Cancer incidence in women with Turner syndrome in Great Britain: a national cohort study

Turner syndrome, one of the most common cytogenetic abnormalities, is characterised by complete or partial X-chromosome monosomy. Cancer risks in women with Turner syndrome have not been clearly established. We aimed to compare the risk of cancer in women with this syndrome with that of the general population.We formed a national cohort of 3425 women who were cytogenetically diagnosed with Turner syndrome in Great Britain between 1959 and 2002. Identifying information for these patients was sent to the National Health Service Central Register (NHSCR) for England and Wales and to the NHSCR for Scotland. Individuals who were identified on this register were followed-up for cancer incidence. Standardised incidence ratios (SIRs) and 95% CIs were calculated on the basis of the number of cancers observed compared with that expected based on national incidence rates. Cumulative risk estimates were obtained by use of the Kaplan-Meier method.A total of 58,299 person-years were accrued during the study, with a mean of 17.0 years (SD 8.6) follow-up per patient. 73 malignancies other than non-melanoma skin cancer occurred (SIR 0.9 [95% CI 0.7-1.2]). Risks were significantly increased for tumours of the CNS (n=13; 4.3 [2.3-7.4]), especially for meningioma (n=7; 12.0 [4.8-24.8]) and childhood brain tumours (n=3; 10.3 [2.1-30.1]), and for cancers of the bladder and urethra (n=5; 4.0 [1.3-9.2]) and eye (n=2; 10.5 [1.3-37.9]), compared with the general population. However, the risk of breast cancer was significantly decreased (n=10; 0.3 [0.2-0.6]). The SIR for cutaneous melanoma was 2.2 (95% CI 1.0-4.4; n=8), and one of the ocular cancers was a melanoma. The risk of corpus uteri cancer was significantly increased at ages 15-44 years (n=3; 8.0 [1.6-23.2]). During follow-up, five women, all with a Y-chromosome lineage, developed gonadoblastoma of the ovary, corresponding to a cumulative risk of 7.9% (95% CI 3.1-19.0) by age 25 years in this group.This study shows that, in addition to having an increased risk of gonadoblastoma, women with Turner syndrome seem to be at increased risk for meningioma and childhood brain tumours, and possibly bladder cancer, melanoma, and corpus uteri cancer, but are at a decreased risk for breast cancer. Reasons for these risks might relate to genetic and hormonal factors or to the effects of hormonal treatments given to women with Turner syndrome.