Does diet impact the risk of non-Hodgkin lymphoma?
Authors: Marta Lewandowska, Dagfinn Aune, Doug Bristor, Shireen Kassam. Published in www.ijdrp.org VOL. 1, NO. 1. 2019
Non-Hodgkin lymphoma (NHL) is the eleventh commonest cancer globally and the sixth and eighth commonest in the United States and United Kingdom, respectively1. There are established risk factors, including viral infections, autoimmune disease, occupational exposures, and radiation, but the vast majority of cases remain unexplained. A frequent question asked by patients is “What about my diet?” For certain cancer types, there are well-established associations between dietary exposures and diseases, such as processed meat and bowel cancer. However, for NHL the associations with dietary factors are less established and often not considered in consultations. Given that some common NHL subtypes have a familial risk, there may be an opportunity to counsel family members on lifestyle approaches aimed at risk reduction.
With this in mind, we review evidence for the relationship between diet and the risk of NHL. The data are summarised in Table 1.
We conducted a literature search using PubMed to identify relevant available articles published in English. Search terms included meat, processed meat, dairy, fruit, vegetables, or organic, and non-Hodgkin lymphoma, NHL, or lymphoma. We focused on meta-analyses when available, but included single studies when no meta-analysis was available (ie, organic food).
A meta-analysis of red and processed meat consumption and risk of NHL (20 articles, 15 189 cases) reported a summary relative risk (RR) of 1.32 (95% CI, 1.12–1.55) for red meat and 1.17 (95% CI, 1.07–1.29) for processed meat.2 The association was only significant for case-control studies (n = 16), but not for the cohort studies (n = 4), which suggests the results may be subject to recall and selection bias. Further cohort studies are needed given the limited number of published studies.
Another meta-analysis studied all foods of animal origin and the risk of NHL.3 Based on 10 149 cases from 14 independent studies, there was a positive association between red meat consumption and NHL (summary RR 1.22, 95% CI, 1.03–1.44). Although results were not reported stratified by study design, this meta-analysis included the same 4 cohort studies as the first meta-analysis by Yang et al.,2 which showed a non-significant association among cohort studies. There was no significant association between processed meat consumption and NHL risk.
Within the European Prospective Investigation into Cancer and Nutrition (EPIC) study, which is included in the meta-analyses mentioned above, a high intake of poultry was related to an increased risk of NHL (RR per 10 g intake/day 1.56, 95% CI, 1.26–1.94).4 It has been hypothesized that an oncogenic poultry virus may be implicated in the pathogenesis, but this has not been proven. However, these results have not been replicated in other cohort studies and, therefore, should be interpreted with caution.
A meta-analysis of dairy consumption and the risk of NHL (16 studies, 4207 cases) divided dairy into 6 subgroups: total dairy, milk, cheese, butter, yoghurt, and ice-cream.5 It reported a linear relationship between total dairy consumption and NHL risk, but only in case-control and not cohort studies. Compared with 40 g of dairy consumption per day, 1500 g per day increased the risk of NHL by 42% (RR 1.42, 95% CI, 1.06–1.89). For every 200-g increase per day in total dairy consumption, the risk of NHL increased by 5% (RR 1.05, 95% CI, 1.00–1.10).
For milk only, a linear relationship was identified, showing that a 200-g increase of milk consumption per day resulted in a 6% increased risk of NHL (RR 1.06, 95% CI 0.99–1.13). The risk of NHL was also positively associated with cheese consumption (RR 1.14, 95% CI, 0.96–1.34). The pooled RR of NHL for butter and ice-cream consumption were 1.31 (95% CI, 1.04–1.65) and 1.57 (95% CI, 1.11–2.20), respectively, when comparing the lowest and highest consumption values.
Interestingly, the RR of NHL for yoghurt consumption was 0.78 (95% CI, 0.54–1.12). The authors suggest the presence of lactic acid bacteria may be an explanation for the cancer-protective effects of yoghurt consumption.
The interpretation of these data is limited by differences in results based on cohort versus case-control study design, inclusion of patients from different continents, and inconsistent use of validated food frequency questionnaires.
The French NutriNet-Santé prospective cohort study of 68 946 French adults reported a strong reduction in risk of NHL with consumption of organic food (HR = 0.14, 95% CI, 0.03–0.66).6 Only 1 other cohort study has, to date, assessed the association between organic food consumption and cancer risk.7 This was a prospective study of 623 080 middle-aged women in the United Kingdom. After 9.3 years of follow up, consumption of organic food was associated with an inverse risk of NHL (RR 0.79; 95% CI, 0.65–0.96). These associations are highly plausible given that the International Agency for Research on Cancer (IARC) has classified certain pesticides (glyphosate, malathion, diazinon) as carcinogenic in humans (group 2A) and all 3 pesticides were found to increase risk of NHL. However, further studies are needed for confirmation.
