RISKS OF BREAST AND TESTICULAR CANCERS IN YOUNG-ADULT TWINS IN ENGLAND AND WALES - EVIDENCE ON PRENATAL AND GENETIC ETIOLOGY

Background Aetiology of breast and testicular cancers may have prenata l factors, possibly exposure of the fetus to high concentrations of ma ternal oestrogen. Dizygotic twinning probably involves high hormone co ncentrations, and therefore, dizygotic twins might be at raised risk o f these cancers. The aetiologies of breast and testicular cancers have genetic components, for breast cancer, especially at younger ages. Tw ins of these probands may, therefore, be at high risk. We investigated risk in twins of patients with breast cancer at young ages or with te sticular cancer. Methods We identified twins with breast cancer incide nt at ages younger than 45 years and with incident testicular cancer i n England and Wales during 1971-89 by cross-matching national cancer-r egistration and births records. We determined zygosity by questionnair es 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 monozygoti c and dizygotic twins of probands. Findings We identified 500 twins wi th breast cancer and 194 with testicular cancer. We found a non-signif icantly raised risk of breast cancer in dizygotic compared with monozy gotic twins younger than 30 years (odds ratio 2.3 [95% CI 0.9-5.9]) bu t not older. The overall risk of testicular cancer was significantly h igher in dizygotic twins than in monozygotic twins (1.5 [1.1-2.2]) con sequent on a risk for seminomas was high (3.2 [1.6-6.5]; p=0.001). Ris k of breast cancer was significantly raised in female twins of proband s (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 wo men in whom breast cancer had occurred before age 35 years. The cumula tive 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 yea rs in monozygotic twins of men with testicular cancer was 14% (4-46).I nterpretation The higher risks of these cancers in dizygotic than in m onozygotic 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 ge netic aetiology; appropriate clinical action for monozygotic twins nee ds consideration.