Closer Kinship linked with Reproductive Success

In a paper published 7 Feb 2008, deCODE scientists establish a substantial and consistent positive correlation between the kinship of couples and the number of children and grandchildren they have. The study, which analyzes more than 200 years of deCODE's comprehensive genealogical data on the population of Iceland, shows that couples related at the level of third cousins have the greatest number of offspring. For example, for women born between 1800 and 1824, those with a mate related at the level of a third cousin had an average of 4.04 children and 9.17 grandchildren, while those related to their mates as eighth cousins or more distantly had 3.34 children and 7.31 grandchildren. For women born in the period 1925-1949 with mates related at the degree of third cousins, the average number of children and grandchildren were 3.27 and 6.64, compared to 2.45 and 4.86 for those with mates who were eighth cousins or more distantly related.

The findings hold for every 25-year interval studied, beginning with those born in the year 1800 up to the present day. Because of the strength and consistency of the association, even between couples with very subtle differences in kinship, the authors conclude that the effect very likely has a biological basis, one which has yet to be elucidated. The paper, 'An association between the kinship and fertility of human couples,' is published online in Science magazine at www.sciencemag.org.

This study provides the most comprehensive answer yet to the longstanding question of how kinship affects fertility in humans. Previous studies in other parts of the world have suggested that the two phenomena are positively correlated, though confounding variables, such as the impact of socioeconomic status on the size of families or age at marriage, have made the results difficult to interpret. The analysis of such a long-term series of data from Iceland effectively eliminates these variables by encompassing an entire population which has historically been highly homogeneous both culturally and economically. Moreover, the results are strikingly consistent from eras in which Iceland was a predominantly poor and rural country, to the present-day era of a highly urbanized society with one of the highest standards of living in the world.

The authors note that the findings are somewhat counterintuitive from an evolutionary perspective because closely-related parents have a higher probability of having offspring homozygous for deleterious recessive mutations, although closer parental kinship can also decrease the likelihood of immunological incompatibility between mother and offspring, for example in rhesus factor blood type. Perhaps most importantly, today's findings also suggest that the recent and dramatic demographic shift experienced in Iceland - from a rural society to a highly urbanized one - may serve to slow population growth, as individuals are exposed to a much broader range of distantly related potential mates. If so, this could be of relevance to slowing population growth in the many other - and much more populous - societies around the world undergoing transition from closely-knit rural societies to more urbanized ones. Indeed, the UN estimates that in the 2007-2008 period the majority of the world's population will, for the first time in human history, live in town and cities.

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Stress during Pregnancy associated with Schizophrenia of Children

A recent article in the Archives of General Psychiatry reports that women who undergo an extremely stressful event during the first three months of pregnancy have an increased risk of having children who develop schizophrenia.

Researcher Ali S. Khashan of the University of Machester, England and colleagues note that there is some consensus that a mother's psychological state influences her unborn baby. "Severe life events during pregnancy are consistently associated with an elevated risk of low birth weight and prematurity." Schizophrenia is a disabling condition associated with abnormal brain structure and function, and it is believed to begin in early brain development. Risk of the condition is influenced by susceptibility genes that can interact with environmental factors that occur during pregnancy.

The data are drawn from 1.38 million Danish births occurring between 1973 and 1995. A national registry linked mothers to close family members, and the registry informed researchers if mothers experienced stressful events during pregnancy such as a family member dying or receiving diagnosis of cancer, heart attack, or stroke. The data allowed the research team to follow children from their 10th birthday through June 30, 2005 or until they died, left the country, or received a schizophrenia diagnosis. During the study period, 21,987 mothers were exposed to the death of a relative during pregnancy, 14,206 were exposed to serious illness of a relative during pregnancy, and 7,331 of the offspring developed schizophrenia.

One result suggests a 67 percent greater risk of schizophrenia or related disorders among the children of women who experienced the death of a relative during the first trimester of pregnancy. The researchers note that if the death of a relative occurred up to six months before conception or any other time during pregnancy, the event was not associated with a risk for schizophrenia. In addition, a mother's exposure to a relative's serious illness is also not linked to schizophrenia.

Only for individuals without a family history (parents, grandparents or siblings) of mental illness was there a significant association between a family death and risk of schizophrenia.