Fruits and vegetables
A systematic review and meta-analysis of 10 prospective cohort studies investigated the association between fruit and vegetable consumption and the risk of all haematological malignanices.8 Overall, total fruit and vegetable consumption, citrus fruit consumption, and cruciferous vegetable consumption were inversely associated with the risk of NHL. The summary RR was 1.03 (95% CI, 0.92–1.16, n = 7) for total fruit, 0.85 (95% CI, 0.73–1.00, P = 0.044, n = 4) for citrus fruit, 0.89 (95% CI, 0.79–1.00, n = 7) for vegetables, 0.84 (95% CI, 0.71–1.00, P = 0.047, n = 3) for cruciferous vegetables, 0.94 (95% CI, 0.64–1.37, n = 3) for green leafy vegetables, and 0.79 (95% CI, 0.65–0.96, n = 3) for fruit and vegetables combined.
In the available literature, there is evidence to suggest that certain foods or food groups and dietary patterns may influence the risk of developing NHL. Red meat consumption has been positively associated with the risk of developing NHL in two meta-analyses and processed meat and dairy consumption was associated with increased risk of NHL in one meta-analysis. However, the associations were only significant among case-control studies. Intake of total fruit and vegetables, cruciferous vegetables, and citrus fruits has shown an inverse association with NHL. Two cohort studies have reported inverse associations between organic food consumption and risk of NHL, and these findings are consistent with the recent assessment by the IARC of the carcinogenicity of certain pesticides.
Given that most of the current literature on diet and risk of NHL is based on case-control studies, which to a greater degree can be affected by recall and selection biases than cohort studies, additional well-conducted cohort studies with validated questionnaires, repeated measurements of diet, and appropriate adjustment for confounding factors are needed before firm conclusions can be made. To strengthen the evidence and provide more certainty, the underlying pathophysiological mechanisms should also be studied in more detail.
While the current evidence regarding diet and NHL may not be strong enough by itself for dietary recommendations to be made specifically for prevention of NHL, the findings are concordant with data regarding diet and risk of other cancers and chronic diseases and suggest that the current World Cancer Research Fund recommendations to limit the amount of red and processed meat and to increase the amount of fruit and vegetables eaten in a day also may reduce the risk of NHL. There is also suggestive evidence that eating cruciferous vegetables, citrus fruits, and organic foods may be particularly important for reducing the risk of NHL.
1. Global Burden of Disease Cancer Collaboration. Global, regional, and national cancer incidence, mortality, years of life lost, years lived with disability, and disability-adjusted life-years for 29 cancer groups, 1990 to 2016: a systematic analysis for the Global Burden of Disease Study. AMA Oncol. 2018;4(11):1553–1568. doi:10.1001/jamaoncol.2018.2706
2.Yang L, Dong J, Jiang S, et al. Red and processed meat consumption increases risk for non-Hodgkin lymphoma: a PRISMA-compliant meta-analysis of observational studies. Medicine (Baltimore). 2015;94(45):e1729. doi:10.1097/MD.0000000000001729
3. Caini S, Masala G, Gnagnarella P, et al. Food of animal origin and risk of non-Hodgkin lymphoma and multiple myeloma: a review of the literature and meta-analysis. Crit Rev Oncol Hematol, 2016;100:16–24. doi:10.1016/j.critrevonc.2016.02.011
4. Rohrmann S, Linseisen J, Jakobsen MU, et al. Consumption of meat and dairy and lymphoma risk in the European Prospective Investigation into Cancer and Nutrition. Int J Cancer. 2011;128(3):623–34. doi:10.1002/ijc.25387
5. Wang J, Li X, Zhang D. Dairy product consumption and risk of non-Hodgkin lymphoma: a meta-analysis. Nutrients. 2016;8(3):120. doi:10.3390/nu8030120
6. Baudry J, Assmann KE, Touvier M, et al. Association of frequency of organic food consumption with cancer risk findings from the NutriNet-Santé Prospective Cohort Study [published online October 22, 2018]. JAMA Intern Med.doi:10.1001/jamainternmed.2018.4357
7. Bradbury KE, Balkwill A, Spencer EA, et al. Organic food consumption and the incidence of cancer in a large prospective study of women in the United Kingdom [published online March 27, 2014]. Br J Cancer. 2014;110(9):2321–2326. doi:10.1038/bjc.2014.148
8. Sergentanis T, Psaltopoulou T, Ntanasis-Stathopoulos I, et al. Consumption of fruits, vegetables, and risk of hematological malignancies: a systematic review and meta-analysis of prospective studies. Leuk Lymphoma.2017;59(2):434–447. doi:10.1080/10428194.2017.1339873
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