Obesity and Cancer: Pursuing Precision Public Health
Today, nearly 40% of adults and 20% of children are obese, and those percentages are increasing. By 2030, researchers project that obesity will affect nearly half of US adults. Without intervention, the obesity epidemic will result in more cancers. Obesity is a disease that affects all aspects of the cancer continuum, including cancer risk, cancer detection and diagnosis, response to cancer treatment, and survivorship. Not only is obesity associated with a higher risk of 13 types of cancer, it is also associated with poorer survival rates for several types of cancer, including leukemia, breast, colon, and prostate.
NCI is addressing this public health crisis in several ways. The institute funds research to understand the molecular and physiological mechanisms that explain the associations between obesity and cancer risk, treatment response, and recurrence. NCI-funded researchers are also focused on understanding how behaviors such as physical activity, diet, and sleep—and their associated psychological, social, and biological underpinnings—affect obesity.
Obesity increases the risk of other diseases, including cardiovascular disease and diabetes, while intentional weight loss has been shown to reverse some obesity-associated disease risks. For example, people who have had bariatric surgery have a reduced risk of breast, colon, endometrial, and pancreatic cancers compared with their obese peers who did not undergo bariatric surgery. Taking a multifaceted approach to address the highly complex challenges that obesity presents is essential. This includes NCI collaborating with other NIH institutes and centers to facilitate research opportunities to enhance our understanding of obesity.
In addition, the COVID-19 pandemic has created new challenges. For example, there is a need to understand the complex interplay between obesity and immune responses to infectious diseases, such as COVID-19. That interplay creates a potential risk of severe complications for patients with obesity and cancer. Another concern is the conditions created by the pandemic that may promote weight gain, such as stress and isolation.
More research is needed to fully understand how obesity affects cancer risk, progression, and treatment and to develop more precise strategies to prevent obesity and promote weight loss to reduce cancer risk and improve survivorship. As researchers identify the metabolic and behavioral factors that link obesity and cancer, it may be possible in the future to target interventions to reduce an individual’s cancer risk or improve outcomes for patients. For example, emerging evidence suggests that metformin, which is commonly used to treat diabetes, may also exert chemopreventive and antitumor effects in some cancers.
Uncovering the Biology at the Intersection of Obesity and Cancer
Obesity is linked to changes in metabolism, hormone signaling, inflammation, and microbiome function—all of which influence cancer risk, response to treatment, and recurrence through mechanisms that are still being investigated. Unraveling causal relationships is necessary to understand why obesity predisposes people to certain cancers, and to develop interventions based on these molecular mechanisms.
For example, obesity is associated with an increased risk for pancreatic cancer. Multiple mechanisms are attributed to obesity’s role in pancreatic tumor initiation, progression, and metastasis. One of those mechanisms is chronic low-grade inflammation. Chronic inflammation can cause DNA damage and inhibit DNA repair, leading to a higher rate of mutations. Chronic inflammation can also create an immune-suppressed environment conducive to cancer cell growth.
In addition, obesity can increase the risk of type 2 diabetes, which is also associated with an increased risk for pancreatic cancer. Researchers have identified many overlapping and distinct mechanisms of diabetes and obesity that also drive pancreatic cancer. NCI is currently supporting several initiatives to better understand the link between pancreatic cancer and diabetes.
Addressing the Challenge of Childhood Obesity
Childhood obesity rates have been steadily increasing over the last several decades. NCI collaborates with other federal and nonfederal partners to support research and interventions to address childhood obesity, which raises the risk of cancer and metabolic conditions and complicates the care of patients with cancer. One example is the National Collaborative on Childhood Obesity Research.
As many as one in three pediatric patients with newly diagnosed acute lymphoblastic leukemia (ALL) is overweight or obese, and pediatric obesity has been shown to have an adverse impact on ALL relapse and survival. Ongoing research is focused on identifying the underlying biological mechanisms to explain why. NCI-funded researchers are also investigating both medical and behavioral interventions to improve outcomes in overweight and obese children with cancer.
Understanding the Link between Obesity and Early-Onset Cancers
Research, including studies supported by NCI, suggests that obesity early in life may also increase the risk of developing certain cancers at an earlier age. For example, colorectal cancer incidence and mortality are increasing among people below the age of 50, and research suggests that obesity may be one of the contributing factors.
NCI-funded scientists at the Washington University School of Medicine, Harvard University, and their collaborators reported in 2019 that a high body mass index in early adulthood was associated with a risk of early-onset colorectal cancer among women participating in the Nurses’ Health Study II. More research needs to be done to understand how weight and other factors, including biological and environmental, contribute to early-onset cancers.
