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Background: It is recognized that FMR1 premutation expansions are associated with premature ovarian failure (POF), but the role of smaller repeats at the boundary of premutation and normal is less clear.Methods: We have therefore investigated the incidence of these intermediate sized FMR1 CGG repeats (35-58 repeats) in a series of 366 women ascertained because of menopause before the age of 40.Results: We found no significant difference in the incidence of intermediates in cases compared with controls. Thus, we were unable to replicate previous studies showing a positive association, despite a significantly larger sample size.Conclusions: We therefore conclude that intermediate sized FMR1 CGG repeat alleles should not be considered a high-risk factor for POF based on current evidence. [ABSTRACT FROM AUTHOR]

Background: Men with Klinefelter syndrome have one or more extra X chromosomes and have endocrine abnormalities. Case reports have led to suggestions that men with Klinefelter syndrome have elevated risks of several cancers, but published cohort studies have been relatively small. We conducted a nationwide cohort study to examine these risks. Methods: We followed a cohort of 3518 men who had been cytogenetically diagnosed with Klinefelter syndrome in Britain from 1959 through 2002 and compared their cancer incidence and mortality with that of men in the national population. All statistical tests were two-sided. Results: The standardized mortality ratio (SMR) for all cancers was 1.2 (95% confidence interval [CI] = 1.0 to 1.4). Compared with the general population, men with Klinefelter syndrome had higher mortality from lung cancer (SMR = 1.5, 95% CI = 1.0 to 2.0), breast cancer (SMR = 57.8, 95% CI = 18.8 to 135.0), and non-Hodgkin lymphoma (SMR = 3.5, 95% CI = 1.6 to 6.6) and lower mortality from prostate cancer (SMR = 0, 95% CI = 0 to 0.7). The standardized mortality ratios were particularly high for breast cancer among men with 47,XXY mosaicism (SMR = 222.8, 95% CI = 45.9 to 651.0) and for non-Hodgkin lymphoma among men with a 48,XXYY constitution (SMR = 36.7, 95% CI = 4.4 to 132.5). The cancer incidence data corroborated these associations. Conclusions: These results support a hormonal etiology for breast cancer in men and for prostate cancer and suggest that men with Klinefelter syndrome may be at substantially elevated risks for non-Hodgkin lymphoma, breast cancer, and, perhaps, lung cancer. [ABSTRACT FROM AUTHOR]