# Postnatal determinants of testicular germ cell tumor by histological subtypes: The EPSAM1 and EPSAM2 studies

## TL;DR

This study finds that taller childhood and adult height, along with early hospitalizations, increase the risk of testicular germ cell tumors, mainly seminomas.

## Contribution

The study provides updated evidence on postnatal environmental factors influencing testicular germ cell tumor risk and highlights differences between seminomas and nonseminomas.

## Key findings

- Taller childhood and pubertal height are linked to increased testicular germ cell tumor risk.
- Exceeding genetically predicted adult height is associated with higher tumor risk.
- Hospitalizations in early life, especially for immune-related conditions, are linked to increased risk.

## Abstract

The EPSAM study is an ongoing case–control study evaluating the postnatal risk factors for testicular germ‐cell tumor (TGCT). We aimed at updating the risk estimates for factors identified in previous EPSAM analyses and studying heterogeneities between seminomas and non‐seminomas. TGCT cases (N = 358) and controls (N = 459) were recruited in two phases (EPSAM1, population‐based, and EPSAM2, hospital based). We analyzed the associations with TGCT the following characteristics: (i) anthropometrics at different ages; (ii) baldness; (iii) sibship size; (iv) physical activity at age 13 years; and (v) hospitalizations up to age 18 years. Odds Ratios (ORs) for TGCTs and Relative Risk Ratios (RRRs) for seminomas and non‐seminomas were estimated using unconditional and multinomial logistic regression models. We observed an increased risk of TGCT for height in childhood (OR: 1.83, 95% CI: 1.16–2.90, for taller vs. shorter than peers), pubertal height (OR: 1.40, 0.92–2.11, for taller vs. shorter than peers), adult height above the parental genetic target (OR: 1.47; 1.04–2.07), and any hospitalization in the first 18 years, in particular for diseases with an immune pathogenesis (OR 2.93, 1.33–6.44). Baldness, sibship size, and competitive sports at age 13 years were inversely associated with TGCT risk. Although all anthropometric characteristics were associated with seminomas and showed weaker or no associations with non‐seminomas, there was little evidence of heterogeneity between the two, except for adult height compared to target height. The updated results of the EPSAM study support the role of postnatal environmental factors in TGCT etiology, with an overall lack of heterogeneity between seminomas and nonseminomas.

What's new?

While several nongenetic risk factors are linked to testicular germ‐cell tumors (TGCTs), the influence of environmental and hormonal factors remains unclear. This study evaluated the role of postnatal exposures in the etiology of TGCT using data from the ongoing EPSAM case–control investigation in Italy. Analyses show that childhood and adolescent height, as well as exceeding one's genetically predicted height, increase TGCT risk. Associations were observed predominantly for seminomas. The findings reinforce the role of early‐life exposures in testicular carcinogenesis and suggest possibly distinct etiopathogenetic mechanisms for seminomas and nonseminomas, offering new insights for prevention strategies.