Most cancers strike men, but reasons are enigmatic

February 9, 2012 — It is well known that most cancers strike men more often than women. In many cases these differences can be explained by known risk factors such as smoking, drinking, or occupational hazards. But more than one-third of the cancers that disproportionately strike one sex or the other—men, in particular—cannot be explained by known risk factors and seem to be associated with gender alone, according to research led by Gustaf Edgren, a research fellow in the Department of Epidemiology at Harvard School of Public Health (HSPH).

The new study, published online January 13, 2012 in the European Journal of Epidemiology, is the largest to date to examine the disparities in cancer rates between the sexes and what might account for them. Read the abstract.

According to the World Health Organization, there were 12.7 million new cancer cases around the world in 2008, with 6.6 million cases occurring in men and 6 million in women. The number is expected to increase to 21 million by 2030.

Edgren, senior author Ellen Chang of Stanford University Medical School, and researchers from the Karolinska Institute in Stockholm postulate that puzzling sex disparities in cancer rates are likely the result of some sort of intrinsic, sex-specific biological factors or a difference in susceptibility to risk factors. They add that if the causes of the disparities could be identified—and were modifiable—more than a third of cancers could be prevented.

“Not only do men have an increased risk of 32 of the 35 most common cancers, but, intriguingly, for many of these cancers the male excess risk is very strong. The risk has remained almost constant since at least the 1960s, and is completely enigmatic,” said Edgren. “We simply have no idea why.”

For their analysis, the researchers analyzed almost 15 million cases of cancer in 60 countries, drawing on a worldwide database of cancer statistics, Cancer Incidence in Five Continents.

Cancer strikingly more common in men

The researchers examined two broad questions. Of the 35 types of cancer in the study, they looked at which strike mostly men or mostly women, and quantified the disparity in each case. They also grouped the cancers according to known risk factors, focusing especially on factors that could contribute to gender differences.

Analyzing cancer rates alone, the researchers found that, for nearly half of the 35 cancers examined, men were struck by the disease twice as often as women. For five of the cancers, the male risk was fourfold. Those five cancers included cancers of the larynx, hypopharynx (the  bottom part of the throat), and lip; urinary bladder cancer; and Kaposi sarcoma (a rare form of skin cancer).

Risk factors often unclear

Next, researchers looked at risk factors for the 35 cancers. For 13 types—12 of which strike men more often than women—they found no known risk factors that could plausibly explain the sex disparities. In many cases, those disparities remained consistent over four decades. Some of those cancers included thyroid cancer, myeloid leukemia, multiple myeloma, and non-Hodgkin lymphoma.

View a graph of cancers where the causes of sex differences are unknown.

Thyroid cancer was the only type of the 13 that disproportionately affects women. In fact, for thyroid cancer, sex is the strongest known determinant. Researchers have postulated a link with female sex hormones to explain this disparity, but the evidence is contradictory so there is no consensus on the matter.

“While the sex disparity for most of these cancers is fairly well-known, no one has really taken a holistic view of this topic before,” Edgren said. “Both within science and outside, I’ve yet to come across anyone who is aware of just how large these differences are. Here we show that cancer is first and foremost a disease of men.”

Further research is needed to determine the causes of the significant sex disparities in cancer rates, said Edgren, adding that he believes the new research “can serve to guide researchers in fruitful directions.”

–Karen Feldscher

photo: Rupak de Chowdhuri/REUTERS