The authors conclude that "risk associated with exposure to a well-defined, objective stressful event confined to the first trimester of pregnancy suggests a number of possible mechanisms." They suggest a possible effect on the fetus' brain of chemicals released by the mother's brain when she experiences stress. During early pregnancy, the protective barriers between the mother and fetus are not fully constructed, and the effects may be strongest.

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Measles, Mumps, and Rubella Vaccine is not linked to Autism Spectrum Disorders

The previously supposed link between autism the MMR jab, a vaccination against measles, mumps, and rubella, has been discredited, according to a study published in the Archives of Disease in Childhood on February 5, 2008. The MMR vaccine had been linked to the development of autism in the light of a 1998 publication, which has since been discredited by the scientific community.

Autism spectrum disorders are a set of psychological conditions that are similar to autism, characterized by abnormal social interaction, restricted interests, and repetitive behavior. They are found in approximately 6 to 12 cases per 1000 children depending on the specific diagnostic criteria that are applied.

The group studied was taken from a population of approximately 57,000 in one area of Southern England. Almost 250 children, born between 1990 and 1991 and aged between 10 and 12, were selected for examination. Of these: 98 children had an autism spectrum disorder; 52 were characterized as children with special educational needs, but no evidence of autism spectrum disorders; and 90 children were developing normally. A set-back or regression early in development had been experienced by some of the autistic children. All of the children in the sample had been administered the MMR vaccine, but not all had been given both doses.

The study analyzed blood samples from each child to investigate the presence of any circulating measles virus or increased antibody levels. Such results might indicate the presence of persistent measles infection or an abnormal immune response. this examination revealed no significant difference between the two groups of children. This conclusion was not affected by whether the child was administered both MMR doses, or by any regression of development.

Additionally, no bowel symptoms (entercolitis) were found in the autistic children, regardless of any early regression. Notably, autistic children and children with special educational needs had fewer instances of the second vaccination. This could reflect parental concern about vaccination following the diagnosis of a developmental abnormality.

This is now the third, and largest, study which has failed to show a link between the MMR jab and autism, note the authors.

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Folate Deficiency is associated with a Three-Fold Increased Risk of Dementia

Among elderly people, lower levels of folate can be associated with a three-fold increase in risk for dementia, claims a study published in the Journal of Neurology, Neurosurgery, and Psychiatry, part of the British Medical Journal Specialist Journals, on February 5, 2008.

Folate, vitamin B12, and the protein homocysteine are involved in reactions that are needed to produce several chemicals, including some neurotransmitters, lipids, and nucleotides. Previously, studies have shown a link between deficiencies in these chemicals and the prevalence of dementia, however, the results have been controversial because of the physical changes dementia often creates. High levels of homocysteine have also been associated with cardiovascular disease.

In this study, the researchers followed 518 people over 2 years (2001-2003), tracking the development of dementia within the population. All participants were more than 65 years old and lived in one rural or one urban area in the south of the country. To do this, at the beginning and the end of the two year period, validated tests were run to test for any dementing illness. Additionally, blood tests were taken to assess folate, vitamin B12

Similarly, blood tests were taken to assess levels of folate, vitamin B12, and homocysteine levels, and the changes with time were observed. At the beginning of the period, almost one in five participants showed high levels of homocysteine, almost the same had low levels of vitamin B12, and 3.5% were deficient in folate. Higher levels of folate were associated with higher vitamin B12 levels and lower homocysteine.

At the end of the study, 45 of the participants had developed dementia. Of these, 34 had been diagnosed with Alzheimer's disease, seven with vascular dementia, and four with "other" types of dementia. Dementia showed more prevalence in older patients, in the relatively uneducated, the inactive, and those with deposits of the protein ApoE.

Dementia onset was more likely in those who were older, relatively poorly educated, inactive, and had deposits of ApoE, a protein associated with the breakdown of lipids. It was also much more likely in those whose folate levels fell further over the two years while homocysteine levels increased. Individuals with folate deficiency at the start of the study were at risk for dementia almost 3.5 times more than others.

