1. The International Agency for Research on Cancer (IARC) recently published a new evaluation of the evidence linking overweight and obesity to cancer risk. Can you provide some background and explain why the IARC reviews this evidence?
Dr. Ligibel: There is growing evidence that obese individuals are at increased risk of developing and dying from malignancy. Interest has grown in studying the relationship between body weight and cancer risk, especially after the publication of a seminal study by Calle et al published in the early 2000s in the New England Journal of Medicine (NEJM) that followed a large cohort of Americans for about 20 years and demonstrated that the heaviest members of the cohort had a significantly increased risk of developing and dying from cancer as compared with normal weight individuals. Over time, the evidence linking obesity to cancer risk and cancer outcomes has grown. In 2002, the IARC initially summarized the observational data linking obesity and cancer risk and graded the strength of the evidence to determine if it was sufficient to declare a consistent relationship between obesity and cancer risk for a number of different malignancies.
2. What, if anything, makes obesity a tricky subject to examine as far as its connection with many diseases, but with cancer specifically?
Dr. Ligibel: The data that link obesity to cancer risk come from a number of different types of studies, including case-control studies in which people are evaluated after they develop malignancy and are matched with similar individuals in the community to determine whether there is an association between body weight and cancer risk, and large prospective cohort studies that look at the relationship between body weight over time and the incidence of malignancy. Since the last IARC report, we have seen stronger evidence emerge from these studies that supports the relationship between obesity and cancer risk. One of the complicated aspects of studying the relationship between obesity and disease is that we typically define obesity based on body mass index (BMI), which is a normalized measure that takes into consideration an individual’s height and weight. We recognize that people can have different body compositions at different BMIs. There are some individuals who, although they have a high BMI, may have a higher proportion of muscle or they may have less of the types of body fat that we think leads to increased cancer risk, specifically visceral adiposity or excess weight in the visceral area of the body, rather than subcutaneous fat. One of the things that makes this area difficult to study is that our common measures provide us with a relatively limited view of what is happening at an individual level from a metabolic standpoint. There may be people who are heavier, but who are also metabolically healthy, and there are individuals who are leaner with a high proportion of body fat. That is one of the shortcomings of the evidence that we have linking obesity to cancer, as well as other diseases.
3. In 2002 when the IARC evaluation was published, the group concluded that there was a link between obesity and certain cancers. Can you discuss what was found then and what the most recent review published in NEJM has updated?
Dr. Ligibel: In 2002, the IARC review evaluated the existing data evaluating the relationship between obesity and cancer risk. At that point there were already hundreds of case-control and cohort studies looking at this relationship. The 2002 IARC working group determined that there was sufficient evidence linking obesity to the risk of developing a number of malignancies, including postmenopausal breast cancer, endometrial cancer, and some gastrointestinal cancers. In 2016, when this evaluation was repeated, the number of studies had grown exponentially, almost to the point where it was very difficult to even summarize all of the data linking obesity to malignancy. The list of malignancies for which the strength of evidence in humans was felt to be significant was expanded to include a number of additional malignancies, such as multiple myeloma and pancreatic cancer. In other malignancies, such as prostate cancer, the evidence is still emerging. Finally, an inverse relationship was found between obesity and cancer in some malignancies, especially in cancers where smoking is a causative factor.
4. Based on the evidence available today, what should clinicians do to adjust their practice?
Dr. Ligibel: The data that link obesity to cancer risk are primarily observational. There are no trials, at this point, that have looked at the impact of weight loss interventions on cancer risk. There are some very interesting data emerging that demonstrate that patients with higher levels of obesity who undergo bariatric surgery have a dramatic decrease in risk for developing cancer in subsequent years. However, these data are not from randomized trials, but rather observational studies that provide some of the first proof that weight loss can be an effective way of potentially avoiding malignancy. As clinicians, recognizing the increased risk of malignancy imparted by obesity is important. When counseling an obese patient about health risks, clinicians should not only consider risk of cardiovascular disease or diabetes, but also the risk of cancer.