Why does cancer affect men and women differently?
Men and women are different in many ways, from the organs in their bodies to the emotions they wear on their sleeves, even in how they approach an argument or take on a task. So it may come as little surprise that cancer—a disease influenced by genetics, biology and lifestyle habits—affects men and women differently, too. The question that still stumps scientists is: Why?
Historically, men are more likely to get cancer and women are more likely to survive it. The evidence is backed by numerous statistics—chief among them the American Cancer Society’s (ACS) estimate that nearly one in two men will be diagnosed with cancer in his lifetime, compared with one in three women. While the statistics are straightforward, the causes behind the disparity have been harder to explain. “Some things affect gender differently,” says Dr. Ricardo Alvarez, Director of Cancer Research and Breast Medical Oncologist at our hospital near Atlanta. “We know that. What can we do with that, though?” Several studies in the past few years have identified some promising leads that may one day answer that question.
A history of difference
Scientific studies have long highlighted the discrepancy between cancer rates among men and women. A 2011 study published in the journal Cancer Epidemiology, Biomarkers & Prevention, for instance, examined data collected from 1977 to 2006 by cancer registries across the United States, concluding that women have much higher survival rates when diagnosed with the most common forms of cancers affecting both sexes, such as lung cancer and colorectal cancer, largely because men are diagnosed with cancer more often in the first place.
The study suggested that the differences between the sexes in part comes down to carcinogenic exposures and lifestyle factors, such as smoking cigarettes, drinking alcohol and eating fattier foods—all of which typically are more prevalent among men, says Dr. Glen Weiss, Director of Clinical Research and Phase I & II Clinical Trials and Medical Oncologist at our hospital near Phoenix. Other universal factors also appear to be at play, including how well the body can protect itself from damage caused by free radicals (or harmful molecules that come from the body’s normal processes or through pollutants), as well as metabolism, hormones and immune function. But the study concluded that those risk factors only tell part of the story.
Using gender to guide treatment
Earlier this year, a Cancer Cell study compared the genetics of men’s tumors with women’s and found differences in eight cancers—bladder, head and neck, thyroid, liver and two types each of lung and kidney—that suggest a gender connection. The study’s authors concluded that the findings may one day lead to targeted drugs based in part on the patient’s gender.
The study comes at a time of rapid development in the field of precision cancer treatment, which examines tumors on a molecular level, looking for genomic mutations that may be matched with drugs designed to target the abnormalities. Still, tailoring therapies or guiding treatments based on gender is premature. “We need more time to determine what to do with this information,” Dr. Alvarez says.
The Cancer Cell study raises important questions that may lead to key insights in future research, says Dr. Pamela Crilley, Chair of the Department of Medical Oncology at Cancer Treatment Centers of America® (CTCA) and Chief of Medical Oncology at our hospital in Philadelphia. “This study is extremely intriguing because it looks at issues that have long been noted but not well explained,” Dr. Crilley says. “It paves the way for further clinical trials to try to both reproduce this finding and determine how it can be used. At this time, the study does not translate into clinical practice, but with how quickly studies in precision cancer treatment are moving, we should have answers to these important questions within the next few years.”
Gender just one piece of the puzzle
Dr. Weiss says gender differences in cancer aren’t going to be explained away by tumor genomics. “Even the way individuals metabolize medication may be different,” he says. “What I don’t see in the Cancer Cell study is a description or discussion of how men and women may metabolize certain medications differently and differences in the timing of when medications are taken, or food and diet factors that may also be influential.”
As proof that other factors may be at play, Dr. Weiss points to the growing number of young women who have lung cancer who have never smoked. Overall, the number of women who have never smoked and developed lung cancer exceeds the number of male lung cancer patients who have never smoked. “That would be one of the instances where there would definitely be a gender difference, so why are women more at risk?” he says. According to the National Institutes of Health study, one of the leading causes of lung cancer in nonsmokers is exposure to radon gas. Other exposures include secondhand smoke, cancer-causing agents in the workplace, air pollution and gene mutations. “We can include the genomics of the tumor as a possible link for some targeted therapies, but the problem with a lot of these types of focused studies on genomics is that they don’t capture all the other factors,” Dr. Weiss says. “They just look at one piece of the puzzle.”
In a 2012 study published in the European Journal of Epidemiology, researchers’ conclusions echoed other studies that found that, most often, cancer affects men more often than women because of known risk factors, such as smoking and drinking. But they also found that a third of the cancers that affect one sex more than the other seem to be linked to gender alone. The study suggested that if the role gender plays could be identified—and targeted—more than a third of cancers may be prevented. But before that can happen, more research is needed, Dr. Weiss says. “I won’t say that this can’t happen,” he says. “We just don’t know enough about it at this point.”
Wherever the research leads, its benefits come only in how doctors can use the results to serve their patients. “You can have all of these data, but they’re clinically irrelevant until you can use it to help the patient,” Dr. Weiss says. “So for now, we work with what we do know.”
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