NEWS

Gender Differences in Cancer That Don’t Make Sense—Or Do They?

Jean McCann

It is obvious why there are no cases of prostate cancer among women and almost nonexistent incidence rates of breast cancer among men. But why is there a difference between the sexes in the rates of non-Hodgkin’s lymphoma or a type of brain cancer?

When he looked at the latest figures on gender differences in cancer, Harmon Eyre, M.D., chief medical officer of the American Cancer Society, said that he was puzzled by some of the differences.

Although some differences are hormonally related, there are probably many more differences between the sexes that are caused by behavior rather than sex hormones.

Eyre said that although there are cases in which the incidence of cancer is higher in women, there are far more in which the men outstrip the women, largely because of different smoking and drinking behaviors, and in some cases, occupational exposures.

Stomach cancer is one example. Eyre said there is an ongoing shift in stomach cancer in the United States to Barrett’s esophagus, and the development of cancer in the gastroesophageal junction is increasing while the adenocarcinomas of the stomach are decreasing.

"There’s a lot of debate about why this is happening—reflux esophagitis is the presumed cause, and it’s more common in men than women," he said. "This is related presumably to a combination of things that create reflux, like late night eating, drinking of alcohol and coffee, and smoking."

For liver cancer, the incidence in men is estimated at about 10,000 versus 5,300 in women this year, again probably related to more alcohol consumption, which he said also accounts for the greater incidence of head and neck cancers in men.

For some cancers, there is no ready explanation for differences between the sexes. There will be an estimated 31,700 new cases of non-Hodgkin’s lymphoma in men this year compared to only 23,200 in women—a 50% higher incidence. "I have zero ideas about why [there is a] difference, but it’s really quite striking," Eyre said.

Biologic Factors

Meningioma, a type of brain cancer, makes up about 15% of brain tumors. It is much more common in women, he said, probably because this particular tumor has estrogen and progestin receptors. For that reason, tamoxifen is sometimes part of the treatment for this kind of brain tumor. "It’s not highly effective, but clearly there’s a sex hormone difference in some tumors," he said. It illustrates that even though some cancers are not thought to be related to the sex of the patient, the hormonal environment is indeed relevant.

Malignant tumors of the thyroid are much more common in women than in men. Although the reason for this is not clearly spelled out, he said, it is known that women have more autoimmune disease than men, and this could explain some of the difference.

Women are also much more likely to get cancer of the gallbladder—about 4,000 new cases in women this year versus 2,900 in men. "It is widely accepted that women are more likely to have gallstones, and the association of chronic inflammation with gallstones and subsequent cancer of the bladder is well recognized," Eyre said.

But why?

Eyre said that women who are overweight are at higher risk, and historically women are more overweight than men. He added that differences in the metabolism of steroids and cholesterol in men and women is related in part to the estrogen and androgen difference.

In another look at sex differences in cancer, Michaela Kreuzer, M.D., of the Federal Office of Radiation Protection in Oberschleissheim, Germany, told a session of the World Congress on Lung Diseases held in Florence, Italy, in September that more men than women get squamous cell cancer of the lungs—the kind associated with smoking—than do women. She added that the gender mortality ratios have also been much higher in Europe than in the United States, with the highest in Southern Europe, with a ratio of about 8 to 1, versus 3 to 1 in the northern part of the continent.



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Dr. Michaela Kreuzer

 
Even so, women seem to run a relatively higher risk than men if they smoke, she said, citing a large U.S. case control study (J Natl Cancer Inst, Feb. 21, 1996, pp. 183–92). Overall, she said, women had a 1.5 times higher risk that could not be explained by body size or smoking history. On the other hand, she said, a case–control study she conducted and two Scandinavian studies showed no difference in risk between men and women, but she said the picture was confused by the fact that some included ex-smokers, and some did not.

She added, however, that some studies have shown gender differences at the cellular level, with relatively high aromatic hydrophobic DNA adducts in female as opposed to male lung cancer patients.

Hormonal factors, such as late age at menopause and estrogen replacement therapy, may also play a role in greater female susceptibility to tobacco carcinogens, she said. But, she added, the higher susceptibility of women to lung cancer is based on evidence from a limited number of studies, which are not always consistent. "The underlying mechanism is not yet clear," she said.


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