**3. Association between Nuts and Cancer**

Nutrition was demonstrated to have a causal and protective role in the progress of several types of cancer, the second leading cause of death worldwide [90].

A number of studies published in the last ten years have demonstrated the influence of nut consumption on cancer [91–107] (Table 5). Despite the fact that, in the observational studies, no causality could be proven, there were still several obvious strengths: prospective design for the majority of the studies, large population size, high retention rates with long-term follow-up, and adjustments for a multitude of other potential risk factors.

**Table 5.** Association between nut consumption and cancer.





receptor negative; F—women;

Health; OR—odds ratio;

HPFS—Health

PR—progesterone

 receptor;

 Professionals

 Follow-up Study; HR—hazard

RCT—randomized

 controlled trial; RR—relative

 ratio; M—men; n-6—omega 6;

 risk.

NHS—Nurses'

 Health Study;

NIH—National

 Institutes of

Several studies indicated that patients in the highest tree nut and peanut-intake group compared to the lowest intake group at any point in time during the study period were: 40%, 25%, and 14% less likely to die from total cancer, gastric noncardia adenocarcinoma, and lung cancer, respectively [16,97,98]. Also, they were 46%, 45%, and 47% less likely to die from esophageal squamous cell carcinoma, estrogen receptor negative breast cancer, and estrogen-progesterone receptor breast cancer, respectively [100,102]. Subjects having at least two servings of nuts per week had 0.68 times the risk of pancreatic cancer compared with subjects having nuts never or almost never [93]. The oil extracted from walnuts exhibited in vitro ability to reduce the viability of esophageal cancer cells, induced necrosis and cell cycle arrest, and displayed anticarcinogenic effect, thus it may present favorable effects in esophageal cancer in humans [108].

A recent prospective study showed that nut intake was not strongly associated with hepatocellular carcinoma but a significant inverse association with tree nut consumption was noted [106]. Higher intake of tree nuts and peanuts, but not peanut butter, was associated with a significantly reduced risk for small cell carcinoma (lung cancer subtype), after adjusting for smoking frequency and duration, and a non-significant decrease in lung cancer risk for men, results which have not been replicated in women [107].

The following case control studies also reported inverse associations between nut consumption and different types of cancer. In the highest intake group the outcomes were 57% and 28% less likely for prostate cancer and ovarian cancer, respectively [91,92]. Similarly, peanut consumption was linked with a lower risk of esophageal squamous cell carcinoma [103]. Lee et al. [104] noticed that odd ratios were 70% less likely for colorectal cancer in women and men, 60% (in women) and 77% (in men) less likely for rectal cancer, and 87% (in women) and 61% (in men) less likely for distal colon cancer, for the highest nut-intake group. Also, the results from a very recently published study suggest that, particularly among women, moderate to high nut intakes (2 to 5.5 servings/week) may be associated with a lower risk of colorectal adenomas, the precursor to most colorectal cancers [109]. Yang et al. [95] showed that the colorectal cancer risk for women who consumed tree nuts and peanuts ≥2 times per week was 13% lower compared to non-consumers, with a borderline statistical significance (*p*-trend = 0.06). Fadelu et al. [101] proved that higher total nut intake was linked with a significantly reduced incidence of cancer relapse and death in subjects with stage III colon cancer, but the benefit was limited to tree nut consumption.

These results confirm those of Casari and Falasca [110], who linked nut intake with a positive effect against cancer, and Aune et al. [22], who noticed a 15% decreased cancer risk in subjects eating 28 g of nuts daily compared to subjects who did not have nuts.

A new clinical trial showed that walnuts could alter tumor gene expression in women with confirmed breast cancer in ways expected to decrease cancer growth, delay proliferation, reduce metastasis, and increase cancer cell death [105]. Toledo et al. [111] indicated also that walnut-enriched diets could modulate breast cancer growth. These results are in accordance with those reported by Soriano-Hernandez et al. [112] where, in the group that consumed higher amounts of walnuts, almonds and peanuts, the breast cancer risk was between 55 and 67% less likely.

Higher nut consumption might influence cancer risk through its association with lower circulating levels of total cholesterol, CRP, IL-6, and insulin. Different compounds, such as flavonoids from nuts or their by-products might lower the risk of head and neck cancer [113] and could present chemopreventive properties and anticancer potential [114–116]. These bioactive antioxidant molecules can act alone or most likely in synergism to regulate the inflammatory response and immunological activity, prevent the development of prostaglandins or pro-inflammatory cytokines, and potentially inhibit cancer risk.
