Risk of germ cell tumors among men with HIV/acquired immunodeficiency syndrome
ABSTRACT Men with HIV/acquired immunodeficiency syndrome (AIDS) are reported to be at increased risk for germ cell tumors (GCT), particularly testicular seminoma. We investigated correlates of this association to improve understanding of GCTs.
Testicular and extratesticular seminoma and nonseminoma cases were found by linking population-based cancer and HIV/AIDS registry data for 268,950 men who developed AIDS in 1980 to 2003. Standardized incidence ratios (SIR) with 95% confidence intervals (95% CI) were used to compare these cases with the number of cases expected in the demographically matched population.
Overall, seminoma risk (161 cases: SIR, 1.9; 95% CI, 1.6-2.2) was increased significantly with HIV/AIDS, whereas nonseminoma risk was not (56 cases: SIR, 1.3; 95% CI, 0.96-1.7). Extratesticular GCT risk also was increased (11 cases: SIR, 2.1; 95% CI, 1.1-3.7). Seminoma risk was elevated regardless of age, race, or HIV/AIDS transmission group. It was highest for disseminated disease (SIR, 4.7; 95% CI, 2.9-7.2) and within 9 months of AIDS onset (SIR, 7.6; 95% CI, 5.8-9.6), but it was unrelated to CD4 count and duration of HIV/AIDS. The excess risk of seminoma declined in more recent calendar periods, and it was no longer elevated (SIR, 1.4; 95% CI, 0.9-1.9) in the highly active antiretroviral treatment era.
Men with HIV/AIDS had an increased risk of seminoma, but this risk may have attenuated with improving anti-HIV/AIDS treatments. Although detection bias could partly explain the excess of this cancer, various lines of evidence support a causal relationship. Possible mechanisms underlying this association include impaired tumor immunosurveillance or AIDS-related testicular atrophy.
- SourceAvailable from: Martin Rijlaarsdam
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- "The progression of CIS to invasive TGCC is not yet completely understood, although the loss of PTEN has been shown to be a common event . Even though a role of the immune system in TGCC pathogenesis has been suggested  , studies regarding the specificity and the effect of immune response upon invasion contradict each other  . With regard to their genomic constitution upon malignant transformation, polyploidization to a tetraploid stage is thought to be an early event, occurring before the formation of CIS  . "
ABSTRACT: Germ cell tumors (GCTs) represent a diverse group of tumors presumably originating from (early fetal) developing germ cells. Most frequent are the testicular germ cell cancers (TGCC). Overall, TGCC is the most frequent malignancy in Caucasian males (20-40yr) and remains an important cause of (treatment related) mortality in these young men. The strong association between the phenotype of TGCC stem cell components and their totipotent ancestor (fetal primordial germ cell or gonocyte) makes these tumors highly relevant from an onco-fetal point of view. This review subsequently discusses the evidence for the early embryonic origin of TGCCs, followed by an overview of the crucial association between TGCC pathogenesis, genetics, environmental exposure and the (fetal) testicular micro-environment (genvironment). This culminates in an evaluation of three genvironmentally modulated hallmarks of TGCC directly related to the oncofetal pathogenesis of TGCC: (1) maintenance of pluripotency, (2) cell cycle control/cisplatin sensitivity and (3) regulation of proliferation/migration/apoptosis by KIT-KITL mediated receptor tyrosine kinase signaling. Briefly, TGCC exhibit identifiable stem cell components (seminoma and embryonal carcinoma) and progenitors that show large and consistent similarities to primordial/embryonic germ cells, their presumed totipotent cells of origin. TGCC pathogenesis depends crucially on a complex interaction of genetic and (micro-)environmental, i.e. genvironmental risk factors that have only been partly elucidated despite significant effort. TGCC stem cell components also show a high degree of similarity with embryonic stem/germ cells (ES) in the regulation of pluripotency and cell cycle control, directly related to their exquisite sensitivity to DNA damaging agents (e.g. cisplatin). Of note, (ES specific) micro-RNAs play a pivotal role in the crossover between cell cycle control, pluripotency and chemosensitivity. Moreover, multiple consistent observations reported TGCC to be associated with KIT-KITL mediated receptor tyrosine kinase signaling, a pathway crucially implicated in proliferation, migration and survival during embryogenesis including germ cell development. In conclusion, TGCCs are a fascinating model for onco-fetal developmental processes especially with regard to studying cell cycle control, pluripotency maintenance and KIT-KITL signaling. The knowledge presented here contributes to better understanding of the molecular characteristics of TGCC pathogenesis, translating to identification of at risk individuals and enhanced quality of care for TGCC patients (diagnosis, treatment and follow-up).Seminars in Cancer Biology 07/2014; 29. DOI:10.1016/j.semcancer.2014.07.003 · 9.33 Impact Factor
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ABSTRACT: Malignancy occurs with increased frequency in the HIV-positive population. The true incidence of prostate cancer in this population is unknown. In the few cases that have been presented in the literature, prostate cancer in HIV-positive men appears to behave much like it does in HIV-negative men. Prostate cancer is the most common malignancy in men and the second leading cause of cancer death. Approximately 800,000 men in the United States are HIV positive, and innovative therapies have dramatically improved survival. HIV disproportionately impacts ethnic groups with increased risk of prostate cancer and has been associated with increases in the incidence of certain malignancies. Despite the high prevalence of both diseases, there is relatively little literature about prostate cancer in HIV-positive patients. There is no consensus on how to screen or treat this patient population. We review the literature with regards to incidence, screening, treatment, and outcomes of this poorly characterized population. We briefly discuss the impact of highly active antiretroviral therapy and testosterone supplementation in the development of prostate cancer. A systematic review of the literature was conducted using MEDLINE key words 'HIV,' 'prostate,' 'prostate cancer' and 'AIDS.' Manual bibliographic review of cross-referenced items was also performed. A total of 176 unique abstracts and publications were reviewed; many authors provided data on the incidence of HIV and various malignancies including prostate cancer. Twelve unique publications providing detailed information on 60 patients with HIV and prostate cancer were identified. Prostate cancer is a common malignancy in HIV-positive men. With improved therapies for HIV and increasing survival, the importance for screening and treating prostate cancer is increasing. Acute outcomes of treatment do not demonstrate increased acute morbidity; however long-term outcomes have not been reported.Prostate cancer and prostatic diseases 09/2008; 12(1):6-12. DOI:10.1038/pcan.2008.44 · 2.83 Impact Factor