% PDE < 100), and cumulative cancer risk (CCR < 1 × 10-3) analyses revealed that there are no appreciable non-carcinogenic and carcinogenic health risks associated with the use of these products.

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