During a median follow-up time of 7.5 years, a total of 165 small intestinal cancers were diagnosed (111 male cases and 54 female cases). The cases comprised of 60 adenocarcinomas (45 male and 15 female) and 80 carcinoid tumors (50 male and 30 female); the remaining 25 cases were excluded from this analysis since they were a mixture of histologically not otherwise specified (n = 13), sarcomas (n = 10), one mesothelioma and one nerve sheath tumor. Regarding sub-sites within the small intestine, adenocarcinomas occurred most frequently in the duodenum and jejunum, and carcinoid tumors were mainly located in the ileum.
In general, individuals in the highest tertile of red meat or saturated fat intake were more likely to be white, to be current smokers, and to have a higher BMI and energy intake than those in the lowest tertile. In contrast, those in the highest tertile of red meat or saturated fat tended to be less educated and less likely to consume fruits, vegetables and alcohol than those in the lowest tertile ().
Means and proportions for baseline characteristics of the NIH-AARP Diet and Health Study cohort (n = 494,000) by tertiles of red meat and saturated fat
Although the HRs were elevated for red meat and the risk of both adenocarcinomas and carcinoids, the confidence intervals were very wide and not statistically significant (). With regard to processed meat, there was no association for either adenocarcinoma or carcinoids of the small intestine. Furthermore, splitting processed meats into those derived from red or white meats did not reveal any associations for small intestinal cancer (data not shown).
Multivariable† hazard ratios and 95% confidence intervals (both genders combined) for small intestinal cancer in the NIH-AARP Diet and Health Study
The energy-adjusted correlation between red meat and total fat (r = 0.50) was essentially the same as the correlation between red meat and saturated fat (r = 0.49). Individuals in the highest, compared with the lowest tertile of total fat intake had an elevated risk of carcinoid tumors of the small intestine (HR = 2.16, 95% CI: 1.10–4.25; Ptrend = 0.03), and a suggestion of an elevated risk in the continuous data (HR = 1.32, 95% CI: 0.96–1.82, per 10 gram increase) ().
An investigation by sub-groups of fat revealed that individuals in the highest, compared with those in the lowest, tertile of saturated fat intake had an increased risk of carcinoid tumors of the small intestine (HR = 3.18, 95% CI: 1.62–6.25; Ptrend = 0.0008); this risk was also evident in the continuous data (HR = 3.72, 95% CI: 1.79–7.74) (). Although the HR for adenocarcinoma of the small intestine was elevated for the top tertile of saturated fat intake, the risk was not statistically significant. However, the risk difference for saturated fat intake between the two histologic sub-types was not statistically significant (Pheterogeneity = 0.29). Neither monounsaturated nor polyunsaturated fat intakes were statistically significantly associated with small intestinal cancer, although the HRs for adenocarcinoma were elevated for polyunsaturated fat intake in both the second and third tertiles.
Although we had limited statistical power, we were able to examine the association between the major food groups contributing to total fat intake and small intestinal cancer on the continuous scale (per 10 gram increase). The risk for carcinoid tumors was the highest for fat from dairy products (HR = 3.64, 95% CI: 1.94–6.83; Ptrend <0.0001), and was also elevated, but not statistically significant, for fat from red meat (HR = 1.65, 95% CI: 0.83–3.28; Ptrend = 0.16).
In a lag analyses of the continuous data, the positive association for saturated fat intake and carcinoid tumors of the small intestinal cancer remained if we excluded the first year of follow-up (n = 72 cases: HR = 3.69, 95% CI: 1.70–7.99) or the first two years (n = 65 cases: HR = 3.36, 95% CI: 1.47–7.68). The variables confounding the fat association the most were smoking and fruit intake. The interaction analyses of saturated fat with smoking (Pinteraction = 0.80) and fruit (Pinteraction = 0.45) were not statistically significant.
In a sensitivity analysis, we additionally adjusted the multivariable saturated fat model for red meat intake. The risks for carcinoid tumors for those in the highest, compared to the lowest, tertile of saturated fat remained (HR = 3.27, 95% CI: 1.60–6.67; Ptrend < 0.001). Furthermore, using residual energy adjustment did not change the risk estimates for carcinoid tumors and intake of red meat (HR for the third versus first tertile = 1.46, 95% CI: 0.78–2.71; Ptrend = 0.36) or saturated fat (HR = 3.04, 95% CI: 1.59–5.83; Ptrend = 0.0006).
We conducted an exploratory analysis by gender, but only in the continuous data due to small case numbers. The risk of carcinoid tumors was elevated in both women (HR = 3.83, 95% CI: 1.23–12.0; Ptrend = 0.02) and men (HR = 3.56, 95% CI: 1.35–9.38; Ptrend = 0.01) per 10 gram increase in saturated fat. There were too few small intestinal adenocarcinomas in women (n = 15) to report on this histologic sub-type by gender.
There were an additional 13 cases of carcinoid tumors and 4 cases of adenocarcinoma of the small intestine that occurred after a separate diagnosis of cancer at a different site during follow-up. These cases were excluded from our primary analysis because the presence of the first cancer may have prompted a dietary change, which may mask any associations between diet and small intestinal cancer. When we included these cases in a sensitivity analysis, the positive association for saturated fat intake and carcinoid tumors remained (n = 93; HR = 2.59, 95% CI: 1.39–4.84; Ptrend = 0.003 for the third versus first tertile; HR = 2.64, 95% CI: 1.31–5.29 for the continuous data).