Treating Patients with Obesity and Cancer
Obesity affects cell metabolism throughout the body and may enhance or reduce the effectiveness of cancer treatment. As just one example, NCI-funded research has shown that fat cells can sequester and metabolize the chemotherapy drug daunorubicin (Cerubidine), thus reducing its effectiveness on tumor cells. In this way, the chemotherapy is less effective in patients with obesity, even when the dose is adjusted for body weight.
In contrast to chemotherapy, preliminary evidence suggests that obesity is associated with a better outcome among patients with cancer treated with immunotherapy, although the effect is still not well-understood. Obesity can also alter the composition and activity of the microbiome throughout the body, which affects the immune system. Much more research is needed to tease out the interactions between obesity and cancer treatments to inform patient care.
Developing Behavioral Strategies for Weight Loss to Reduce Cancer Risk and Improve Patient Outcomes
Research to develop and test individual and community-based behavioral interventions for weight loss will help improve health overall as well as prevent cancers and improve cancer outcomes in patients and survivors. The goal is to develop precise behavioral interventions—that include components involving diet and physical activity—so that individuals can not only achieve the difficult goal of losing weight, but also sustain that loss over time.
Testing the Impact of Weight Loss on Survivors of Cancer
Studies evaluating the impact of returning to a normal body weight from an obese state suggest that weight loss may decrease rates of cancer recurrence in patients with breast and prostate cancers, but additional clinical trials are needed to confirm these findings. To that end, NCI is funding a large phase 3 trial to test whether a weight loss intervention can reduce recurrence and prolong survival among breast cancer patients and survivors.
Another NCI-funded clinical trial is evaluating the impact of a weight loss intervention on overweight and obese men with localized prostate cancer under active surveillance. The goal of this trial is to evaluate whether weight loss improves health-related quality of life and prostate cancer progression.
Tailoring Weight Loss Interventions to Reduce Cancer Disparities
Cancer risk is greater for non-Hispanic Black adults compared with Hispanic or non-Hispanic White adults. Obesity may be one contributing factor, as the prevalence of obesity is highest among non-Hispanic Black adults (38.6%) compared with Hispanic adults (32.6%) and non-Hispanic Whites (28.6%). Disparities in obesity and cancer risk also exist between rural and urban populations. The prevalence of obesity is significantly higher among adults living in rural areas than among those living in metropolitan areas.
NCI supports research to understand the reasons for these disparities and to develop new strategies to address them. This includes research on environmental factors that contribute to obesity, including food and transportation systems and human-made parts of the environment where people live and work (for example, homes, buildings, sidewalks, and recreational spaces).
Addressing inequities in obesity among racial and ethnic minority populations has proven to be challenging. Factors that contribute to health disparities are embedded at the individual, interpersonal, community, and societal levels. The complex and dynamic interplay of these multiple levels of influence perpetuate health inequities. NCI funds research that elucidates the various causes of obesity and cancer disparities so that all populations benefit from scientific advancements to improve health. Just one example of NCI-funded research in this area is the adaptation of effective weight loss interventions, including dietary and physical activity strategies, in a culturally relevant manner for cancer survivors from diverse racial and ethnic groups.
Understanding Factors Contributing to Weight Loss Maintenance
With NCI’s support, researchers have developed effective strategies to initiate weight loss, but maintaining weight loss over time remains a challenge. Individuals differ greatly in their ability to maintain weight loss. NCI, in collaboration with the National Heart, Lung, and Blood Institute, is supporting efforts to understand the precise biological, psychological, social, and environmental influences that contribute to successful and sustained weight loss.
Adding to the complexity, evidence suggests that many genes, gene variants, and mechanisms that regulate gene expression contribute to varied responses to weight loss interventions. Genome-wide association studies (GWAS) have implicated genes from several biological pathways in obesity. These studies have revealed genes involved in pathways influencing appetite and satiety regulation, insulin secretion and function, formation of fat cells, and energy metabolism that contribute to obesity, variation in body mass index, and weight maintenance. More research is needed to understand the biology of these obesity-associated genes. NCI supports research to understand the complex interplay of genetics and behaviors and to identify genetic predictors of treatment response to behavioral weight loss interventions.
Improving the Measurement of Health Behaviors
NCI researchers are working collaboratively to develop better methods to precisely measure patterns of physical activity, diet, and sleep that, until now, have been studied in silos. The sophistication and wide-spread use of digital devices, such as smart watches, to monitor sleep and activity patterns continuously has made it easier for researchers to study 24-hour behavioral patterns. Smart phone apps have expanded the capacity to track dietary intake on a 24-hour basis more accurately and inexpensively. When combined, such technologies expand data quality and accuracy, which is essential to understand how behavioral patterns may influence obesity and overall cancer risk.