Mortality and cancer incidence in males with Y polysomy in Britain: a cohort study

Abstract

The mortality and cancer incidence risks among males with Y polysomy are unknown because there have been no large long-term cohort studies carried out of such men. We conducted a cohort study of 667 men diagnosed with the abnormality in Britain since 1959 to compare their mortality and cancer incidence rates with those of the general population. Sixty deaths occurred during follow-up to December 2005, twice the number expected from general population rates (standardised mortality ratio (SMR) = 2.0 (95% confidence interval (CI) 1.5-2.6)). Significantly raised mortality was observed for diseases of the nervous system (SMR = 7.0, 95% CI: 2.3-16.4), circulatory system (SMR = 2.1, 95% CI: 1.3-3.2), respiratory system (SMR = 4.0, 95% CI: 1.8-7.5), genitourinary system (SMR = 10.2, 95% CI: 1.2-36.9), and congenital anomalies (SMR = 11.9, 95% CI: 3.2-30.5). Four of the five nervous system deaths were from epilepsy, the risk of death from this condition being more than 20-fold raised. The rates of cancer incidence and mortality among these men was not significantly different from those in the general population. This study provides evidence that mortality rates from several specific causes are raised among men with Y polysomy. The use of these data in genetic counselling should be cautious particularly for cases of Y polysomy that are detected prenatally. Further investigations are required to confirm these findings and to elucidate the possible role of genes on the Y chromosome in the aetiology of these causes of death.

An Opportune Life: 50 Years in Human Cytogenetics

“…They also have increased mortality from diseases of the circulatory system, respiratory system, and genitourinary system as well as congenital abnormalities. In contrast, their cancer incidences are not significantly different from those in the general population (19).…”

Socio‐economic factors affect mortality in 47,XYY syndrome—A comparison with the background population and Klinefelter syndrome

“…We estimate that only about 20% of the entire population of males with 47,XYY are diagnosed in Denmark. There is only one other study presenting epidemiological data [Higgins et al, 2007], and if one makes a crude extrapolation of their data (47,XYY, n ¼ 609, approximate size of male UK population 29,000,000), there are 2.1 diagnosed 47,XYY per 100,000 males in the UK in comparison with 14 diagnosed 47,XYY per 100,000 males presented here. This low rate suggests that the estimates on mortality in the UK study are more precarious than the one we present.…”

“…However, the estimates presented from UK and Denmark are overlapping and should therefore probably both be viewed as valid. We also know that late diagnosis and non-diagnosis is a problem with all sex chromosome syndromes [Gravholt et al, 1996;Abramsky and Chapple, 1997;Swerdlow et al, 2001Swerdlow et al, , 2005aBojesen et al, 2003;Stochholm et al, 2006Stochholm et al, , 2010aEl-Mansoury et al, 2007;Higgins et al, 2007] and we speculate that this will also be the case for 47,XYY syndrome in other countries. Males identified in a clinical setting as studied here are not necessarily comparable to those identified in surveys, basically due to the highly variable phenotype among 47,XYY persons spanning from a normal phenotype to a more abnormal phenotype.…”

“…It is estimated that a sex chromosomal abnormality occurs in 1 per 400 births [Linden et al, 1995]. We recently published epidemiological data based on nationwide follow-up showing significant delay to diagnosis, reduced life expectancy and an increased total and cause-specific mortality [Stochholm et al, 2010a], also shown by others [Higgins et al, 2007], and we documented that only 14 per 100,000 males were diagnosed, emphasizing that significant under-diagnosis is present for all sex chromosome aberrations [Gravholt et al, 1996;Abramsky and Chapple, 1997;Bojesen et al, 2003;Stochholm et al, 2006Stochholm et al, , 2010b. We also showed that despite conventional thinking that 47,XYY is a diagnosis made by pediatricians, the average age at diagnosis was 17 years with a wide age range [Stochholm et al, 2010a], and we speculate that similar patterns of diagnosis may be present in other countries.…”

A non-mosaic isodicentric Y chromosome resulting from breakage and fusion at the Yq pseudo-autosomal region in a fetus

“…Significant raised mortality has been observed for disease of various organ systems (nervous system, circulatory system, respiratory system, genitourinary system, and congenital anomalies) in men with an extra Y chromosome. However, the cancer incidence and mortalities are not increased [17]. Emerging evidence also suggested higher rates of problem behaviors and hyperactive/impulsive symptoms [18].…”