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PubMed2026

Three-Dimensional Fracture Mapping of the Terrible Triad of the Elbow: Morphological Characteristics and Clinical Implications.

BACKGROUND: The morphology of fractures in the terrible triad of the elbow (TTE) is complex, and precise management relies on a profound understanding of this morphology. This study aims to systematically analyze, for the first time, the distribution and morphological characteristics of TTE fracture lines using three-dimensional (3D) imaging technology. METHODS: Clinical data and thin-slice CT scans of 112 patients with TTE from January 2021 to December 2024 were retrospectively included. 3D fracture models were reconstructed using Mimics software. Virtual reduction and standardized alignment were performed using 3-matic software. Fracture lines were mapped onto standard ulnar and radial templates, and 3D fracture heat maps were generated using the E-3D software to demonstrate the high-frequency distribution zones of the fracture lines visually. Statistical analysis was performed using SPSS software (version 21.0, IBM Corp., Armonk, NY, USA). Continuous variables were compared using one-way analysis of variance (ANOVA), and categorical variables were compared using the chi-square test (χ2 test). A two-tailed p < 0.05 was considered statistically significant. RESULTS: The study revealed distinct patterns in the distribution of TTE fracture lines. In the coronoid process, the fracture "hot zone" presented as an annular high-density band extending from the lateral middle aspect to the tip. In the radial head, an oblique high-density band was observed in the anterolateral quadrant of the articular surface. The radial neck exhibited a circumferential high-density zone, which was most prominent in the anterolateral aspect. Statistical analysis indicated a significant correlation between age and fracture complexity; the proportion of Regan-Morrey type III coronoid fractures and Mason type III radial head fractures was significantly higher in elderly patients (> 60 years) (p < 0.05), suggesting that advanced age is a significant risk factor for complex fractures. CONCLUSION: This study is the first to visually reveal the Collaborative Distribution Patterns of TTE fracture lines using 3D fracture mapping technology. This model provides morphological evidence for understanding the injury mechanism of TTE and offers an anatomical framework that may assist surgeons in individualizing surgical approaches and fixation strategies.

Humans↗

PubMed2026

Distinct mutational landscapes for germline and somatic cancer variants in forty tumor suppressor genes.

Germline and somatic cancer variants in tumor suppressor genes (TSGs) share loss-of-function mechanisms, but studies of a few genes (DICER1 and CEBPA) have demonstrated differences in variant consequence and location. To systematically assess whether TSGs display distinct mutational patterns, we leveraged large public genetic databases and compared 32,941 high-quality pathogenic/likely pathogenic (P/LP) germline variants in ClinVar, with 12,907 oncogenic/likely oncogenic (O/LO) somatic tumor variants from cBioPortal across 40 TSGs. Only 3,863 (9.2%) variants were shared. Eighteen TSGs showed significantly different distributions of variant occurrences by molecular consequence, replicated with non-overlapping somatic data from the COSMIC database (chi-squared tests, false discovery rate = 5%). DICER1, TP53, and SMAD4 displayed excess somatic missense events, while nine TSGs (e.g., RB1 and APC) contained excess somatic stop-gain events throughout the coding sequence. Analysis by tumor type revealed excess stop-gain events in tissues exposed to environmental mutagens with corresponding mutation signatures. For several TSGs (WT1), germline variants predispose to tumors (Wilms' tumor) distinct from the majority source of somatic data (myeloid leukemia). Germline and somatic events are also distributed unevenly across cDNA locations, with 103 regions of preferential clustering in 39 TSGs (78 somatic and 25 germline). Twenty somatic clusters contained recurring frameshifts in homopolymer runs, many in tumors with microsatellite instability. Germline clusters contain more germline-exclusive variants, some driving non-cancer phenotypes reflecting genetic pleiotropy. Altogether, germline and somatic variants of TSGs represent unique sets with substantially different patterns shaped by selection pressures from gene-specific and somatic mutational mechanisms. Characterizing these distinctions enables more accurate clinical interpretation of TSG variants.

