The relationship between nut intake and risk of colorectal cancer: a case control study

Total global consumption of nuts has increased 59% over the past decade [1]. Per capita consumption of seeds and nuts in the Korean population was 3.0 g/day in 1998, which increased to 7.6 g/day in 2015 [2]. The US Food and Drug Administration approved the labelling of food products containing nuts to indicate that nuts may reduce the risk of heart-related diseases.

Nuts contain many nutrients, including high quality vegetable protein, fat, unsaturated fatty acids, fiber, vitamins (e.g., vitamin E, vitamin B₆ folate, niacin), minerals (e.g., zinc, potassium, calcium, magnesium), phytochemicals (e.g., flavonoid, carotenoids, phytosterols), and other bioactive compounds [3–8]. These nutrients may reduce the risk of overall mortality [9, 10] and incidence of colorectal and endometrial cancer [11], cardiovascular diseases [12], type 2 diabetes [13, 14], and metabolic syndrome [15]. These health effects may be due to various mechanisms, including antioxidant activity [16], reduction of DNA damage [17], regulation of inflammatory response and immunological activity [18], and anti-carcinogenic effects [19].

Few epidemiologic studies have assessed the association between nut consumption and risk of colorectal cancer. Both the Nurses’ Health Study [20] and the Adventist Health Study [21] conducted in the United States suggested a null association. In the European Prospective Investigation into Cancer and Nutrition study [22], women in the highest nut and seed intake group had a significantly decreased risk of colon cancer. The results of studies examining peanut consumption and colorectal cancer risk in Taiwan [23] have suggested an inverse association for women. Several previous case-control studies have also been implemented, but results were conflicting [24–26].

The type and recipe of Korean nut intake differs from that in other countries. Nuts are mainly consumed as snacks in Korea [27]. Previous studies have grouped nuts along with peanut butter and seeds [20, 22], or had only one category for peanut products and did not consider tree nuts or seeds [23]. In addition, few studies have assessed the association of nut consumption with colorectal cancer by sub-site [20, 22]. In the current study, we investigate the relationship between nut intake and colorectal cancer risk by sub-site among Korean adults.

In sub-site analyses, among men who consumed ≥3 servings per week, a reduction in risk was observed for proximal colon cancer (OR: 0.25, 95% CI: 0.09–0.70), distal colon cancer (OR: 0.39, 95% CI: 0.19–0.80), and rectal cancer (OR: 0.23 95% CI: 0.12–0.46) compared to men who consumed none. Similarly, compared to women who did not consume nuts, women who consumed ≥3 servings per week showed an inverse association between nut consumption and risk of colorectal cancer overall, as well as distal colon cancer (OR: 0.13 95% CI: 0.04–0.48) and rectal cancer (OR: 0.40 95% CI: 0.17–0.95).

Our case-control study suggests a favorable association between high frequency of nut consumption and decreased risk of colorectal cancer among both men and women. The results of sub-site analyses showed an inverse association with all sub-sites of colorectal cancer, except for proximal colon cancer for women.

Our results are consistent with some previous studies. Findings from a meta-analysis of 3 cohort studies found a 24% decrease in the risk of colorectal cancer for the highest category of nut consumption [13]. A cohort study of women in Taiwan found that frequent peanut intake was associated with an approximately 58% reduction in the risk of colorectal cancer [23]. The European Prospective Investigation into Cancer and Nutrition study observed a null association between consumption of nuts and seeds and the risk of colorectal cancer among women. However, an inverse association was supported for colon cancer (HR: 0.69, 95% CI: 0.50–0.95 for consumption of 6.2 g/day vs. ≥0 g/day) [22]. In previous case-control studies conducted in the US [26] and Korea [30], there were no statistically significant associations between consumption of nuts and other legumes and risk of colorectal cancer. In sub-site analyses, the preventive effect was observed only for cancer in the distal colon and rectum. One of two existing studies found no statistically significant results regardless of anatomical site [20], and the other study found differences according to sub-site [22]. Clinical and molecular characteristics are different according to the anatomical location of colorectal cancer [31]. The relationship of some dietary ingredients with distal colon and rectal cancer risk was stronger than with proximal colon cancer [32]. There is a general lack of studies on the relationship between nut intake and colorectal cancer, so no clear cause for these differences is known.

