New research may help explain why multiple sclerosis rates have risen sharply in the U.S. and some other countries among women, while rates appear stable in men.The study could also broaden understanding of how environmental influences alter genes to cause a wide range of diseases. The causes of multiple sclerosis (MS) are not well understood, but experts have long suspected that environmental factors trigger the disease in people who are genetically susceptible. In the newly published study, researchers found that women with MS were more likely than men with MS to have a specific genetic mutation that has been linked to the disease.
Women were also more likely to pass the mutation to their daughters than their sons and more likely to share the MS-susceptibility gene with more distant female family members. If genes alone were involved, mothers would pass the MS-related gene to their sons as often as their daughters, said researcher George C. Ebers, MD, of the University of Oxford. Ebers’ research suggests that the ability of environmental factors to alter gene expression — a relatively new field of genetic study known as epigenetics — plays a key role in multiple sclerosis and that this role is gender-specific.
The theory is that environmental influences such as diet, smoking, stress, and even exposure to sunlight can change gene expression and this altered gene expression is passed on for a generation or two. “The idea that the environment would change genes was once thought to be ridiculous,” Ebers says. “Now it is looking like this is a much bigger influence on disease than we ever imagined.”
The study by Ebers and colleagues included 1,055 families with more than one person with MS. Close to 7,100 genes were tested, including around 2,100 from patients with the disease. The researchers were looking for MS-specific alterations in the major histocompatibility complex (MHC) gene region. They found that women with MS were 1.4 times more likely than men with the disease to carry the gene variant linked to disease risk. A total of 919 women and 302 men had the variant in the MHC region, compared to 626 women and 280 men who did not have it.
The study appeared in the Jan. 18 issue of Neurology.
Epigenetics is not evolution. Genetic alterations linked to environmental assaults can be passed down for a generation or two, but DNA usually rights itself over time, Ebers says. “This may explain why we hardly ever see MS in families over more than three generations,” he says. Earlier studies by Ebers and colleagues suggest that vitamin D deficiency may be the environmental stressor that triggers the MS-linked gene alterations. Rates of the disease are highest among people living farthest from the equator, and there is widespread speculation that lack of vitamin D due to low sun exposure may explain this. Other than Ebers’ research team, Orhun Kantarci, MD, of the Mayo Clinic in Rochester, Minn., is one of the few researches studying epigenetics as it relates to multiple sclerosis.
Kantarci calls the new research a potentially important piece of the puzzle to explain the gender difference in MS, but he adds that the research must be replicated. “This study provides more questions than answers, but it is very interesting,” he says. “We are learning that inheritance isn’t as simple as [Gregor] Mendel described.”
Prostate cancer is the second most common cause of cancer related deaths in men. Previous cell and animal research suggests that genistein, a potent soy isoflavone, may prevent the spread of prostate cancer. Now research reports that a genistein-derived drug may help prevent the spread of prostate cancer in men with prostate cancer.
The study, presented at the Ninth Annual American Association for Cancer Research Frontiers in Cancer Prevention Research Conference, investigated the effect of the genistein-drug in men with localized prostate cancer. Researchers at the Robert H. Lurie Comprehensive Cancer Center of Northwestern University administered the genistein-drug once daily to 38 men with localized prostate cancer one month before prostate surgery.
The participant’s prostate cancer cells were analyzed after surgery. The researchers found an increased expression of genes that stop cancer cell spread (metastasis). Furthermore, there was a decreased expression of genes that enhance metastasis.
“The first step is to see if the drug has the effect that you want on the cells and the prostate, and the answer is ‘yes, it does,'” says lead researcher Raymond Bergan, MD, professor of hematology and oncology at Northwestern University Feinberg School of Medicine, in a news release. “All therapies designed to stop cancer cell movement that have been tested to date in humans have basically failed have because they have been ineffective or toxic. If this drug can effectively stop prostate cancer from moving in the body, theoretically, a similar therapy could have the same effect on the cells of other cancers.”
Previous studies have suggested that the fifty percent of the population who have a GSTM1 gene gain more benefit from eating broccoli than those who lack this gene. The study showed that the presence of the GSTM1 gene had a profound effect on the changes in gene expression caused by eating broccoli.
This study fills the gap between observational studies and studies with cell and animal models. While observational studies have shown that diets rich in cruciferous vegetables may reduce the risk of prostate cancer and other chronic disease, they do not provide an explanation of how this occurs. Evidence from animal and cell models has sought to provide an explanation, but these studies are usually based on high doses that would not normally be experienced as part of the diet.
The results of the study suggested that relatively low amounts of cruciferous vegetables in the diet – a few portions per week – can have large effects on gene expression by changing cell signalling pathways. These signalling pathways are the routes by which information is transmitted through a molecular cascade which amplifies the signal to the nucleus of the cell where gene expression occurs.
The Norwich team are currently planning a larger study with men with localised prostate cancer, and will compare the activity of standard broccoli with the special variety of high glucosinolate broccoli used in the current study.
Designer studies for health promotion
“Other fruits and vegetables have been shown to also reduce the risk of prostate cancer and are likely to act through other mechanisms,” says Professor Mithen.
“Once we understand these, we can provide much better dietary advice in which specific combinations of fruit and vegetable are likely to be particularly beneficial. Until then, eating two or three portions of cruciferous vegetable per week, and maybe a few more if you lack the GSTM1 gene, should be encouraged.”