RESUMEN
Testicular germ cell tumors (TGCTs) are a clinically and pathologically heterogeneous disease, and little is known of its genetic basis. Only low susceptibility risk loci have been identified for both sporadic and familial cases. Therefore, we tried to identify new susceptibility genes responsible for familial testicular cancer that may contribute to increasing our knowledge about the genetic basis of the disease. Nineteen Spanish families with at least two affected individuals with TGCT were selected. WES was performed on those individuals using an Illumina Hiseq2000 sequencing platform. Data were analyzed under a monogenic and polygenic model of inheritance, and candidate variants were evaluated in a case-control association study performed on 391 Spanish sporadic cases and 1,170 healthy Spanish controls. Results were replicated in a second series consisting of 101 TGCTs from the Cancer Genome Atlas (TGCA) and 27,000 controls from the Exome Aggregation Consortium (ExAC) database. Logistic regression was carried out to analyze the association strength (risk) of candidate variants obtained among cases and controls in different populations. Despite the sample size, we detected a significant earlier age of onset in familial TGCT (28y) than sporadic cases (33y), using a Mann-Whitney U test. We identified significant variants in the comparative study of TGCT cases (391) versus controls (almost 1,170), and three of them [PLEC (OR = 6.28, p = 6.42 × 10-23 ) (p.Arg2016Trp), EXO5 (OR = 3.37, p = 4.82 × 10-09 ) (p.Arg344AlafsTer10) and DNAH7 (OR = 1.64, p = 0.048)] were replicated as potential candidates that may contribute to explaining the genetic basis of TGCT.
Asunto(s)
Dineínas Axonemales/genética , Exonucleasas/genética , Predisposición Genética a la Enfermedad/genética , Plectina/genética , Neoplasias Testiculares/genética , Adolescente , Adulto , Anciano , Estudios de Casos y Controles , Niño , Preescolar , Exoma/genética , Femenino , Herencia/genética , Humanos , Lactante , Masculino , Persona de Mediana Edad , Linaje , Factores de Riesgo , Secuenciación del Exoma/métodos , Adulto JovenRESUMEN
BACKGROUND: Gender composition among surgical academic leadership, including academic medical journals, disproportionately favors men and may inadvertently introduce a bias. An understanding of the factors associated with gender representation among urologic journals may aid in prioritizing an equitable balance. OBJECTIVE: To evaluate female representation on editorial boards of pre-eminent international urologic journals. DESIGN, SETTING, AND PARTICIPANTS: The names and position descriptions of urologic journal leadership appointees were collected in October 2021. Gender was assessed using gender-api.com or through personal title, as available. Journal characteristics were summarized using SCImago, a bibliometric indicator database extracted from Scopus journal data. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: A multivariate logistic regression analysis was performed to describe associations between SCImago Journal Rank (SJR) quartile and geographic region with female gender representation. Quartile 1 (Q1) was considered the top quartile and Q4 the bottom quartile concordant with journal impact factor. RESULTS AND LIMITATIONS: A total of 105 urology-focused journals were identified with 5989 total editorial board members, including 877 (14.6%) female, 5112 (85.4%) male, and two nonbinary persons. Female representation differed significantly by journal leadership position, SJR quartile, and geographic region. On the multivariate analysis of overall female representation, Q1 journals had higher odds of female representation than Q2 and Q3 journals, and had no significant difference from Q4 journals. Additionally, compared with Western Europe, North American journals had 78% higher odds while Asiatic journals had 50% lower odds of female representation. This study is limited by the inability to account for outside factors that lead to invitation or acceptance of journal leadership positions. CONCLUSIONS: Contemporary female leadership at urology journals is about six times less common than male leadership across all journals, although trends in their proportion were noted when assessed by journal quartile and region. Addressing this gender imbalance represents an important step toward achieving gender equity in the field of urology. PATIENT SUMMARY: In this study, we looked at the gender balance of academic journal leaders who serve as gatekeepers for sharing urologic research with the public. We found that the most prestigious journals and those in western countries tended to have the highest female representation. We hope that these findings help the academic community recognize and improve gender representation.