Risks of breast and testicular cancers in young adult twins in England and Wales: evidence on prenatal and genetic aetiology

Background Aetiology of breast and testicular cancers may have prenatal factors, possibly exposure of the fetus to high concentrations of maternal oestrogen. Dizygotic twinning probably involves high hormone concentrations, and therefore, dizygotic twins might be at raised risk of these cancers. The aetiologies of breast and testicular cancers have genetic components, for breast cancer, especially at younger ages. Twins of these probands may, therefore, be at high risk. We investigated risk in twins of patients with breast cancer at young ages or with testicular cancer. Methods We identified twins with breast cancer incident at ages younger than 45 years and with incident testicular cancer in England and Wales during 1971–89 by crossmatching national cancer-registration and births records. We determined zygosity by questionnaires to the patients. The twins of probands were followed up for cancer incidence and death. We analysed risks of breast and testicular cancer in dizygotic twins compared with monozygotic twins, and in monozygotic and dizygotic twins of probands. Findings We identified 500 twins with breast cancer and 194 with testicular cancer. We found a non-significantly raised risk of breast cancer in dizygotic compared with monozygotic twins younger than 30 years (odds ratio 2·3 [95% CI 0·9–5·9]) but not older. The overall risk of testicular cancer was significantly higher in dizygotic twins than in monozygotic twins (1·5 [1·1–2·2]) consequent on a risk for seminomas was high (3·2 [1·6–6·5]; p=0·001). Risk of breast cancer was significantly raised in female twins of probands (standardised incidence ratio 7·7 [4·9–12·2], p<0·001). The relative risk of breast cancer was 34·7 (9·5–126·5) in monozygotic twins of women in whom breast cancer had occurred before age 35 years. The cumulative risk of breast cancer for these twins by age 40 years was 29% (13–56). The relative risk of testicular cancer was 37·5 (12·3–115·6) in twins of men with testicular cancer. The cumulative risk by age 40 years in monozygotic twins of men with testicular cancer was 14% (4–46). Interpretation The higher risks of these cancers in dizygotic than in monozygotic twins support a prenatal aetiology, and are compatible with aetiology related to raised maternal concentrations of free, unbound oestrogens. The results for twins of probands have implications for genetic aetiology; appropriate clinical action for monozygotic twins needs consideration.