Identification of four autophagy-related genetic variants as risk factors for chronic lymphocytic leukemia.

We investigated the influence of 55,583 autophagy-related single nucleotide polymorphisms (SNPs) on chronic lymphocytic leukemia (CLL) risk across four independent populations comprising 5,472 CLL cases and 726,465 controls. We also examined their impact on overall survival (OS), time to first treatment (TTFT), autophagy flux, and immune responses. A meta-analysis of the four populations identified, for the first time, significant associations between CDKN2A (rs3731204) and BCL2 (rs4940571, rs12457371, rs1026825) SNPs and CLL risk, with CDKN2A showing the strongest association (p=1.

A randomized trial to evaluate the impact of breast density notification on anxiety, breast cancer worry, and perceived risk among Latinas at a federally qualified health center : Breast density notification and anxiety, breast cancer worry, and perceived risk among Latinas.

Background: Laws mandating that women be informed of mammographic breast density (MBD) with their mammogram results may increase anxiety. We report on changes in self-reported levels of anxiety, worry about developing breast cancer (BC), as well as perceived risk of BC resulting from three MBD notification methods: usual care (mailed notification letter), enhanced care (usual care with MBD educational brochure), or interpersonal care (enhanced care with promotora education), among a Latina population.

Methods: A randomized controlled clinical trial of three MBD notifications was performed among Latina women aged 40 to 74 years receiving screening mammography at a federally qualified health center (FQHC).

Radiomic Parenchymal Phenotypes of Breast Texture from Mammography and Association with Risk of Breast Cancer.

Background Parenchymal phenotypes reflect the intrinsic heterogeneity of both tissue structure and distribution on mammograms. Purpose To define parenchymal phenotypes on the basis of radiomic texture features derived from full-field digital mammography (FFDM) in breast screening populations and assess associations of parenchymal phenotypes with future risk of breast cancer and masking (false-negative [FN] findings or interval cancers), beyond breast density, and by race and ethnicity Materials and Methods A two-stage study design included a retrospective cross-sectional study of 30 000 randomly selected women with four-view FFDM (mean age, 57.4 years) and a nested case-control study of 1055 women with invasive breast cancer (151 Black and 893 White women) matched to 2764 women without breast cancer (411 Black and 2345 White women) (mean age, 60.

Risk of lymphoid malignancy associated with cancer predisposition genes.

We investigated the prevalence of rare inherited pathogenic variants (PV) in 19 cancer predisposition genes regularly included on multi-gene panel testing based on NCCN guidelines and their association with the risk of lymphoid malignancies (LM) overall and by common lymphoma subtypes and multiple myeloma. The study population included newly diagnosed LM cases (N = 6990) and unrelated controls (N = 42,632), excluding individuals with a history of hematologic malignancy. Whole exome sequencing was performed on DNA from whole blood.

Effectiveness of Breast Density Educational Interventions on Mammography Screening Adherence Among Underserved Latinas: A Randomized Controlled Trial.

Latinas with mammographic dense breasts are at increased risk of breast cancer. This randomized controlled trial tests the effectiveness of three breast density (BD) educational approaches on adherence to subsequent mammography screening among Latinas receiving care at a Federally Qualified Health Center (FQHC). Adherence was ascertained using electronic health record and survey responses.

Risk of Incident Melanoma Among Individuals With Low-Count Monoclonal B-Cell Lymphocytosis.

Purpose: Chronic lymphocytic leukemia (CLL)-phenotype monoclonal B-cell lymphocytosis (MBL) is a premalignant condition that is roughly 500-fold more common than CLL. It is unknown whether the two-fold increased risk of developing melanoma associated with CLL extends to individuals with MBL.

Methods: Using the Mayo Clinic Biobank, we identified participants who were 40 years or older with no previous hematological malignancies, who resided in the 27 counties around Mayo Clinic, and who had available biospecimens for screening.

The Importance of Estimating Excess Deaths Regionally During the COVID-19 Pandemic.

