Charles S. Fuchs
Diets with higher nut consumption appeared to be associated with reduced risk for disease recurrence and mortality among patients with stage III colon cancer, according to results from the prospective, observational CALGB 89803 study.
Observational studies have suggested diet and lifestyle factors — such as type 2 diabetes, obesity, sedentary lifestyle, Western-pattern diet, increased dietary glycemic load and high intake of sugar-sweetened beverages — are associated with risk for colon cancer recurrence and death. Although nut intake is associated with lower risk for type 2 diabetes, metabolic syndrome and insulin resistance, whether nut consumption had an effect of colon cancer recurrence and survival had not been known.
“These studies support the hypothesis that behaviors that make you less insulin resistant, including eating nuts, seem to improve outcomes in colon cancer,” Charles S. Fuchs, MD, MPH, director of the Yale Cancer Center, said in a press release. “However, we don’t know yet what exactly about nuts is beneficial.”
Fuchs and colleagues evaluated data from 826 patients with stage III colon cancer who reported dietary intake on a food frequency questionnaire while enrolled in a randomized trial of adjuvant chemotherapy.
During a median 6.5 years of follow-up, 199 patients experienced recurrence or developed new primary tumors and 177 patients died, 39 of whom died without documented cancer recurrence.
Researchers considered nut consumption levels as never (n = 145; median age, 64 years), less than one serving per month (n = 98; median age, 60 years), one to three servings per month (n = 211; median age, 58 years), one serving per week (n = 214; median age, 59 years), or two or more servings per week (n = 158; median age, 62 years).
Compared with patients who did not eat nuts, those in the highest category of consumption demonstrated improved DFS (HR = 0.58; 95% CI, 0.37-0.92) and OS (HR = 0.43; 95% CI, 0.25-0.74), with a trend toward improved RFS (HR = 0.7; 95% CI, 0.42-1.16).
Subgroup analyses showed the improvement was confined to consumption of tree nuts — which include almonds, walnuts, hazelnuts, cashews and pecans — for DFS (HR = 0.54; 95% CI, 0.34-0.85) and OS (HR = 0.47; 95% CI, 0.27-0.82).
Researchers found no association between the consumption of peanut butter and improved outcomes.
The association of total nut intake on improved outcomes persisted in analyses that considered other known colon cancer recurrence risk factors.
Patients may be wary of nut consumption due to their greater fat content, according to the researchers.
“People ask me if increasing nut consumption will lead to obesity, which leads to worse outcomes,” Fuchs said. “But, what’s really interesting is that in our studies, and across the scientific literature in general, regular consumers of nuts tend to be leaner.”
Researchers noted the study may be limited by the self-reported nut intake and measurement error. Also, although the findings further support the role of diet and lifestyle as modifiable risk factors for colon cancer, the observation study does not support causality.
“Overall, we are working to apply the same rigorous science to the understanding of diet and lifestyles in the colon cancer patient population that we apply to defining new drugs,” Fuchs said. – by Alexandra Todak
Disclosures: Fuchs reports leadership role with CytomXTherapuetics, and consultant/advisory roles with Agios, Eli Lilly, Entrinisic Health, Five Prime Therapeutics, Genentech, Gilead Sciences, KEW Group, Merck, Merrimack and Taiho Pharmaceutical.
Wafik S. El-Deiry
Patients with stage III colon cancer want to know what more can they do to reduce the chance the tumor will recur or to improve their chances of being cured. There is, of course, much that is known about diet and lifestyle factors that influence colon cancer incidence, recurrence and mortality. Diabetes, obesity, the Western diet, sugary drinks and sedentary lifestyle increase the chance of colon cancer recurrence and death. Nut intake lowers mortality from cardiovascular disease, and lowers risk for type 2 diabetes, but the effect of nut intake on colon cancer recurrence and death was unknown until this new study.
To set the stage for the nut consumption study, it is important to explain that CALGB 89803 was a phase 3 study by Saltz and colleagues — published in 2007 in Journal of Clinical Oncology — that compared weekly 5-FU to weekly 5-FU plus irinotecan for stage III colon cancer. The study showed the irinotecan chemotherapy added no benefit and only contributed to toxicity in the adjuvant setting — which is different from what has been observed in metastatic disease, where irinotecan adds benefit. But, how can outcomes be improved for patients with colon cancer? Patients want to know, and CALGB 89803 provided an opportunity to query lifestyle and dietary factors vs. outcomes.
The nut consumption study involved conducting comprehensive dietary and lifestyle surveys while patients enrolled in CALGB 89803 were receiving chemotherapy and at 6 months after completion of chemotherapy. Researchers pooled data from 826 evaluable patients — those who completed adjuvant therapy and the two required surveys — from the two chemotherapy treatment arms. The authors found that nut intake after colon cancer diagnosis appeared associated with significant improvement in DFS and OS. The results are impressive in the magnitude of improved survival — a 42% improvement in DFS and a 57% improvement in OS.
The association between nut consumption and improved outcome for treated stage III colon cancer was limited to tree nuts — walnuts, almonds, cashews, pecans and hazelnuts, among others — but not peanuts, known as ground nuts, or peanut butter. Importantly, the tree nut consumption benefit in treated stage III colon cancer was seen in the different genetic subtypes (KRAS mutated, BRAF mutated, PIK3CA mutated, or microsatellite instability high), and appeared independent of BMI or age. The greatest DFS/OS benefit occurred with the greatest nut consumption.
It is important to note that the nut consumption study makes no conclusions about rectal cancer or stage IV colon cancer; these will need to be studied in the future. There may be some clues for the mechanism by which tree nuts lower risk for disease recurrence or improve OS. It is known, for example, that nut consumption is associated with lower insulin resistance, so glucose levels that are available for cancer cells potentially may be lower, or perhaps the tumor growth promoting effects of excessive insulin levels might be involved or effects on tumor cell metabolism. This is still conjecture at this point and future prospective human studies — as well as preclinical studies — will need to evaluate the underlying molecular mechanisms associated with tree nut consumption and reduced risk for stage III colon cancer recurrence. In this regard, modern day capabilities with organoid culture and blood cytokine analysis might be built into studies to assess in vivo or ex vivo changes that may be attributed to the tree nut consumption effect.
For patients, knowing about the newly published results provides a simple intervention — enjoyable for most if not all — that may make a difference to reduce the chance the stage III colon tumor may return. A good nutrition counseling program can help with incorporating the information on tree nuts along with other dietary interventions.
Saltz LB, et al. J Clin Oncol. 2007;doi:10.1200/JCO.2007.11.2144.