Humans↗

PubMed1977

Caries experience in orthodontically treated individuals.

The caries ecperience in 26 girls and 26 boys living on an island outside. Bergen, who had received orthodontic treatment with fixed appliances, was examined 1.5 to 2 years after the end of treatment. The children were then between 1l and 17 years old. The remaining children of the same age group, 58 girls and 53 boys, served as controls. The orthodontic patients had received repeated hygiene instructions during the treatment period and were expected to rinse their mouth with 0.05% sodium fluoride daily. The percentage distribution of DMF-surfaces indicated somewhat less caries experience in the treated group. A chi-square test showed significantly more intact surfaces on the maxillary first molars, second premolars, canines and central incisors, and mandibular molars and second premolars in treated than in untreated children, and also demonstrated significantly fewer new lesions in the upper second molars at the time of examination in the treated groups. A comparison of the caries experience of the different surfaces revealed significantly more intact surfaces in the treated group and significantly fewer new lesions on the mesial and distal surfaces in treated in untreated children at the time of examination.

Adolescent↗

PubMed1978

Use of the beta-binomial distribution in dominant-lethal testing for "weak mutagenic activity: part 2.

Experiments in Dominant-Lethal Testing have been simulated on the computer to estimate the type I error rates and the power of the Beta-Binomial test under various models. (1) The mating ratio is one; and p, the probability that an implant will die, is distributed over the couples. (2) The mating ratio is larger than one; and p is distributed over the males, the females mated to the same male being binomial observations of the value p supplied by the male. (3) The mating ratio is larger than one; and p is distributed over the females. The average rates of dead implants have been set at 0.08 and 0.10 for the control and treatment groups, respectively, and a nominal level of significance equal to 0.05 has been chosen. The type I error rate of the traditional chi-square test has also been estimated. A by-product of these simulations is the behaviour of the estimates alpha and beta of the beta-distribution parameters, which discloses that, in the actual experiments with mice, p is distributed over the females. Our results lead to the recommendations that, for a given number of animals per group, a mating ratio larger than one should be adopted and that the males should be considered as the experimental units for the calculations. With 300 and 450 animals per group, average powers of 0.72 and 0.85 are reached, respectively, for the chosen increment of 2% in the rate of dead implants. Under these models, the type I error rate of the traditional chi-square test may grow to 0.30 for the nominal level of 0.05.

Genes, Dominant↗

PubMed1979

Influence of a between-run component of variation, choice of control limits, and shape of error distribution on the performance characteristics of rules for internal quality control.

A computer-stimulation study has been performed to determine how the performance characteristics of quality-control rules are affected by the presence of a between-run component of variation, the choice of control limits (calculated from within-run vs. total standard deviations), and the shape of the error distribution. When a between-run standard deviation (Sb) exists and control limits are calculated from the total standard deviation (St, which includes Sb as well as the within-run standard deviation, Sw), there is generally a loss in ability to detect analytical disturbances or errors. With control limits calculated from Sw, there is generally an increase in the level of false rejections. The presence of non-gaussian error distribution appears to have considerably less effect. It can be recommended that random error be controlled by use of a chi-square or range-control rule, with control limits calculated from Sw. Optimal control of systematic errors is difficult when Sb exists. An effort should be made to reduce Sb, and this will lead to increased ability to detect analytical errors. When Sb is tolerated or accepted as part of the baseline state of operation for the analytical method, then further increases in the number of control observations will be necessary to achieve a given probability for error detection.

Chemistry, Clinical↗

PubMed1977

Is there an association between astrological data and personality?