Despite the similarity of our results with previous literature, there were differences in the assessment of nut consumption. First, our serving size (1 serving size = 15 g) was smaller than in studies conducted in other countries (1 serving size = 28 g). Second, in our study the only types of nuts included in the SQFFQ were pine nuts, peanuts and almonds, which may be difficult to compare with studies that included seeds, legumes, peanut butter and country-specific nuts. Third, the percentage of people who have allergies to nuts varies from country to country [33]. Previous studies have shown that people born in Asia have a relatively low risk for peanut and tree nut allergies compared to those born in Western countries [34, 35].

To explain the association between nut consumption and colorectal cancer risk, several biological pathways have been proposed. Peanuts are known to be rich in isoflavones, phytosterols, resveratrol and phenolic acid [36–38], which may have anti-cancer effects. Phytosterols, especially beta-sitosterol, have been shown both in vivo and in vitro to help normalize hyper-proliferating cells and to inhibit colon cancer [38, 39]. Resveratrol is a natural polyphenolic antioxidant, which decreases cyclins D1 and D2 and regulates the cell cycle [40]. Almonds and pine nuts contain fiber, resveratrol, selenium, flavonoids (quercetin), polyphenols (ellagic acid), and folic acid, which may prevent cancer through antioxidants, regulation of cell differentiation and proliferation, reduction of DNA damage, regulation of inflammatory response and immunological activity [17]. Each type of nut has many nutrients and phytochemicals that may be beneficial to health, and it is likely that unknown harmony effects of nuts may be related to colorectal cancer prevention. Moreover, many studies have shown a beneficial association between high nut intake and decreased risk of obesity [41–43] and type 2 diabetes [44, 45], which are risk factors for colorectal cancer.

This case-control study is the first exploration of the association between nut consumption and risk of colorectal cancer in the Korean population, where nut consumption frequency and patterns may differ compared with other countries. A number of potential limitations may influence the present study. First, we did not consider the manufacturing method (raw, roasted, or boiled) or any extra content (sugar, salt, seasoning, etc.). In Korea, most nuts are consumed in a processed form or as a garnish. Different preparation methods before and after cooking, time, and temperature conditions can affect nutrient composition and content of nuts [46, 47]. Second, we could not eliminate the possibility of some residual and unmeasured confounding. Previous studies have reported that people who consume nuts were more likely to have other healthier behaviors, such as lower intakes of alcohol and sodium, lower BMI, higher physical activity levels, better dietary quality, and higher socioeconomic status [9, 10, 48–51]. Our study had similar findings in terms of higher education, more regular exercise, and higher intakes of energy and fruits and vegetables. Thus, we adjusted for major potential confounders in our analyses. Third, the item ‘nuts’ in the SQFFQ used in this study cannot represent all nuts, because it only included peanuts, pine nuts, and almonds. For this reason, direct comparisons with the results of other studies may be difficult. Fourth, hospital controls who voluntarily participate in studies such as ours may be more likely to have a healthier lifestyle compared with cancer patients. For comparability, we recruited cases and controls in the same hospital, and adjusted for factors that were different between groups. Fifth, because of the case-control study design, recall bias is an inherent weakness. It is known that people who are conscious of health may over-report or under-report some food items [52]. However, the protective effect of nuts on colorectal cancer was not generally known at the time of the survey and thus should be unrelated to recall bias. Finally, due to the small number of participants in the highest nut consumption category, we cannot rule out the possibility that some of our results are due to chance. However, the associations were consistent in both the sub-site analyses and analyses stratified by sex, which reduces the likelihood of chance findings.

Our study had a retrospective design, which is regarded to have a lower value in terms of evidence hierarchy compared with prospective studies. Nevertheless, case-control studies can provide evidence supporting the general relationship between diet and cancer, while currently available prospective studies lack sufficient duration of follow-up for cancer occurrence. Our results do need to be confirmed in a large cohort study with an appropriate dietary assessment of nut consumption.

In conclusion, high frequency of nut consumption appears to play a role in decreasing colorectal cancer risk in this study of a Korean population. Our findings could be used to advise the general public about nut consumption.