Wednesday, June 30, 2010

There was a statistically significant increase in the odds of Klinefelter syndrome with increasing paternal age

Arch Dis Child. 2010 Jun 28. [Epub ahead of print]

Case-control analysis of paternal age and trisomic anomalies.
De Souza E, Morris JK; EUROCAT Working Group.

Barts and The London School of Medicine and Dentistry, Queen Mary University of London, Wolfson Institute of Preventive Medicine, Charterhouse Square, London, UK.

Objectives To determine whether older paternal age increases the risk of fathering a pregnancy with Patau (trisomy 13), Edwards (trisomy 18), Klinefelter (XXY) or XYY syndrome. Design Case-control: cases with each of these syndromes were matched to four controls with Down syndrome from within the same congenital anomaly register and with maternal age within 6 months. Setting Data from 22 EUROCAT congenital anomaly registers in 12 European countries. Participants Diagnoses with observed or (for terminations) predicted year of birth from 1980 to 2005, comprising live births, fetal deaths with gestational age >/=20 weeks and terminations after prenatal diagnosis of the anomaly. Data include 374 cases of Patau syndrome, 929 of Edwards syndrome, 295 of Klinefelter syndrome, 28 of XYY syndrome and 5627 controls with Down syndrome. Main outcome measures Odds ratio (OR) associated with a 10-year increase in paternal age for each anomaly was estimated using conditional logistic regression. Results were adjusted to take account of the estimated association of paternal age with Down syndrome (1.11; 95% CI 1.01 to 1.23). Results The OR for Patau syndrome was 1.10 (95% CI 0.83 to 1.45); for Edwards syndrome, 1.15 (0.96 to 1.38); for Klinefelter syndrome, 1.35 (1.02 to 1.79); and for XYY syndrome, 1.99 (0.75 to 5.26). Conclusions There was a statistically significant increase in the odds of Klinefelter syndrome with increasing paternal age. The larger positive associations of Klinefelter and XYY syndromes with paternal age compared with Patau and Edwards syndromes are consistent with the greater percentage of these sex chromosome anomalies being of paternal origin.

PMID: 20584846 [PubMed - as supplied by publisher]

Supplemental ContentRelated citations
Trisomy 18 in Kuwait. [Int J Epidemiol. 1999]
Trisomy 18 in Kuwait.
Naguib KK, Al-Awadi SA, Moussa MA, Bastaki L, Gouda S, Redha MA, Mustafa F, Tayel SM, Abulhassan SA, Murthy DS.
Int J Epidemiol. 1999 Aug; 28(4):711-6. Down syndrome and paternal age, a new analysis of case-control data collected in the 1960s. [Am J Med Genet A. 2009]
Down syndrome and paternal age, a new analysis of case-control data collected in the 1960s.
De Souza E, Alberman E, Morris JK.
Am J Med Genet A. 2009 Jun; 149A(6):1205-8. Maternal age-specific risk of non-chromosomal anomalies. [BJOG. 2009]
Maternal age-specific risk of non-chromosomal anomalies.
Loane M, Dolk H, Morris JK, EUROCAT Working Group.
BJOG. 2009 Jul; 116(8):1111-9. Epub 2009 May 29.[Prenatal diagnostics of chromosomal aberrations Czech Republic: 1994-2007] [Ceska Gynekol. 2009]
[Prenatal diagnostics of chromosomal aberrations Czech Republic: 1994-2007]
Gregor V, Sípek A, Sípek A Jr, Horácek J, Langhammer P, Petrzílková L, Calda P.
Ceska Gynekol. 2009 Feb; 74(1):44-54. Review Epidemiology of double aneuploidies involving chromosome 21 and the sex chromosomes. [Am J Med Genet A. 2005]
Review Epidemiology of double aneuploidies involving chromosome 21 and the sex chromosomes.
Kovaleva NV, Mutton DE.
Am J Med Genet A. 2005 Apr 1; 134A(1):24-32. See reviews...


Saturday, June 26, 2010

ntists show children of older fathers face a higher risk of a type of lymphoma

Scientists show children of older fathers face a higher risk of a type of lymphoma

By Wayne Lewis

Risk of non-Hodgkin’s lymphoma is higher for children of older men, according to City of Hope researchers — a finding that adds to a growing body of evidence suggesting that men, too, may have a biological clock.

The study is one of the first to examine the relationship between parents’ age and their adult offspring’s likelihood of facing cancers of the blood and immune system. Yani Lu, Ph.D., a postdoctoral fellow in the Division of Cancer Etiology, led the study, which was released online in the American Journal of Epidemiology on June 3.

