Asociaciones entre la distancia anogenital, la razón digital 2D:4D y el cáncer de testículo

Abstract

Introduction: in the last two decades a large number of studies have analysed testicular germ cells tumours (TGCT) because of their incidence in young men and their impact in sexual function, quality of life and the risk of adverse events. Nowadays TGCT is considered as a model for a curable cancer, it resides in being diagnosed in an early stage and a multidisciplinary treatment approach. The development of TGCT have been established to start at very early stage and different factors have been reported as causative factors in this period, such as disruptions in sexual hormonal environment. Anogenital distance (AGD) and the ratio of second to fourth digit lengths (2D: 4D ratio) are proposed biomarkers for prenatal sex hormones environment and sexually dimorphic phenotypes, which could be measure in adulthood. The aim of our study is to analyse the relationship between those biomarkers and the risk of develop a TGCT. Material and Methods: unmatched case-control study was conducted between May 2013 and September 2019 at the Department of Urology of the University Hospital Reina Sofía in Murcia (South-eastern Spain). Cases (n=42) were men attending at this hospital and all of them underwent radical orchiectomy and were diagnosed by specimen's histopathology. Controls (n=54) were men randomly selected from the outpatient's list of the same hospital department. These patients were adult men who showed no signs or symptoms of malignant testicular disease or other entity related to Testicular Dysgenesis Syndrome. Body weight (kilograms) and height (meters) were measured, and different scrotal abnormalities were evaluated. Each examiner measured, without known the condition of case or control, 2D: 4D ratio from the right hand twice each one, with a method of direct measurements. Two types of AGD, anus-penis (AGDAP) and anus-scrotum (AGDAS), were measured in lithotomy position three times each one. Both lengths were measured using a digital calliper (Stainless Steel Digital Calliper, VWR¿ International, LLC, West Chester, PA, USA). Average values of the different measurements were used in the statistical analyses. Continuous variables were compared using Kolmogorov-Smirnov test and categorical variables with Chi-squared test. Unconditional multiple logistic regression was performed to explore the association between presence of TGCT and 2D: 4D ratio in tertiles in one side, and TGCT and both types of AGD in tertiles in other side; with the highest tertile as reference category using odds ratios (OR) and 95% confidence intervals (CI). The age and BMI (kg/m2) were used as covariates in the adjusted models. All tests were two-tailed at 0.05 significance level. Analyses were carried out with IBM SPSS 20.0 (IBM Corporation, Armonk, New York, USA). Results: for the entire population cases were older than controls but not significantly differences were found in BMI. Based on tumour histology cases were divided into seminoma (42,9%) and non-seminoma (57,1%). Among cases, nobody had history of cryptorchidism or hypospadias. Both groups showed similar values of 2D: 4D ratio and AGD measurements, no significant differences were found between testicular cancer cases and healthy men. No statistical relationship was found between 2D: 4D ratio, AGD and the presence of testicular cancer in crude or adjusted models. Taking the third tertile of 2D:4D ratio and AGD as a reference, our results did not report bigger 2D: 4D ratio neither AGD as risk factors of suffer a testicular cancer. Conclusions: our results could not allow establishing a relationship between TCGT, AGD and 2D: 4D ratio. Nevertheless, the knowledge about the association of AGD and 2D: 4D ratio with sexual hormonal environment in fetal period and an embryological origin boost us to continue analysing the different agents which take part in the physiopathology process of TGCT.