A test was made of the hypothesis that personality characteristics can be predicted on the basis of various features of the individual's astrological chart. Astrological charts were prepared for 196 college-age Ss who also were administered the MMPI and the Leary Interpersonal Check List. Ss were divided into those who had extreme scores on any of the 13 personality variables studied and those who did not. For each personality variable, comparisons were made on a large number of astrological dimensions between distributions of Ss with and without extreme test scores. Six hundred thirty-two such comparisons were made and evaluated with chi-square tests. In that the obtained number of statistically significnat chi-squares was less than what would be expected on a chance basis, the hypothesis was rejected.

Astrology↗

PubMed1977

Evaluation of the non-randomness of protein compositions.

A method is described for assessing the non-randomness of protein compositions, based on the chi-squared statistic for the differences between the observed numbers of residues of each type and the numbers expected for a random distribution of codons. The analysis indicates that changes in at least 30% of the residues in natural proteins are selected against.

Amino Acids↗

PubMed1979

Birth order and parental age in microphthalmos and other ocular diseases.

We compared the distribution of birth order and maternal and paternal ages of blind school children throughout Japan with that of the total Japanese population of the corresponding age groups and with that of a subgroup of children with acquired blindness. The number of first-born children with microphthalmos was smaller, and the number of second-, third-, or fourth-born children was larger, as compared with the control groups. The differences were highly statistically significant by chi-square test. There was a less pronounced indication of birth order effect in amblyopia, congenital cataract, and optic nerve atrophy, which involved more first-borns than in the controls. The distribution of maternal age was also different from the control group in microphthalmos, congenital cataract, corneal opacity, and optic nerve atrophy. Less mothers in their 20s and more in their 30s produced children with these conditions. We believe this finding may be partly related to the rapid decline in infant mortality and in the incidence of congenital blindness in Japan.

Adult↗

PubMedDate not supplied

Genetic polymorphism of ABO and Rh system in relation to bronchial asthma: preliminary report.

115 asthmatic children and 1001 healthy voluntary blood donors were studied in order to determine the distribution of blood groups among them. Gene frequencies were also calculated in asthmatic patients and controls. No difference was noted between Rh system in both groups; but the ABO system showed an excess of blood group A among asthmatic patients. Gene frequency of A (p) and gene frequency of O (r) was quite different too for asthmatics and controls. No difference was noted in blood groups B and AB; nor in the gene frequency of B(q). The difference in the distribution of blood group A and O between control and asthmatic groups was found to be highly significant (P less than 0.02) with the chi-square test.

ABO Blood-Group System↗

PubMed2025

Association of Calpain-10 gene polymorphisms with Type 2 diabetes mellitus: a case-control study from a tertiary care hospital in Pakistan.

INTRODUCTION: Type 2 diabetes mellitus (T2DM) is a major public health challenge, with rising prevalence in low- and middle-income countries such as Pakistan. Genetic susceptibility plays a critical role in its pathogenesis. Calpain-10 (CAPN-10), a gene implicated in insulin secretion and glucose homeostasis, has been studied for its potential involvement in T2DM. This study aimed to evaluate the association of CAPN-10 polymorphisms-SNP44 (rs2975760) and SNP43 (rs3792267)-with T2DM in a Pakistani cohort. METHODS: This case-control study included 164 T2DM patients and 164 healthy controls (mean age ± SD: 57.2 ± 8.2 vs. 53.9 ± 6.3 years; age range: 41-82 years). The male-to-female ratio was 41.4-58.6% in cases and 37.2-62.8% in controls. Participants were enrolled using non-probability convenience sampling. Genomic DNA was extracted from whole blood, and genotyping of CAPN-10 SNPs (rs3792267 and rs2975760) was performed using PCR-RFLP. Genotype distributions were assessed for Hardy-Weinberg equilibrium. Associations with T2DM were evaluated using odds ratios (ORs) and 95% confidence intervals (CIs) via logistic regression. Chi-square tests were used for categorical comparisons, with p < 0.05 considered statistically significant. Analyses were conducted using SPSS version 26. RESULTS: For SNP44, no significant association with T2DM was observed under dominant, heterozygous, or recessive models after Bonferroni correction (adjusted p > 0.05). Similarly, SNP43 showed no statistically significant association with T2DM in either dominant or recessive models (adjusted p > 0.05), although the AA genotype appeared more frequently among T2DM cases. These findings suggest no significant role of CAPN-10 polymorphisms in T2DM susceptibility in this population. CONCLUSION: CAPN-10 polymorphisms SNP44 and SNP43 showed no significant association with T2DM in this population, suggesting limited predictive value for disease susceptibility.

