One approach for a better understanding of carcinogenesis is to modulate mutation rates with both genetic and environmental factors. Mice that were deficient in DNA mismatch repair (MMR) due to homozygosity for a null allele of Mlh1 develop normally but are prone to lymphomas, intestinal adenomas and carcinomas, and skin gland tumors [14
], on the other hand antioxidant-related nutrients can enhance DNA repair activity by modifying gene expression distinct from their direct antioxidant properties and are protective for lymphoma [15
]. In this study we aimed to show the effect of the most important environmental factor (diet) on NHL.
Diet is an important risk factor for many cancers. High fat/low calcium diets are associated with increased tumorigeneses, whereas caloric restriction reproducibly increases lifespan and decreases tumors. Excessive consumption of protein can result in immune unresponsiveness as a result of chronic hyperstimulation. In animal models, dietary fat suppresses the immune system [16
Patients who were HIV or HTLV1 positive, or received immunosuppressive therapy before they were diagnosed with lymphoma, were excluded from the study. Using the dietary intake during years before beginning of disease instead of the most recent diet helped to reduce bias.
The limitations of this study included: We could not measure the exact amounts of intakes. Some questions were not answered, and the moderate(no consume low or high) consumption of some food items led to smaller population analysis.
In this case and control study we found an increased risk of NHL with highest quartile intakes of protein rich products, particularly for fried and grilled meat, processed meat( hamburger, sausage), fats, and sweets, and a decreasing risk was found for fresh fruits, vegetables, and soft drinks.
One of the major findings from our study was an increased risk of NHL associated with a higher consumption of proteins and fats. There are different results from previous studies which focus on fat and protein intakes as risk factors for NHL. A large case and control study has suggested that high consumption of fats, meat, and dairy products may increase the lymphoma risk [17
]. Erber E et al [18
] in their study showed that fat and meat consumption was associated with a fivefold higher risk of follicular lymphoma in men (Ptrend
= 0.03). The other population-based case–control study suggests that meat consumption, well-done or not, does not increase the risk of NHL, meanwhile fat intake was associated with a significantly increased risk for NHL [10
]. A previous cohort study [19
] and a case–control study [20
], similar to our study, found an increased risk for NHL in the highest tertile of red meat consumption, the cohort study identified that the main component contributing to this risk was hamburgers. The large case and control study showed an increased risk of NHL with high intakes of processed meat, cheese, eggs, and dessert foods and a positive associations with NHL were also found for high consumption of total fat [21
Not only food components may be associated with cancer risk, but also cooking methods can significantly increase cancer risk [22
]. Our study found an association with red meat, processed meat and the risk of NHL. Processed meat (hamburger and susage), fried and grilled red meat were associated with the highest risk, but boiled chicken was associated with the least risk of NHL. Carcinogens and mutagens, such as heterocyclic amines can be generated during cooking red meat; it has been shown that these compounds can induce immunotoxicity and lymphoma [23
Tongzhang. Z et al [24
] reported a significantly increased risk of NHL associated with animal protein(OR, 1.7 95% CI 1.2,2.4) and saturated fat(OR,1.9 95%CI 1.1,2.3). In our study animal and saturated fat intakes were associated with an increased risk of lymphoma. An increased risk of NHL associated with a high fat diet may lead to altered immunocompetence, and immune system impairment by acting on the cyclogenase, lipoxygenas, or cytochrome P-450 pathways or directly on cell function through its effects on cell membrane structure and function. Alteration in dietary fat was found to alter membrane phospholipid fatty acid composition in a variety of cellular and subcellular membranes; such alteration in lymphocytes, could lead to impaired immune function [23
In this study all fresh fruits (including: a) citrus, b) apple, pear, peach, c) melon and water melon, e) grapes plums), green and other vegetables except root vegetable intakes were found to have a significantly inverse relationship with the risk of NHL, but compotes and juices were associated with an increased risk of NHL. Based on this result, we can say that the fiber of fruits and vegetables has an important role in protection against cancers.
Several studies support an inverse association between intakes of fruits and vegetables and the NHL risk. Particularly vegetables consumption may relate to the induction of apoptosis and the growth arrest in preneoplastic and neoplastic cells, two important actions of isothiocyanates that can be found in cruciferous vegetables [17
]. Sauvaget et al [25
] have examined a cohort of more than 36000 atomic-bomb survivors of Hiroshima and Nagasaki, an estimation of the radiation dose and the history of their diet were available. They evaluated the joint effect of radiation exposure and fruit and vegetable consumption on the risk of cancer death. They concluded that a regular intake of fruit or vegetables reduced this risk significantly in people exposed to radiation. Linda E Kelemen. Et al [15
] in their study mention that higher intake of vegetable, lutein zeaxanthin, and zinc are associated with a lower NHL risk. Several other studies including Han, X et al [26
], Talamini R. et al [27
], Cross, AJ et al [28
], Zheng, TZ et al [29
], Thompson, C. A. et al [30
] Chang, E. T.et al [31
] found that high consumption of fruits and vegetables was associated with the reduced risk of NHL. Chiu BC et al [32
] did not find an association between vegetables and lymphoma. Carrie A. et al [33
] found 32% better overall survival for NHL patients who had a higher pre-diagnosis intake of fruits and vegetables.
Vegetables and fruits rich in antioxidant nutrients are hypothesized to be chemoprotective against many type of cancer, including lymphoma, by several mechanisms including reduction of reactive oxygen species responsible for oxidative DNA damage, regulation of cell survival and apoptosis pathway, and protection of immune responses [34
]. In addition Franceschi et al [35
] hypothesized that alimentary fibers may affect the dilution, absorption, and/or breakdown of fat and animal protein in the gut, either directly or indirectly by modifying the gut microflora.
In this study we found that the consumption of carbohydrate rich products (OR, 1.865 Ptrend
=0.038) and sweets (OR, 8.806 Ptrend
=0.000), were associated with an increased risk of NHL. Among carbohydrate products, traditional bread and rice were associated with a decreased risk but white bread and macaroni were associated with an increased risk (). Zheng et al [27
] reported that white bread one of the major source of transunsaturated fat intake, was associated with an increased risk of NHL in their study.
Odd ratios and 95% CIs for non-Hodgkin's lymphoma by categories of dairy, carbohydrates and sweets
Sweets group, including all kinds of sweets and biscuits, jams and jellies were associated with an increasing risk of NHL. It hypothesized that insulin and insulin like growth factor effect human cell growth particularly on lymphoid, erythroid and myeloid cells. In addition, insulin like growth factor has a proliferative effect on lymphoma and leukemic cells [25
].The state of hyperglycemia is also known to initiate a reactive oxygen species chain reaction and to activate several proinflammatory cytokines, such as interleukin-6 and TNF-a, which have a role in NHL pathogenesis [36
The other finding in our study was the relation of dairy product with the risk of NHL. Overall, milk was associated with a decreased risk. We found that low fat milk, yoghurt, and buttermilk, were associated with a decreased risk, but fatty milk and cheese were associated with an increased risk of NHL. Ross and Bras [37
] have reported an increased risk of lymphoma in experimental rats after augmentation of the diet with casein, the major protein of milk. All positive findings would need to be confirmed in a different follow up study.