(102) HYPOGONADISM AND CANCER INCIDENCE IN MEN WITH KLINEFELTER SYNDROME: A POPULATION-LEVEL ANALYSIS
Authors: Asanad K , Horns J , Samplaski M , Hotaling J 
Published: December 2024

Abstract

Introduction
Men with Klinefelter syndrome (KS) have an increased risk of certain malignancies such as breast cancer, lymphoma, and extragonadal germ cell tumors. To our knowledge, this has not been evaluated using a population-level analysis nor has the impact of hypogonadism on cancer risk in men with KS been ascertained.

Objective
We sought to investigate the incidence of various malignancies such as lung cancer, breast cancer, prostate cancer, testicular cancer (ie, germ cell tumors and extragonadal germ cell tumors), and lymphoma (Hodgkin and non-Hodgkin) in men with KS compared to men in the general population using a population-based assessment. We also aimed to understand the impact of hypogonadism on cancer risk in men with KS.

Methods
We used the Merative MarketScan database of commercial claims encounters to identify all men diagnosed with KS and matched each to a non-KS control based on age. Men were followed throughout their enrollment and evaluated for the various cancer diagnoses, excluding those with metastasis to the primary organ of interest as well as familial genetic predisposition. Univariable analysis using Kruskal-Wallis tests (for continuous variables) and Chi-squared tests (for categorical and binary variables) of demographic and comorbid variables stratified by KS diagnosis was performed. Multivariate logistic regression analysis was used to identify predictors of cancer diagnosis occurrence (of any type) controlling for age in men with KS.

Results
We identified a final cohort of 13 326 men, of which 50% were diagnosed with KS (6663 cases and 6663 controls) during the study period. The average age of men in the cohort was 25 years (range 15–40). Hypogonadism was significantly more common in men with KS compared to controls (32.1% vs. 1.1%, p &lt; 0.001). Compared to controls, men with KS had a significantly higher incidence of Hodgkin lymphoma (0.15% vs. 0%, p = 0.004), non-Hodgkin lymphoma (0.17% vs. 0%, p = 0.003), lung cancer (0.23% vs 0.06%, p = 0.022), breast cancer (0.23% vs. 0.06%, p = 0.022), and extragonadal germ cell tumors (0.23% vs. 0.06%, p = 0.022). In contrast, compared to controls, men with KS had a significantly lower incidence of prostate cancer (0.24% vs. 0.57%, p = 0.004) and testicular germ cell tumors (0.24% vs. 0.57%, p = 0.004). On multivariable logistic regression, increasing age in men with KS was significantly associated with an increased cancer risk (OR 1.09, 95% CI 1.07-1.11, p &lt; 0.001), while hypogonadism was significantly associated with a decreased cancer risk (OR 0.47, 95% CI 0.25-0.85, p = 0.014) (Table 1).

Conclusions
This is the first population-level analysis to identify that men with KS have a significantly increased incidence of lung cancer, breast cancer, lymphoma (Hodgkin and non-Hodgkin), and extragonadal germ cell tumors, but a significantly decreased incidence of prostate cancer and testicular germ cell tumors. Hypogonadal men with KS have approximately 50% decreased odds of developing cancer. Further research is needed to better understand the relationship between testosterone deficiency and KS on the risk of malignancy.

Disclosure
No.