Obesity has been linked to a poorer prognosis for several common cancers, including those of the breast, colon, and esophagus. However, the impact of obesity on cancers of the head and neck has been unclear. Research has provided conflicting results, with some studies suggesting low body weight diminishes a patient’s chance of survival for certain cancers, while other studies were inconclusive.
Now, researchers at Memorial Sloan-Kettering and Weill Cornell Medical College have made a striking discovery about one head and neck cancer in which obesity was previously not thought to be a factor in survival. The research team found that obesity just before diagnosis is associated with a five-fold increase in the risk of death from early-stage squamous cell carcinoma (SCC) of the tongue.
The finding, the first to associate obesity with poorer survival in any head and neck cancer, was reported online January 21 in the journal Cancer.
“This is an important step toward identifying new and relevant prognostic factors for this disease and could lead to more-effective treatment strategies,” says Neil Iyengar, a medical oncology and hematology fellow at Memorial Sloan-Kettering and the study’s first author.
Access to Samples Allows Narrow Focus
Dr. Iyengar says one reason it has been difficult to establish the effect of obesity on head and neck cancers is that past studies were not sufficiently focused.
“Most prior studies investigating interactions between body mass index and head and neck cancers included multiple tumor sites — tongue, floor of mouth, and tonsil — and multiple stages of disease,” he explains. “In addition, many patients have weight fluctuations right around diagnosis, either from the cancer or associated habits like tobacco and alcohol use. All these confounding factors have made it difficult to clearly understand the effect of obesity.”
Limiting the analysis to early-stage tongue cancer tumors filtered out some of the confounding factors that had hampered earlier research. While later-stage tongue cancer often causes weight loss just prior to diagnosis — often because the tumor obstructs or interferes with swallowing — early-stage tumors less commonly have this effect.
The researchers analyzed clinical data from 155 Memorial Sloan-Kettering patients with early- stage SCC of the tongue. “Even with a narrowly defined subset of tumors, we had access to enough patients to make these associations,” Dr. Iyengar says. “At Memorial Sloan-Kettering, we treat more patients with oral tongue tumors than most institutions in the world.”
The researchers looked at the relationship between a patient’s body mass index, a measurement of body fat based on height and weight, and how long they survived following surgery to remove the tumor. The study revealed that obese patients were significantly less likely to survive over the next few years compared with non-obese patients. At the three-year mark, 68 percent of obese patients were alive, compared with 87 percent of patients with normal weight.
Inflammation May Be the Key
It remains unclear exactly how obesity may hamper survival for this cancer. A possible clue to the biological process was provided by a 2011 study, conducted by many of the same researchers, reporting that obesity caused low-grade, chronic inflammation within the white adipose (fat) tissue of breasts. This inflammation boosted levels of aromatase, an enzyme known to help fuel breast cancer growth by increasing the production of estrogen at that site.
“When a fat cell dies, it leads to local inflammation in the area,” explains Andrew Dannenberg, Professor of Medicine at Weill Cornell Medical College, the study’s senior author, and a consultant at Memorial Sloan-Kettering. “Obese patients, with larger fat cells, are more likely to be inflamed, which could be promoting the cancer.”
Once this link was found between inflammation and the mechanisms that lead to breast cancer, it raised the possibility that the same process was taking place at other sites. The tongue became a candidate for study because it contains fat cells; the amount of fat in the tongue increases in obese patients.
“Now that we’ve associated obesity with poor survival in tongue cancer, we’re investigating whether inflammation has a role there as well,” Dr. Iyengar says. “This research is still in early stages but if such a connection is confirmed, it may open up the possibility of using antiinflammatory treatments or other targeted agents to improve outcomes in these patients.”
Apart from medications, Dr. Iyengar says there is ongoing research in many cancers into whether weight loss through increased exercise, caloric restriction, or both could break the link between obesity and poor outcomes. Early research has been promising in breast cancer patients, and the same might apply to tongue cancer.
He also said the researchers are looking into developing noninvasive techniques, such as a blood test, for detecting low-grade inflammation of the fat.
Other Memorial Sloan-Kettering co-authors on the Cancer study include medical oncologist Clifford Hudis, Chief of the Breast Cancer Medicine Service; David Pfister, Chief of the Head and Neck Cancer Service; head and neck surgeons Snehal Patel, Luc G. Morris, Jay O. Boyle, and Alejandro Pino; head and neck pathologist Ronald Ghossein; and medical oncologists Mathew G. Fury and Patrick G. Morris.
This research was supported by the National Institutes of Health (NIH) under awards UL1TR000457, UL1RR024996, and NIDCD T32 000027.