Humans↗

PubMedDate not supplied

A preliminary report of mortality patterns among foundry workers.

A proportional mortality study was conducted utilizing the death records maintained from 1971 to 1975 by the International Molders and Allied Workers Union as part of a death benefits program. Death certificates were obtained on 3,013 members of the study group and classified according to the 8th Revision of the ICA by a trained nosologist. The ate- and race-specific cause distribution of all deaths among males in the United States for 1973 were used as a standard from which expected deaths were calculated. The statistical significance of differences between observed and expected numbers of deaths was determined by a chi-square test. The most statistically significant finding in this study was an excess lung cancer mortality (208 observed vs. 142 expected) and an excess mortality due to pneumoconiosis (29 observed vs. 5 expected). A discussion is included of the potential agents found in the foundry environment that may be responsible for the increased lung cancer risk.

Adult↗

PubMed2026

Are we Prepared? Genetic Counseling for Stillbirth in the Sequencing Era.

Stillbirth affects approximately 1 in 175 pregnancies annually in the United States. Although the American College of Obstetricians and Gynecologists recommends genetic testing as part of the stillbirth evaluation, families often face barriers to obtaining a complete evaluation. Expansion of the diagnostic evaluation of stillbirth is expected to include exome/genome sequencing, with preliminary studies demonstrating its diagnostic utility. Consequently, genetic counselors (GCs) are expected to play an expanding role in post-stillbirth care. This study explored current genetic counseling practices for stillbirth and GCs' preparedness to support patients in this setting. A cross-sectional survey was distributed across four channels. Eligible participants included GCs in the United States and Canada with at least 1 year of prenatal experience. The survey assessed GC frequency and timing in stillbirth counseling, genetic testing practices, comfort addressing psychosocial needs, and perceived barriers to care. Responses were analyzed using descriptive statistics. Group comparisons were performed using Chi-square and Fisher's exact tests. Open-ended responses were coded for themes. Seventy-one responses were analyzed. Approximately half of respondents (49.3%, n = 36) reported "never/very rarely/rarely" counseling patients postpartum, despite this being the optimal time to offer genetic testing. Delivering providers (46.5%, n = 33) were often responsible for informing patients about testing and obtaining consent, compared to GCs (11.3%, n = 8). Although chromosomal microarray (CMA) is recommended as the standard of care (SOC), 12.7% (n = 9) of GCs reported not offering CMA for anomalous and non-anomalous stillbirths. Perceived barriers to SOC testing included reported lack of obstetrician awareness (91.5%, n = 65) and challenges coordinating specimen collection (90.1%, n = 64). These findings highlight barriers to SOC genetic evaluation and underscore the need to strengthen institutional protocols, enhance provider education, and develop stillbirth-specific genetic counseling guidelines. GC involvement in these efforts will be essential to promoting equitable access to comprehensive post-stillbirth care as sequencing becomes integrated into practice.

Humans↗

PubMed2026

Analysis of genetic polymorphisms and mRNA expression of DRD3 and HTR2A in bruxism.

