Testicular cancer in twins: a meta-analysis

Abstract

In a meta-analysis of testicular cancer in twins, twins had a 30% increased risk (estimate 1.31, 95% CI 1.1 -1.6), providing indirect support for the hypothesis that in utero hormone variations influence risk of testicular cancer. The summary-estimate for dizygotic twins was 1.3 (1.0 -1.7) and for monozygotic or same sex twins 1.4 (1.2 -1.8). Testicular germ-cell cancer is either the most common or second most common cancer in men aged 15 -45, depending on country, and rates have been increasing substantially in developed countries over the past few decades (Huyghe et al, 2007). Despite attempts to identify risk factors, the aetiology remains unclear. Cryptorchidism, age (Garner et al, 2005), contra-lateral disease, and family history (Hemminki and Chen, 2006) are the only established risk factors. Both low and high birth weight may also be associated (Michos et al, 2007). Evidence from animal models (Newbold et al, 1987), and indirectly from human studies (reviewed in Grotmol et al, 2006), indicates that the susceptibility for testicular cancer is probably established in utero. The relative importance of environmental factors and genetic factors are not clear, but it is likely that both play an aetiological role (Oosterhuis and Looijenga, 2003). Although the mechanism is uncertain, it is thought that foetal exposure to unusually high oestrogen levels, or an imbalance of oestrogen and androgen levels, might contribute to an increased risk. Examining features of pregnancy, which can affect the levels of these hormones, may help to elucidate the aetiology of this cancer. Twinning is of interest, as twin pregnancies, perhaps particularly with dizygotic twins, result in higher maternal levels of serum oestrogens than with singleton pregnancies.Several studies have suggested an association between being a twin and testicular cancer, but as both testicular cancer and twinning are rare events, inferences have been limited by a lack of precision in most studies. We therefore aimed to improve the precision of the estimate of testicular cancer risk among twins by carrying out a meta-analysis of previously published studies. MATERIALS AND METHODSStudies published in English between 1961 and 2006 were identified through systematic searches of computerised bibliographic databases (Medline and Embase) using combinations of individual search terms and subject headings. We inspected the reference lists of studies retrieved from these initial searches for previously unidentified studies, which were then located on Medline to identify their subject headings. Further searches were then undertaken using these derived subject headings.We included all studies that had reported the risk of testicular cancer in twins compared with the general population or a specific single birth control group. Some studies did not provide a risk estimate for all male twins, instead reporting monozygotic and dizygotic twin risks separately (Braun et al, 1995;Swerdlow et al, 1997;Verkasalo et al, 1999), but if a total estimate could be calculated from t...

Trends in testicular germ cell cancer incidence in Australia

“…Exposure to a relative excess of estrogens or other endocrine disrupters during the first trimester of pregnancy may be an important risk factor, and this hypothesis is compatible with established histogenetic pathways of the development of fetal germ cells into intratubular neoplastic cells [18,19]. Possible sources of estrogen excess may include endogenous hormonal imbalances, and there is some evidence that conditions which increase maternal estrogen levels during pregnancy, such as twin pregnancies, primigravid state, and obesity, are associated with increased risk of testicular cancer [20,21].…”

Variants in or near KITLG, BAK1, DMRT1, and TERT-CLPTM1L predispose to familial testicular germ cell tumour

“…In brothers of cases, the risk is increased eight- to 10-fold 5 6. Interestingly, in dizygotic and monozygotic twin brothers of men with TGCT, 37-fold and 76.5-fold elevated risks of TGCT have been reported, respectively7; however, according to a recent meta-analysis, twins had only an approximately 30% increased risk of developing TGCT 8. Moreover, 2–5% of patients develop bilateral TGCT 9 10…”

Perinatal markers of estrogen exposure and risk of testicular cancer: follow-up of 1,333,873 Danish males born between 1950 and 2002

“…Other potential risk factors include a history of testicular cancer in fathers or brothers [8], white race compared to blacks and Asians [9,10], low or high maternal age [11,12], young paternal age [11], twinning [13,14], low and high birth weight [15], low birth order and small sibship size [16,17], preterm birth [18,19], severe nausea (hyperemesis) in pregnancy [20], bleeding and spotting in pregnancy [21], neonatal jaundice [22], and hormones, including diethylstilbestrol, given early in pregnancy [23,24]. However, results of many studies conducted to date have been inconsistent.…”