Yani Lu (Photo by p.cunningham)

“As a man, you may think, ‘I can have a baby at 50 or 60 and live long enough to see him go through college.’ But there may be other risks for your child down the line, and you may want to be conscious of those risks,” said Lu.

Lu’s research drew upon data from the California Teachers Study. Initiated in 1995, this project tracks the health, lifestyle choices and demographic information of nearly 133,500 female teachers and administrators in the California public schools’ retirement system. The teachers study is led by Leslie Bernstein, Ph.D., director of the Division of Cancer Etiology in the Department of Population Sciences and Lu’s mentor.

In the latest project, researchers focused on 110,999 women, 819 of whom had been diagnosed with a hematological malignancy. The study revealed that participants born to fathers older than age 40 faced a 59 percent greater risk of non-Hodgkin’s lymphoma compared to similar women born to fathers younger than 25.

“For adult-onset malignancies, people seldom think back” to factors early in life, Lu said. “Diagnosis for non-Hodgkin’s lymphoma occurs closer to the age of 70, so why would in utero factors be related to risk?”

In the study, the fathers’ age had no effect on risk for acute myeloid leukemia or multiple myeloma. Maternal age did not significantly influence risk for blood cancers.

Science has shown that the ticking biological clock is associated with a higher incidence of health issues in children of older mothers. These women face greater risk of miscarriage and increased risks of bearing children with low birth weight or serious health issues such as Down’s syndrome. A recent, large study suggested that children of women over 40 have a greater chance of having autism.

Similar findings among older fathers are scanty, although research going back almost 100 years suggests that these men are more likely to produce children with certain rare birth defects. Numerous studies also show that offspring of older men have a greater risk of developing schizophrenia.

As Lu noted, however, a burgeoning field of research suggests a father’s age at conception may play a more significant role in his progeny’s health than once thought. Recent investigations indicate that children of older fathers have a greater chance of prostate and breast cancers in adulthood as well as some blood cancers during childhood.

Lu believes the male biological clock might relate to mutations that can accumulate in a man’s reproductive cells over the course of a lifetime. Such cells divide more rapidly than a woman’s reproductive cells. More divisions lead to more chances for abnormalities to arise.

Older parental age also appears to be associated with longer length of offspring’s telomeres, the end caps on chromosomes, which might be linked to non-Hodgkin’s lymphoma risk, Lu suggested.

Because non-Hodgkin’s lymphoma is actually a cluster of related diseases with about 30 subtypes, Lu plans to examine how paternal age and other health factors during the early years of life influence risk for specific disease subtypes.

Sophia S. Wang, Ph.D., associate professor of population sciences, was the paper’s senior author. The National Institutes of Health and the California Breast Cancer Research Fund funded the research.


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Thursday, June 10, 2010

In females but not in males, increasing paternal age was associated with a linear increased risk of suicide

J Nerv Ment Dis. 2010 Jun;198(6):404-411.

Advanced Paternal Age, Mortality, and Suicide in the General Population.
Miller B, Alaräisänen A, Miettunen J, Järvelin MR, Koponen H, Räsänen P, Isohanni M, Kirkpatrick B.

*Department of Psychiatry and Health Behavior, Medical College of Georgia, Augusta, Georgia; daggerDepartment of Psychiatry, University of Oulu, Oulu, Finland; double daggerDivision of Epidemiology, Public Health, and Primary Care, Imperial College, London, United Kingdom; section signDepartment of Public Health and General Practice, University of Oulu, Oulu, Finland; and paragraph signDepartment of Psychiatry, University of Kuopio, Kuopio, Finland.

Advanced paternal age is a risk factor for adverse health outcomes in the offspring. In a population-based birth cohort from Finland, 10,965 singleton offspring born in 1966 and alive at age 1 were followed to age 39. Hazard ratios were calculated, adjusting for maternal age, gender, paternal social class, and maternal parity. In females but not in males, increasing paternal age was associated with a linear increased risk of suicide (hazard ratio [HR] = 1.13, 95% confidence interval [CI] = 1.04-1.24, p < 0.01) and all-causes mortality (HR = 1.06, 95% CI = 1.01-1.10, p = 0.02). Increasing maternal age was associated with a significantly decreased risk of suicide (HR = 0.93, 95% CI = 0.86-1.00, p = 0.04) and all-causes mortality (HR = 0.96, 95% CI = 0.93-1, p = 0.02) in the entire cohort. For paternal age >/=30, the population attributable risk percentage was 13.7% for all deaths and 7.5% for suicides. Parental age at birth may affect suicide and all-causes mortality risk in the offspring in the general population. The causal pathways and specific disorders associated with this increased mortality are largely unknown.

PMID: 20531118 [PubMed - as supplied by publisher]

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