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Dads More Likely Than Moms to Pass on MS

Men with multiple sclerosis are more than twice as likely than women with the illness to pass it on to their children, U.S. researchers report.

"When we looked at a large population of MS patients, when there was a parent and a child who had MS in a family, the child with MS got the disease twice as often from the father rather than the mother," researcher Dr. Brian Weinshenker, a Mayo Clinic neurologist, said in a prepared statement.

Reporting in the July 25 issue of Neurology, Weinshenker and his colleagues theorized that this may be because men may have a greater "genetic load" of MS genes compared to women.

"The hypothesis of this study is that men are more resistant to MS, so they need stronger or a larger number of genes in order to develop MS, and then pass these genes to their children," study author Dr. Orhun Kantarci, a Mayo Clinic neurologist, said in a prepared statement.

The fact that men are more likely to pass MS to their children is not easily explained by hormonal differences between women and men or by genes on the sex chromosomes, Kantarci said.

The findings shouldn't affect how men with MS are counseled about the risk to their children, the researchers said. A child with an affected parent has about a 20-fold increased risk of MS. But the additional risk of having a father with the disease is not enough to change current patient counseling methods.

"The over-transmission by men is primarily of interest to scientists studying the mechanisms of genetic transmission of MS susceptibility," Kantarci said. The finding "may indicate that nontraditional, or so-called epigenetic factors, play some role in the transmission of MS," he theorized.

Eighty-five percent of MS cases have no known cause. Among 15 percent of MS patients, a family member within a generation is also affected by the disease. In familial cases, no single gene has been identified that strongly predisposes a person to MS.

"We know in women who have had breast cancer and have hormone-positive [tumors], taking tamoxifen improves their survival," Melnikow said. And, she added, it's well known that tamoxifen reduces breast cancer recurrence in women who had breast cancer by 47 percent with five years of treatment. "It's also been proved to reduce the incidence of breast cancer in women at high risk" by about 49 percent, she said.

However, "We took into consideration the fact that the breast cancers that are prevented by tamoxifen are mostly hormone receptor-positive cancer, and those cancers actually have a better prognosis than hormone-receptor negative cancers," Melnikow explained.

In other words, even though the drug may help prevent many cases of more curable hormone receptor-positive cancers, it is not effective in protecting against more deadly receptor-negative tumors. Added to that is the raised risk for endometrial cancer and blood clots among women taking tamoxifen. The end result is no difference in mortality for many high-risk women using the drug, the researchers concluded.

Meanwhile, the mathematical model found that the drug cost as much as $1.3 million per year of life saved, based on the U.S. price of the drug. That's a concern not only for public policy makers, she said, but also for individual women. For example, a patient living in the Sacramento area can expect to pay between $240 and $1,500 per year for tamoxifen.

The bottom line: "For most women, they don't think it is going to help improve survival," said Dr. Herman Kattlove, medical editor for the American Cancer Society who is familiar with the analysis. "If you are in the [high range] of the high-risk group, it may help survival. But 'may' is the operative word." The drug does decrease the chance of getting breast cancer, he added.

"Risk does matter," stressed Dr. Christy Russell, associate professor of medicine at the University of Southern California Keck School of Medicine, Los Angeles, and an American Cancer Society spokeswoman. "Women at the higher [end of] the risk range are more likely to benefit from the tamoxifen, in terms of reducing their risk of dying prematurely from breast cancer," she said.

And even among lower-risk women, she said, "It would be more acceptable to use tamoxifen if she had no uterus, because a lot of the concern about potential deaths revolved around uterine cancer."