National or statewide estimates of excess deaths have limited value to understanding the impact of the COVID-19 pandemic regionally. We assessed excess deaths in a 9-county geographically defined population that had low rates of COVID-19 and widescale availability of testing early in the pandemic, well-annotated clinical data, and coverage by 2 medical examiner's offices. We compared mortality rates (MRs) per 100,000 person-years in 2020 and 2021 with those in the 2019 reference period and MR ratios (MRRs).

Tumor mutational load is prognostic for progression to therapy among high-count monoclonal B-cell lymphocytosis.

High-count monoclonal B-cell lymphocytosis (HCMBL) is a precursor condition to chronic lymphocytic leukemia (CLL). We have shown that among individuals with HCMBL, the CLL-International Prognostic Index (CLL-IPI) is prognostic for time-to-first therapy (TTFT). Little is known about the prognostic impact of somatically mutated genes among individuals with HCMBL.

Polymorphisms within Autophagy-Related Genes as Susceptibility Biomarkers for Multiple Myeloma: A Meta-Analysis of Three Large Cohorts and Functional Characterization.

Multiple myeloma (MM) arises following malignant proliferation of plasma cells in the bone marrow, that secrete high amounts of specific monoclonal immunoglobulins or light chains, resulting in the massive production of unfolded or misfolded proteins. Autophagy can have a dual role in tumorigenesis, by eliminating these abnormal proteins to avoid cancer development, but also ensuring MM cell survival and promoting resistance to treatments. To date no studies have determined the impact of genetic variation in autophagy-related genes on MM risk.

A pleiotropic variant in DNAJB4 is associated with multiple myeloma risk.

Pleiotropy, which consists of a single gene or allelic variant affecting multiple unrelated traits, is common across cancers, with evidence for genome-wide significant loci shared across cancer and noncancer traits. This feature is particularly relevant in multiple myeloma (MM) because several susceptibility loci that have been identified to date are pleiotropic. Therefore, the aim of this study was to identify novel pleiotropic variants involved in MM risk using 28 684 independent single nucleotide polymorphisms (SNPs) from GWAS Catalog that reached a significant association (P < 5 × 10 ) with their respective trait.

Does a Multiple Myeloma Polygenic Risk Score Predict Overall Survival of Patients with Myeloma?

Background: Genome-wide association studies (GWAS) of multiple myeloma in populations of European ancestry (EA) identified and confirmed 24 susceptibility loci. For other cancers (e.g.

Body mass index associated with monoclonal gammopathy of undetermined significance (MGUS) progression in Olmsted County, Minnesota.

Monoclonal gammopathy of undetermined significance (MGUS) is a premalignant clonal disorder that progresses to multiple myeloma (MM), or other plasma-cell or lymphoid disorders at a rate of 1%/year. We evaluate the contribution of body mass index (BMI) to MGUS progression beyond established clinical factors in a population-based study. We identified 594 MGUS through a population-based screening study in Olmsted County, Minnesota, between 1995 and 2003.

Prevalence of heavy chain MGUS by race and family history risk groups using a high-sensitivity screening method.

Mass-spectrometry (MS) assays detect lower levels of monoclonal proteins and result in earlier detection of monoclonal gammopathy of undetermined significance (MGUS). We examined heavy chain MGUS prevalence using matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) MS among 3 risk groups, ages 50 or older: 327 African Americans (AA) and 1223 European Americans (EA) from a clinical biobank and 1093 unaffected first-degree relatives (FDR) of patients with hematologic disorders. Age- and sex-adjusted prevalence rates were directly standardized to 2010 United States population.

Association of EDARV370A with breast density and metabolic syndrome in Latinos.

The ectodysplasin receptor (EDAR) is a tumor necrosis factor receptor (TNF) superfamily member. A substitution in an exon of EDAR at position 370 (EDARV370A) creates a gain of function mutant present at high frequencies in Asian and Indigenous American populations but absent in others. Its frequency is intermediate in populations of Mexican ancestry.