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

Abstract

Mortality and cancer incidence were assessed in a cohort of 1373 patients with numerical sex chromosome abnormalities diagnosed at three cytogenetics centres in Britain during 1959-90, and were compared with expectations from national rates. Four hundred patients with Turner's syndrome were followed, of whom 62 died, with a relative risk (RR) of death of 4.16 (95 % confidence interval (CI) 3.22-5.39). Turner's syndrome patients had greatly raised risks of death from diseases of the nervous, cardiovascular, respiratory, digestive and genitourinary systems. One hundred and sixty three deaths occurred among 646 patients with Klinefelter's syndrome with a 47,XXY constitution, giving an RR of 1.63 (1.40-1.91). Mortality in these patients was significantly raised from diabetes and diseases of the cardiovascular, respiratory and digestive systems. There was also significantly increased mortality for patients with X polysomy (RR l 2.11 (1.43-3.02)) and Y polysomy (RR l 1.90 (1.20-2.85)), the former with significantly increased mortality from cardiovascular disease and the latter from respiratory disease. The only significantly raised risks of cancer incidence or mortality in the cohort were for lung cancer and breast cancer in patients with Klinefelter's syndrome with a 47,XXY constitution, and non-Hodgkin's lymphoma in men with more than three sex chromosomes.

Loss of the Inactive X Chromosome and Replication of the Active X in BRCA1-Defective and Wild-type Breast Cancer Cells

“…Extra X chromosome dosage seems to be an event also in male breast tumors, in which the lack of Y chromosome and the duplication of X were often reported (18,(20)(21)(22)(23)(24). The role of X chromosome dosage in breast tumor development is further strengthen by the evidence that males with a 47, XXY karyotype have a 50-fold increased risk to develop a breast cancer respect to 46,XY males (25,26).…”

Unsuspected Klinefelter Syndrome Diagnosed during Oncologic Evaluation: A Case Series

“…In addition, a total of 2 breast cancer deaths was observed. 23 Many medical textbooks and several case reports suggest an association between KS and leukemia and lymphoma; however, this association has not been proven. A cohort study of 696 men with KS found no difference in the incidence of leukemia and lymphoma.…”

“…1,35 Smoking cessation should be emphasized, not only to potentially prevent vascular complications arising from diabetes but also to prevent lung cancer, which contributes to increased overall mortality. 23 It has also been suggested that men with KS be evaluated for specific learning disabilities. 5 Although overall intelligence may be within normal range, it has been noted that KS patients tend to have deficits in verbal and motor skills.…”

“…1 From early adolescence to age 30, men with KS have a substantially increased incidence of mediastinal germ cell tumors. 30 If young men with KS experience 23 Information on smoking habits was not obtained as part of this study, leaving open the possibility that these men smoked more than the general population. In addition, a total of 2 breast cancer deaths was observed.…”

“…1 Karyotyping of men with breast cancer has shown that men with KS have an increased risk of developing this malignancy. 23 In a retrospective study of 93 unselected male breast cancer patients, 7.5% had KS. This prevalence is double that cited in previous studies, possibly because of these authors' use of fluorescence in situ hybridization with X and Y chromosome-specific DNA probes.…”