Elsevier

The Lancet Oncology

Volume 9, Issue 3, March 2008, Pages 239-246
The Lancet Oncology

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

https://doi.org/10.1016/S1470-2045(08)70033-0Get rights and content

Summary

Background

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.

Methods

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.

Findings

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.

Interpretation

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.

Introduction

Turner (Ullrich-Turner) syndrome affects about 1 in 2000 live-born girls.1 The condition is characterised by complete or partial X-chromosome monosomy. Typical clinical features are short stature, ovarian dysgenesis with concomitant primary amenorrhoea, and lymphoedema. The phenotype is thought to be the result of haploinsufficiency of genes on the X chromosome that escape X-inactivation in early embryogenesis.2 Women with Turner syndrome have increased gonadotropin concentrations from infancy and low concentrations of oestrogens. Growth-hormone treatment is often given during adolescence to increase attained height and oestrogen-replacement treatment is given to initiate and sustain sexual maturation.

The risk of cancer in women with Turner syndrome has been little studied, but is important because the hormonal abnormalities and treatments associated with this syndrome might affect the risk of hormone-related cancers, and the chromosomal abnormality itself might affect cancer risk. Knowledge of this risk is also important in terms of counselling parents and probands on the disease and its prognostic implications, and for clinical and screening practice during the follow-up of these patients. Case reports3 have suggested that women with a Turner syndrome karyotype that includes a Y chromosome, such as 45,X/46,XY mosaicism, are at high risk of gonadoblastoma, a rare neoplasm that occurs almost exclusively in dysgenetic gonadal tissue; although a recent population-based study suggested lower risks than previously estimated.4 Furthermore, an increased susceptibility to neuroblastoma and related neurogenic tumours in childhood and early adulthood has been reported in hospital case series and reviews of case reports.5, 6 Case reports have also shown that patients with Turner syndrome might be at increased risk of endometrial cancer, due to long-term oestrogen-replacement treatment, although endometrial cancer in untreated patients has also been described.7, 8 The possibility of increased risks of several other cancers has also been suggested, but publication bias can over-emphasise coincidental findings. Few prospective studies of cancer occurrence in women with Turner syndrome have been reported. Mortality, including that from cancer, has been investigated in 156 patients with Turner syndrome in Scotland,9 and mortality and cancer incidence in an extended cohort of 285 patients in Scotland and England has also been studied.10 In Denmark, cancer incidence was investigated in a cohort of 597 women with Turner syndrome,11, 12 and cancer mortality in 781 women;1 a seven-times increased incidence of colon cancer was reported,11 but no significant associations with other cancers were noted. However, these studies were too small to investigate cancer risk in detail, and, therefore, leave many uncertainties on this topic.

We collected data from 25 cytogenetic centres in Great Britain over a period of 43 years to investigate the incidence of cancer in women with Turner syndrome, with the aim of including a much larger number of patients than previously studied.

Section snippets

Patients

Information on women who were diagnosed with Turner syndrome by postnatal cytogenetic tests was collected from all 27 regional cytogenetics centres in Britain, with the exception of two small centres who did not participate. Turner syndrome was defined as a karyotype with a 45,X cell line, or a structurally abnormal or absent short arm of the X chromosome. Records were collected for as far back in time as records had been maintained. Patients from three centres ascertained over a shorter time

Results

A total of 4909 women cytogenetically diagnosed with Turner syndrome between 1959 and 2002 were identified. Of these, 1287 could not be flagged on the NHSCR because insufficient identifying information was available, especially date of birth (n=712) or full name (n=223), or because the full name and date of birth was insufficiently specific to find a match on the NHSCR (n=352). A further 127 women were excluded from the study because of unknown year of cytogenetic testing, and 61 were excluded

Discussion

In our cohort of women with Turner syndrome, the overall risk of cancer was similar to that expected in the general population. Site-specific risks were, however, significantly increased for meningeal tumours, childhood brain tumours, bladder and urethra cancer, and ocular cancer, and significantly decreased for breast cancer. A significantly increased risk of cancer of the vagina and vulva was also noted, but this risk was not significant after excluding from the analyses the first 12 months

References (35)

  • PB Clement et al.

    Atypical polypoid adenomyoma of the uterus associated with Turner's syndrome. A report of three cases, including a review of “estrogen-associated” endometrial neoplasms and neoplasms associated with Turner's syndrome

    Int J Gynecol Pathol

    (1987)
  • WH Price et al.

    Mortality ratios, life expectancy, and causes of death in patients with Turner's syndrome

    J Epidemiol Community Health

    (1986)
  • AJ Swerdlow et al.

    Mortality and cancer incidence in persons with numerical sex chromosome abnormalities: a cohort study

    Ann Hum Genet

    (2001)
  • H Hasle et al.

    Occurrence of cancer in women with Turner syndrome

    Br J Cancer

    (1996)
  • International Statistical Classification of diseases and related health problems, 9th revision

    (1977)
  • NE Breslow et al.

    Statistical methods in cancer research. Volume II—the design and analysis of cohort studies. IARC scientific publication, no. 82

    (1987)
  • EL Kaplan et al.

    Nonparametric estimation from incomplete observations

    J Am Stat Assoc

    (1958)
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