ACS’s Michael J. Thun on Cancer: Progress, But a Long Way to Go

Science Watch Newsletter Interview: July/August 2010 (Page 1 of 3)

Michael J. ThunThe American Cancer Society (ACS) has been doing research in cancer epidemiology for over 60 years. Two huge cohort studies in particular—Cancer Prevention Study I, founded in 1959 with a million men and women in 29 states, and the CPS-II, launched in 1982, with 1.2 million Americans nationwide—have provided vitally important data, first confirming the link between smoking and lung cancer, and then helping to identify the major preventable causes of cancer in the United States.

That trend has continued as the ACS has racked up an impressive number of the most influential papers in cancer research, in the process making Michael Thun, ACS emeritus vice president of epidemiology and surveillance research, currently the #8 most-cited author in the field of Clinical Medicine as tracked in Clarivate Analytics Essential Science Indicators, based on papers published since 2000.

More recently, six of Thun’s reports published in the last two years registered as Hot Papers during 2009, just missing the threshold for inclusion in this publication’s latest annual listing of the year’s “hottest” researchers, a distinction he achieved back in 2004. In the past decade alone, Thun has co-authored nine papers that have each been cited more than 1,000 times, including articles on the relationship between overweight, obesity, and cancer mortality, as well as on particulate air pollution as a predictor of mortality in cancer. He’s also a co-author of the annual ACS review of cancer statistics, published in the society’s CA – A Cancer Journal For Clinicians; these reports routinely accumulate well over 2,000 citations for each year’s edition (see table tab at the bottom of page three).

Thun, 66, received his bachelor’s degree from Harvard College in 1970, returning to college after a three-year stint as an Army medic to complete his undergraduate degree and a post-baccalaureate program in pre-med. He received his medical degree from the University of Pennsylvania in 1975 and a master’s in epidemiology from the Harvard School of Public Health in 1983.

After working as an epidemiologist for the New Jersey State Health Department and the Centers for Disease Control in Atlanta, Thun joined the American Cancer Society in 1989 as director of its division of analytic epidemiology, and in 1997, as vice president for epidemiology and surveillance research. Last year, Thun stepped down from this position to devote his attention to full-time research.

Thun spoke to from his office in Atlanta, Georgia.

SW: Let’s first talk about your early research. In 1991, just two years after joining the ACS, you published a paper in the New England Journal of Medicine on aspirin use and reduced risk of fatal colon cancer that’s been cited over 1,000 times (M.J. Thun, et al., 325[23]: 1593-6, 1991). What prompted this research, and what did you learn?

In 1991, Lynn Rosenberg and her colleagues in Boston published a case-control study in the Journal of the National Cancer Institute (JNCI) showing lower colorectal cancer incidence in regular aspirin users. Lynn had recognized that there was extensive literature suggesting that aspirin and other NSAIDs inhibited the development of chemically induced colorectal cancers in rodents, but that line of research had simply not jumped to humans. Basically it received no attention at all until she published her case-control study.

The results from her study were intriguing but subject to the potential biases of the case-control, or retrospective, design. We were able to replicate the association prospectively in the 1.2 million CPS-II cohort. We published the results in the New England Journal of Medicine in 1991, and this drew tremendous attention to the issue of NSAIDs and cancer prevention and also the issue of chronic inflammation and cancer.

SW: How come we’re not all being told today to take a daily aspirin to reduce our cancer risk?

Well, the utility of aspirin in prophylaxis for cancer is obviously a function of whether the benefits exceed the risk. With aspirin, the principal risk is bleeding. And this risk, while relatively low, turned out to be sufficient to offset the benefits of reducing colorectal cancer incidence. So aspirin has to inhibit more than colorectal cancer incidence for potential anti-cancer effects to influence clinical recommendations for prophylactic aspirin use.

"With the aging of the population, the number of incident cancers will roughly double from 2000 to 2050 in the U.S., assuming that incidence rates remain the same," says Michael J. Thun of the American Cancer Society.

And there is some evidence that adult-strength aspirin, not baby aspirin, as we first reported in 1993, may also have a small protective effect against breast and prostate cancer and maybe other cancers as well. Eric Jacobs in our group confirmed that in a JNCI paper published in 2007. If it can be replicated in a clinical trial, it’s conceivable that the aggregate protection against several common cancers could affect the recommended dose of prophylactic aspirin use for heart disease, which is currently a baby aspirin a day.

On the other hand, a randomized trial, the Women’s Health Study—not to be confused with the Women’s Health Initiative—found no reduced risk after ten years of baby aspirin every other day.

SW: Was the Women’s Health Study result considered the end of the hypothesis?

The Women’s Health Study only proved that a very low dose of aspirin—a baby aspirin every other day—did not reduce the risk of colon cancer in women after ten years of use. This leaves open the question of whether the dose used in the study was too low, or the duration of exposure and follow-up too short. That’s where the critical questions remain.

If it can be established that aspirin at about an adult-strength dose lowers risk of all cancers combined, then it’s conceivable that this could affect the recommended dose of people taking aspirin for heart diseases, but that would require further clinical trials.

Page 1 ¦ 2 ¦ 3 [Highly Cited Papers by Michael J. Thun on page 3]

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