This suggests, according to the authors, that changes in micronutrients such as folate could be linked with the other typical signs that lead up to dementia, such as weight loss and low blood pressure. Weight loss could indicate a dietary change in quality or quantity of food intake, but it is unlikely to itself change the levels of micronutrients in the blood.

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HPV-Linked Oral Cancer in Men Increasing

A new study by researchers in the US suggests that the human papillomavirus (HPV) causes as many cases of oral cancer in men as tobacco and alcohol and will overtake the latter within the next ten years. They suggest the main reasons are changes in men's sexual behavior and the decline in oral cancers not caused by HPV.

The study is published in the February 1st issue of the Journal of Clinical Oncology and is the work of researchers at the Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, Maryland, and the Johns Hopkins Medical Institutions, Baltimore, also in Maryland.

HPV is known to cause cervical cancer in women, and there are vaccination programs in many countries, including the US, to immunize girls and young women against the strains of HPV that are thought to cause over 70 per cent of cervical cancers, for which there are 12,000 new cases and nearly 4,000 deaths in the US alone every year.

Previous research has already shown there is a risk of a range of genital and oral cancers in men also resulting from HPV infection, but as yet there are no immunization programs for men against HPV.

The only vaccine against HPV is the drug Gardasil, made by Merck & Co. According to an Associated Press (AP) report at the weekend, the drug company will be asking for the US Food and Drug Administration (FDA) to approve the vaccine for boys later this year.

So far, the primary argument for vaccinating men has been to stop the virus spreading to women and cutting down cervical cancer cases. But research on men is catching up, and there is mounting evidence that vaccinating boys will also benefit men directly. Apart from oral cancer, HPV also causes genital warts, penile and anal cancer.

Study co-author, Dr. Maura Gillison of Johns Hopkins University, told the AP news agency that:

"We need to start having a discussion about those cancers other than cervical cancer that may be affected in a positive way by the vaccine."

Gillinson led a study published in May 2007 that suggested people who had oral sex with 5 or more partners during their lifetime had a much greater chance of having throat cancer and that the cause was most likely to be a well known strain of HPV.

In this new study, Gillinson and colleagues examined nearly 46,000 cases of oral cancer occurring between 1973 and 2004 whose data is held by the National Cancer Institute in nine Surveillance, Epidemiology, and End Results program registries. They split the cases into two groups: those linked to HPV (over 17,500) and those that were not (over 28,000).

The results showed that:

* HPV-related oral cancers were diagnosed at younger ages than HPV-unrelated ones (mean ages at diagnosis were 61.0 and 63.8 years respectively).

* Incidence of HPV-related oral cancers rose significantly from 1973 to 2004, particularly among white, younger men.

* This compared to a stable, unchanging incidence of HPV-unrelated oral cancers from 1973 to 1982, and a declining rate after that.

* Improvements in 2-year survival rates from radiation treatment were more pronounced for HPV-related cancers than HPV-unrelated ones.

The researchers concluded that:

"The proportion of OSCCs that are potentially HPV-related increased in the United States from 1973 to 2004, perhaps as a result of changing sexual behaviors. Recent improvements in survival with radiotherapy may be due in part to a shift in the etiology of OSCCs."

OSCC stands for oral squamous cell carcinoma, by far the most common form of oral cancer.

According to the AP report, a cause-effect relationship between oral sex and HPV-related cancers is not proven, and some experts have even suggested unwashed hands could also be a risk factor.

Gillinson and colleagues suggested sex was an explanation for the rise in male upper throat cancers. However, HPV-related upper throat cancers has gone down significantly in women in the last 30 years.

There is no evidence to suggest that Gardasil will work in men. Merck are doing a study on the effectiveness of Gardasil for protecting against genital warts, anal and penile cancer in men, but not oral cancers, a Merck spokesperson told the AP, although they will be considering other studies in the future.

It would appear that more studies are needed on the effect of HPV in men, to bring the mountain of evidence up to that already available for its effect on women, and perhaps make the case for male vaccine development equally compelling.

There are about 40 sexually transmitted HPV strains, of which 13 or so are known to cause cancer in men and women. Gardasil does not "cure" infection once it occurs, but it can block 4 of the strains known to cause the vast majority of cervical cancer cases from infecting the body. That is why HPV vaccination programs are aimed at girls before they become sexually active.

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