BACKGROUND: Bruxism, characterized by the involuntary grinding or clenching of teeth, is influenced by genetic, psychological, and environmental factors. This study aimed to evaluate the role of DRD3 (rs6280) and HTR2A (rs6313) polymorphisms in bruxism and to investigate the expression of these genes to better understand their biological significance. METHODS: This case-control study included 82 bruxism patients and 87 controls. Diagnosis was based on clinical examination and non-instrumental criteria from the 2018 international consensus. Genotyping of HTR2A rs6313 and DRD3 rs6280 was performed using PCR-RFLP, and gene expression in peripheral blood was assessed by qPCR. Statistical analyses included chi-square tests, logistic regression, and mRNA expression analysis using the ΔΔCt method. RESULTS: A significant association was identified between bruxism and the rs6313 polymorphism of the HTR2A gene (p = 0.004; OR = 1.89 [1.23-2.92]), with the C allele associated with increased risk. Moreover, HTR2A mRNA expression was upregulated in individuals with bruxism. While no significant differences were observed in DRD3 rs6280 genotype distribution between cases and controls, the presence of the C allele appeared to increase susceptibility to sleep bruxism. In addition, DRD3 mRNA expression was downregulated in bruxism patients. CONCLUSIONS: These findings highlight a significant association between bruxism and the rs6313 polymorphism of the HTR2A gene. Furthermore, increased HTR2A and decreased DRD3 expression support the involvement of serotonin and dopamine pathways in bruxism etiology, underscoring its multifactorial and complex nature. CLINICAL SIGNIFICANCE: This study elucidates the genetic basis of bruxism, indicating a potential role of serotonin and dopamine signaling in its pathogenesis. Understanding genetic predisposition could aid in early detection, risk assessment, and targeted treatment development. TRIAL REGISTRATION: Clinicaltrials.gov ; trial registration number: NCT06457646 (13/06/2024).

Adult↗

PubMed1977

Distribution of DSM-II diagnoses in a child psychiatric setting.

While DSM-II contains more diagnostic categories related specifically to children than did the earlier DSM-I, clinical utilization studies of the various categories have not been extensive. The present study reports data on the distribution of diagnoses of childhood disorders and analyzes relationships among several diagnostic categories and subject variables. Results indicate that clinicians are using a wide range of DSM-II diagnoses for childhood disorders, including some which were intended for use with adults as well as those which were designed specifically for children. Transient Situational Disorders and Behavior Disorders are assigned almost equally to two-thirds of the sample. Chi-square analyses revealed a relationship between diagnostic categories and subject variables of age and sex. These data suggest that boys, particularly between the ages of 6 and 13, are more frequently than girls categorized as Behavior Disorder, and that the Transient Situational Disorder category is overutilized for adolescents, both male and female.

Adolescent↗

PubMed2026

Genomic determinants of fluoroquinolone resistance in Escherichia coli in Nigeria: dominance of QRDR mutations and limited contribution of PMQR in a cross-sectional study.

