Obesity linked to worse outcome in patients being treated for colon cancer

It’s long been known that obesity is linked to increased risk of developing colon cancer, but now researchers at the Mayo Clinic campus in Minnesota have found that obesity is associated with worse outcomes in patients who have already been diagnosed and treated for the cancer.

The authors found that obesity was significantly associated with a greater number of tumour-containing regional lymph nodes and worse survival rates, independent of other tumour features. Their data also showed that depending on a patient’s gender, varying levels of obesity were associated with an increased risk of death ranging from 19 percent to 35 percent, compared to non-obese patients. The study is published in Clinical Cancer Research.

The researchers say their findings, culled from thousands of patients who had their colon cancer surgically removed and were enrolled in one of seven chemotherapy trials supported by the National Cancer Institute (NCI), suggest that colon cancer patients should try to maintain a body mass index (BMI) that is less than 30. A BMI less than 30 can fall into normal (20–24.9) or overweight (25–29.9) categories. A BMI 30 and higher is considered obese. A person’s BMI is the ratio between height and weight.

"We found that obesity is associated with more aggressive colon cancers, with the effect being stronger in men than in women," says the study’s lead author, Frank Sinicrope, MD, a Mayo Clinic medical oncologist. "Our data suggest that a little extra weight is okay, but body weight in the obesity range puts a patient at increased risk for cancer recurrence and spread and, based upon other studies, also would be expected to increase the risk of precancerous colon polyps and a second colon cancer."

The study population included patients participating in clinical trials conducted by Mayo Clinic and the North Central Cancer Treatment Group and a study from the Southwest Oncology Group. The researchers calculated BMI at study entry in 4,381 patients with resected stage II (lymph node negative) or stage III (node positive) colon cancers who had enrolled in one of seven randomised trials testing 5-fluorouracil-based adjuvant chemotherapy. Among these patients, 868 (20 percent) were considered obese. Within this group, 606 patients were class 1 (BMI 30–34.9) and 262 were very obese (class 2 or 3, which is a BMI of 35 or greater).

Researchers found that, overall, class 2 and 3 obesity was associated with a 19 percent increase in the risk of death, and that any class of obesity was significantly associated with an increased number of metastatic regional lymph nodes, compared to normal weight patients.

The researchers also observed differences between men and women. "There was a stronger relationship between BMI and clinical outcome in men compared to women," says Dr Sinicrope. "The greater the level of obesity in men, the higher their risk of cancer recurrence and death. In women, however, the highest risk was seen in those with class 1 obesity, compared to normal weight women."

For example, men with class 2 or 3 obesity had a 35 percent increased risk of death, compared to normal weight men, whereas women with class 2 or 3 obesity had only an 11 percent increased risk of death – a finding that was not statistically significant. However, women with class 1 obesity had a 24 percent increased risk of death.

On the other hand, men who were overweight, but not obese, had a modest 6 percent improvement in survival and underweight women had significantly worse survival rates, an association other studies have also noted.

Although the researchers say that the exact mechanisms by which obesity leads to more aggressive colon cancers remain unknown, hormones such as insulin and insulin-like growth-factor-1 (IGF-1) are associated with obesity, and higher levels have been found in patients who developed colon cancer. Regarding the observed gender differences, BMI is more closely related to abdominal fat or central obesity in men than in women and other studies have shown an association between increasing waist size and risk of colon cancer recurrence or death. In women, the situation is more complex due to the potential influence of oestrogen levels, menopausal status, and hormone replacement therapy in women, Dr Sinicrope says. "These are factors that we did not examine in this study due to lack of available data," he says.

"The association between body weight and increased risk of cancer recurrence and death is obviously complicated, and we need further studies to help clarify this relationship, but such information has the potential to help patients survive their cancer and assist physicians in caring for them," says Dr Sinicrope.

(Source: Mayo Clinic: Clinical Cancer Research: March 2010)