Familial testicular cancer: a report of the UK family register, estimation of risk and an HLA class 1 sib-pair analysis

Abstract

(1985), using data derived from a study of 225 men with testicular cancer, calculated that having a first degree relative with testicular cancer was associated with a 6-fold elevated risk in comparison with the general population. There has been relatively little research into whether the excess in familial cases occurs as a result of a genetic predisposition, common environment or both (Gedde-Dahl et al., 1985;Dieckmann et al., 1987;Forman, 1989;Oliver, 1990).We have established a UK-based register for familial testicular cancer to provide a means for the systematic documentation of new cases, including histological verification, and for obtaining standardised lymphocyte-DNA samples from affected and unaffected family members for subsequent genetic linkage analysis. In this paper we describe data on the first 42 families reported to the register for which confirmation of the diagnosis has been obtained.A sub-set of these families were identified from interviews about family history with men diagnosed as having testicular cancer for whom an age-matched control was also interviewed. Using these families, it was possible to estimate the

Familial testicular cancer in Norway and southern Sweden

“…Taken together with data from the literature (Forman et al, 1992;Tollerud et al, 1985), this suggests that the risk from being related to a TC patient is not dependent on the risk conferred by UDT.…”

“…It seems unlikely that there are separate risk factors in the two countries restricting the excess risk in Swedes to first-degree relatives, and we believe the discrepancy may be due to underreporting of cases in distant relatives in Sweden. Forman et al (1992) in TC patients from the UK when excluding the older generation to correct for ascertainment bias. In the present data set we found the age difference to be present only in seminomas.…”

“…Two reports have estimated the relative risk to first-degree relatives of TC cases to be between 6 and 10 (Tollerud et al., 1985;Forman et al, 1992). This estimate is considerably higher than that for most common cancers in which it rarely exceeds 4 (Forman et al, 1992). The proportion of TC that is familial is, however, considered to be very low (0.2-2.2% of cases) (Dieckmann et al, 1987).…”

Testicular microlithiasis as a familial risk factor for testicular germ cell tumour

“…Risk factors for TGCT include a family history of disease (Forman et al, 1992;Westergaard et al, 1996;Heimdal et al, 1996a;Sonneveld et al, 1999;Hemminki and Li, 2004), a previously diagnosed germ cell tumour (Osterlind et al, 1991;Wanderas et al, 1997), a history of undescended testis (Brown et al, 1987;Swerdlow et al, 1997), infertility (Petersen et al, 1998;Moller and Skakkebaek, 1999;Jacobsen et al, 2001;Richiardi et al, 2004), atrophy (Harland et al, 1998), and gonadal dysgenesis (Verp and Simpson, 1987). In a proportion of cases (B2%), a first-degree family member is also affected with the disease (Forman et al, 1992). The relative risk to a brother of a TGCT case is 8 -10 (Forman et al, 1992;Heimdal et al, 1996b;Hemminki and Li, 2004), which is higher than for most other cancer types that rarely exceed four (Dong and Hemminki, 2001) and suggests that predisposition genes are important in this disease.…”

Somatic mutations of KIT in familial testicular germ cell tumours

“…There are several risk factors for TGCT including previously diagnosed TGCT, undescended testis (UDT) and a family history of the disease. TGCT has been one of the highest familial relative risks of any cancer syndrome with reported increased risks of 8 -10-fold to brothers and 4 -6-fold to fathers (Forman et al, 1992;Heimdal et al, 1996). We previously described linkage of familial testicular cancer to a locus (TGCT1) at Xq27 (Rapley et al, 2000).…”