BACKGROUND: Fluoroquinolone-resistant Escherichia coli is a major global clinical threat, particularly in low- and middle-income countries like Nigeria. However, the full genomic landscape, including the relative contributions of chromosomal mutations, plasmid-mediated resistance, and the role of high-risk clones, remains poorly characterized in this setting. This study aimed to define the genomic mechanisms, clonal distribution, and genotype-phenotype relationships of fluoroquinolone resistance in clinical E. coli isolates from Nigeria. METHODS: A cross-sectional study of 107 clinical E. coli isolates was conducted. Phenotypic susceptibility to ciprofloxacin and nalidixic acid was determined using VITEK 2 and broth microdilution. Whole-genome sequencing was performed, and analysis included detection of quinolone resistance determining region (QRDR) mutations (gyrA, parC, parE) and plasmid-mediated quinolone resistance (PMQR) genes, multilocus sequence typing (MLST), and phylogenetic analysis. Statistical associations were evaluated using chi-squared tests or Fisher's exact tests. RESULTS: Ciprofloxacin non-susceptibility was high at 86.0%. Resistance was primarily driven by a conserved chromosomal mutation profile; the combination of gyrA S83L, gyrA D87N, and parC S80I was present in 85 isolates and was associated with ciprofloxacin non-susceptibility in all affected isolates in this cohort. Isolates with only gyrA mutations were resistant to nalidixic acid but susceptible to ciprofloxacin, consistent with a stepwise resistance pathway. In this cohort, the triple QRDR signature (gyrA S83L + gyrA D87N/Y + parC S80I) was a perfect positive predictor of ciprofloxacin non-susceptibility (85/85; 100%). The ST131 lineage dominated, accounting for 21.5% of isolates and universally carrying the complete triple QRDR profile; notably, no ST131 isolate carried a PMQR determinant. Plasmid-mediated quinolone resistance (PMQR) genes were detected in 15.0% of isolates but were not independently associated with ciprofloxacin non-susceptibility in this cohort in the absence of concomitant QRDR mutations. Efflux pump genes were ubiquitous and non-predictive. Notably, six isolates, all from urine, were non-susceptible (R/I) despite lacking all known QRDR and PMQR determinants, pointing to uncharacterized mechanisms. In a multivariable logistic regression model that included ST131 status, PMQR carriage, and parE mutation status, ST131 was associated with ciprofloxacin non-susceptibility (adjusted OR 5.96, 95% CI 1.21-29.4, p = 0.028), whereas PMQR carriage was not (adjusted OR 0.94, 95% CI 0.18-4.85, p = 0.94). The triple QRDR signature was not included in this model because it perfectly predicted ciprofloxacin non-susceptibility in this cohort. Resistance patterns varied by clinical source, with the highest burden in bloodstream and wound infections. This stepwise hierarchy from first-step gyrA mutations to the classic triple QRDR profile is summarised in the graphical abstract, Fig. 1. CONCLUSIONS: Fluoroquinolone resistance in Nigerian clinical E. coli is predominantly driven by chromosomal QRDR mutations within successful clones like ST131. PMQR genes and efflux pumps appeared to play a supplementary role rather than being independent drivers of ciprofloxacin resistance in this cohort. These data support prioritising key QRDR mutations in genomic reporting and local stewardship decisions, while the QRDR-negative resistant urine isolates require further investigation.

Escherichia coli↗

PubMed1977

A survey of attitudes toward two motivating factors.

A survey was conducted to determine the attitudes clinical laboratory workers in Utah had toward two intrinsic aspects of work, challenge or appeal of work and self-fulfillment. Questionnaires were distributed to all major hospitals in Utah. Frequency distributions were obtained and Chisquare tests were performed to determine if significant differences existed in relationship to demographic variables. Respondents indicated that work was interesting, challenging, required thinking, and enabled them to make good use of past training, skills, and abilities. Findings showed they also responded positively to statements involving ample responsibility given for the position held, contribution to patient care, enjoyment of work, and feeling of self-importance. Negative attitudes were noted toward statements dealing with advancement in medical technology, adequate opportunities for continuing education at employer expense, and participation in decision making. The Chi-square test revealed workers in the hospitals surveyed differed significantly in their opinions about having adequate opportunities to attend workshops, etc., on employer time and expense, and also that personnel with varying educational levels felt significantly different about making suggestions concerning the laboratory.

Adult↗

PubMed2026

Genetic Correlation Between Brain Imaging Phenotypes and Externalizing Behavior: A Large-Scale LDSC Analysis of UK Biobank IDPs.

