Characteristics of a single-centre series of familial testicular germ cell tumours

Abstract

10039 Background: Testicular germ cell tumors (TGCTs) account for 1% of all male cancers with increasing incidence rates documented. A family history of TGCT occurs in 2% of patients, conferring relative risks of 8–10 for brothers and 4–6 for fathers or sons of patients. These risks are high in comparison to other solid cancers and suggest that the risk of developing TGCT may be, at least in part, inherited rather than acquired. Methods: Pedigrees with >1 male family member with TGCT were identified from a tumor database and systematically collected from 1992. Patients donated samples and medical details with full informed consent and under ethical review board approval. Pedigree and medical data were obtained by interview, mail and telephone contact. Results: This series examines 78 pedigrees, containing 160 cases and 170 TGCTs. In the period 1994–2003 6% of all cases had a family history of TGCT. It includes 35 sib-pairs, 12 father-son pairs, 11 uncle-nephew pairs, 10 cousin pairs and 4 pedigrees with ≥ 3 cases of TGCT. The dataset contains 66 seminomas, 56 non-seminomas, 17 mixed histology, 1 CIS and 30 tumors of unconfirmed histology. The median age at diagnosis was 33 (range 17 to 87). The median difference in age at diagnosis between the cases in each pedigree was 6 years (0–58). Histology was concordant between family members in 22 of the 53 (41.5%) 2-case pedigrees. 11 pedigrees contained a case with bilateral TGCTs (6.9% of all cases, compared to 1.1% in the sporadic patient population, p<0.001) with 50% histological concordance. The median age at diagnosis of bilateral tumors was 32 (21–42) for the first tumor and 35 (26–49) for second tumors. 24 TGCT cases (15%, compared to an expected rate of 10%, p=0.045) reported a history of UDT. 9/162 (5.5%) of TGCT cases also developed non-TGCT cancers, including penile, bladder, colorectal, hepatic and pancreatic tumors. Conclusions: When systematic collection is undertaken the incidence of familial TGCT may be higher than previously reported. Familial cases have a higher incidence of UDT and bilateral disease. The majority of this set has been used in an international genome-wide linkage analysis to identify TGCT susceptibility genes. No significant financial relationships to disclose.