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Tumor mutational burden (TMB) is a potential biomarker associated with response to immune checkpoint inhibitor therapies. The prognostic value associated with TMB in the absence of immunotherapy is uncertain.

To assess the prevalence of high TMB (TMB-H) and its association with overall survival (OS) among patients not treated with immunotherapy with the same 10 tumor types from the KEYNOTE-158 study.

This retrospective cohort study evaluated the prognostic value of TMB-H, assessed by Foundation Medicine (FMI) and defined as at least 10 mutations/megabase (mut/Mb) in the absence of immunotherapy. this website Data were sourced from the deidentified Flatiron Health-FMI clinicogenomic database collected up to July 31, 2018. Eligible patients were aged 18 years or older with any of the following solid cancer types anal, biliary, endometrial, cervical, vulvar, small cell lung, thyroid, salivary gland, mesothelioma, or neuroendocrine tumor. Patients with microsatellite instability-high tumors were excluded from primary anth TMB-H vs those without TMB-H was 0.94 (95% CI, 0.77-1.13). Comparable results were observed when including patients with high microsatellite instability tumors and calculating OS from first observed antineoplastic treatment date.

These findings suggest that prevalence of TMB-H varies widely depending on tumor type and TMB-H does not appear to be a factor associated with OS among patients across these cancer types treated in the absence of immunotherapy.

These findings suggest that prevalence of TMB-H varies widely depending on tumor type and TMB-H does not appear to be a factor associated with OS among patients across these cancer types treated in the absence of immunotherapy.

Understanding the genetic contribution of the major histocompatibility complex (MHC) region to the risk of cervical cancer (CC) will help understand how immune responses to infection with human papillomaviruses are associated with CC.

To determine whether the HLA-B*5201 allele is associated with CC in Japanese women.

This was a multicenter genetic association study. Genotype and phenotype data were obtained from BioBank Japan Project. Additional patients with CC were enrolled from the Aichi Cancer Center Research Institute. An MHC fine-mapping study was conducted on CC risk in the Japanese population by applying a human leukocyte antigen (HLA) imputation method to the large-scale CC genome-wide association study data of using the Japanese population-specific HLA reference panel. Participants included 540 women in BioBank Japan Project with CC or 39 829 women without gynecologic diseases, malignant neoplasms, and MHC-related diseases as controls. An additional 168 patients with CC were recruited from AicHLA alleles remained significant after conditioning on the HLA-B*5201. The HLA amino acid residue-based analysis suggested that HLA-B p.Tyr171His located in the peptide-binding groove was associated with the most significant CC risk (odds ratio, 1.47; 95% CI, 1.30-1.66; P = 1.2 × 10-9).

The results of this study contribute to understanding of the genetic background of CC. The results suggest that immune responses mediated by class I HLA molecules are associated with susceptibility to CC.

The results of this study contribute to understanding of the genetic background of CC. The results suggest that immune responses mediated by class I HLA molecules are associated with susceptibility to CC.

Obesity is a global health challenge and a risk factor for atherosclerotic cardiovascular disease (ASVCD). Performance of the pooled cohort equations (PCE) for ASCVD risk by body mass index (BMI; calculated as weight in kilograms divided by height in meters squared) is unknown.

To assess performance of the PCE across clinical BMI categories.

This cohort study used pooled individual-level data from 8 community-based, prospective, longitudinal cohort studies with 10-year ASCVD event follow-up from 1996 to 2016. We included all adults ages 40 to 79 years without baseline ASCVD or statin use, resulting in a sample size of 37 311 participants. Data were analyzed from August 2017 to July 2020.

Participant BMI category underweight (<18.5), normal weight (18.5 to <25), overweight (25 to <30), mild obesity (30 to <35), and moderate to severe obesity (≥35).

Discrimination (Harrell C statistic) and calibration (Nam-D'Agostino χ2 goodness-of-fit test) of the PCE across BMI categories. Improvement inegories, particularly individuals with high estimated risk. Incorporation of the usual clinical measures of obesity did not improve risk estimation of the PCE. Future research is needed to determine whether incorporation of alternative high-risk obesity markers (eg, weight trajectory or measures of visceral or ectopic fat) into the PCE may improve risk prediction.

These findings suggest that the PCE had acceptable model discrimination and were well calibrated at clinical decision thresholds but overestimated risk of ASCVD for individuals in overweight and obese categories, particularly individuals with high estimated risk. Incorporation of the usual clinical measures of obesity did not improve risk estimation of the PCE. Future research is needed to determine whether incorporation of alternative high-risk obesity markers (eg, weight trajectory or measures of visceral or ectopic fat) into the PCE may improve risk prediction.

Children with birth defects have a greater risk of developing cancer, but this association has not yet been evaluated in children conceived with in vitro fertilization (IVF).

To assess whether the association between birth defects and cancer is greater in children conceived via IVF compared with children conceived naturally.

This cohort study of live births, birth defects, and cancer from Massachusetts, New York, North Carolina, and Texas included 1 000 639 children born to fertile women and 52 776 children conceived via IVF (using autologous oocytes and fresh embryos) during 2004-2016 in Massachusetts and North Carolina, 2004-2015 in New York, and 2004-2013 in Texas. Children were followed up for an average of 5.7 years (6 008 985 total person-years of exposure). Data analysis was conducted from April 1 to August 31, 2020.

Conception by IVF for state residents who gave birth to liveborn singletons during the study period. Birth defect diagnoses recorded by statewide registries.

Cancer diagnosis as recorded by state cancer registries.