Externalizing has been associated with differences in brain structure and function; however, it remains unclear whether these associations reflect shared common-variant genetic influences. Cross-trait linkage disequilibrium score regression was used to estimate genome-wide genetic correlations between externalizing genome-wide association study (GWAS) results and 3,935 brain imaging-derived phenotypes from the UK Biobank BIG40 resource. The imaging phenotypes covered structural magnetic resonance imaging (MRI), diffusion MRI, susceptibility-weighted imaging, resting-state functional MRI, and task-based functional MRI. Results were included in the primary analysis when the imaging phenotype had positive single-nucleotide polymorphism (SNP) heritability, a heritability Z statistic of at least 1.96, a mean GWAS chi-square statistic of at least 1.02, at least 200,000 regression SNPs, and a complete LDSC result without a fatal error. Technical imaging quality-control phenotypes were excluded from biological inference. Individual results were corrected using the Benjamini-Hochberg false discovery rate procedure. Aggregated Cauchy association tests (ACATs) were used to evaluate evidence across all imaging phenotypes and within predefined imaging categories. Statistical power, simultaneous confidence bounds, and alternative quality-control definitions were examined in sensitivity analyses. Of the 3,935 imaging phenotypes, 3,716 produced estimable genetic correlations, 2,980 met the primary LDSC quality-control criteria, and 2,967 were classified as biological imaging phenotypes. No individual phenotype survived false discovery rate correction. The smallest unadjusted P value was 0.0005, and the minimum adjusted q value was 0.486. The distribution of genetic correlations was centered near zero, with a median genetic correlation of 0.0014 and a median absolute genetic correlation of 0.0338. ACAT provided no evidence of an aggregate association across all biological imaging phenotypes (P = 0.302), and no predefined imaging category survived multiple-testing correction. The median minimum detectable genetic correlation at 80% power was 0.216. Bonferroni-adjusted simultaneous confidence intervals were fully contained within the interval [-0.30, 0.30] for 80.0% of phenotypes in the primary analysis and 88.0% under the stringent heritability quality-control definition. Broad and stringent sensitivity analyses produced the same overall conclusions. In this study, no statistically robust evidence of genome-wide genetic correlations between externalizing and individual UK Biobank brain imaging phenotypes was found. Nevertheless, small, localized, mixed-direction, or developmentally specific genetic effects remain possible.

Journal Article↗

PubMed2026

Comparative Analysis of Potential Clinical Actionability of Genomic Alterations in Early-Onset Versus Later-Onset GI Cancers.

PURPOSE: As biomarker-directed therapy increasingly shapes GI oncology, it remains unclear whether early-onset (EO) and later-onset (LO) GI cancers harbor comparable opportunities for clinically actionable targeting. We compared the landscape of potentially actionable genomic alterations in EO versus LO GI cancers using American Association for Cancer Research Project Genomics Evidence Neoplasia Information Exchange v19.0. METHODS: GI tumor samples were assigned to 10 prespecified tumor groups using OncoTree codes. Samples were annotated with OncoKB therapeutic levels and classified as potentially actionable if they harbored at least one level 1-3B alteration. EO and LO disease were defined as age at sequencing <50 years and ≥50 years, respectively. Group-wise comparisons used Wilcoxon rank-sum, chi-square, or Fisher exact testing as appropriate and with false discovery rate correction. Multivariable logistic regression evaluated age group associations overall and within tumor groups. RESULTS: Among 53,945 GI tumor samples, 10,573 (19.6%) were EO and 43,372 (80.4%) were LO. EO tumors had lower prevalence of potentially actionable alterations in colorectal (71% v 78.1%, q < 0.001), esophagogastric (53.3% v 57.9%, q = 0.0097), GI stromal tumor (GIST) (75.1% v 90.9%, q < 0.001), liver (25.4% v 35.4%, q = 0.0021), and pancreatic tumors (82.9% v 90.7%, q < 0.001). In the overall model, LO status was associated with higher odds of potential actionability (odds ratio, 1.39 [95% CI, 1.33 to 1.47]; P < .001). Tumor group-specific associations persisted in colorectal, GIST, liver, and pancreatic tumors after multivariable adjustment. CONCLUSION: Potential clinical actionability differs between EO and LO GI cancers in a tumor lineage-specific manner. Several major EO GI tumor groups appear relatively depleted of potentially actionable alterations, suggesting that the expanding therapeutic reach of precision oncology may not be distributed evenly across age-defined GI cancer populations and underscoring the need for EO-focused biomarker discovery and therapeutic development.

Humans↗