This prospective cohort study is, to our knowledge, the first epidemiological study to investigate the association between dietary acrylamide intake and the risk of specific histological subtypes of lymphatic malignancies. Because of this, the results of this study are challenging, but should be interpreted cautiously. We observed a positive association for multiple myeloma in all men and never-smoking men, and for follicular lymphoma in all men.
In the Finnish ATBC Study, no association was observed between dietary acrylamide intake and the risk of lymphomas in male smokers 
. In that study, no analyses were done for histological subtypes of lymphatic malignancies, and therefore an association with a specific type of lymphatic malignancy might have been obscured. In addition, when studying the link between dietary acrylamide intake and cancer risk, it is better to study non-smokers as a subgroup, because cigarette smoke is a much more important source of acrylamide than diet is and it might therefore blur the association between acrylamide through diet and cancer risk.
Possible risk factors for lymphatic malignancies, such as height, overweight, hormones and nutrients, have shown contradictory results in epidemiological studies 
. Although there is thus no strong epidemiological evidence for risk factors for lymphatic malignancies, in the present study we checked the confounding potential of a broad range of possible risk factors for lymphatic malignancies and cancer in general. Human immunodeficiency virus (HIV) infection has been associated with an increased risk of lymphatic malignancies 
. Data on the prevalence of HIV in our study population was not available, but the prevalence was likely low, considering the age segment of our population. We were able to check for other immune system-related diseases, such as asthma and tuberculosis, but these diseases were not found to be confounders for the association between acrylamide intake and the risk of lymphatic malignancies.
The present study has some limitations that should be discussed. The associations between dietary acrylamide intake and multiple myeloma in never-smoking men, and the association for follicular lymphoma in all men were based on analyses with a small number of cases. This makes it likely that some of the observed associations are spurious. Therefore, these results should be interpreted cautiously. Moreover, we analyzed associations in many subtypes of lymphatic malignancies and for several subgroups within each subtype, which makes it likely that chance findings have occurred. The same applies to the subgroup analyses that were done to investigate interaction with CYP2E1-influencing variables. However, the indications for possible interaction with smoking and alcohol are intriguing, although based on analyses with a small number of cases, as both smoking and alcohol intake were inversely associated with the glycidamide to acrylamide hemoglobin adduct ratio in a cross-sectional population study 
In addition, this study has some limitations regarding acrylamide intake assessment. Firstly, within foods, acrylamide levels vary greatly, which leads to non-differential misclassification of acrylamide intake when assigning a single mean acrylamide value to a food, which most likely biases risk estimates towards null. This means that true risks, if any, are probably greater than the risks presented here. Moreover, a recent study has shown that it is feasible to make a sound rank ordering of the acrylamide intake via a 24-hour meal using the mean acrylamide levels used in the NLCS study for individual foods. 
. Secondly, the acrylamide values in our food database were derived from foods that were sampled in 2002 and 2005. They may not be completely representative of the foods that were on the market in 1986. Thirdly, the FFQ did not provide information on which foods were prepared at home and how this was done. Both aspects too will have resulted in some non-differential misclassification of the intake, which will then most likely have led to underestimation of the true risks. Despite the fact that the use of an FFQ has limitations for the assessment of dietary acrylamide exposure, as is extensively discussed elsewhere 
, it is the only feasible way to assess dietary acrylamide intake over a long period of time in a large study population.
Although we have no direct data for acrylamide itself, the reproducibility and validity of the NLCS FFQ for acrylamide can to some extent be derived from nutrients that are correlated to acrylamide, namely carbohydrates and dietary fiber. The decline of the correlation between the baseline questionnaire and the questionnaire administered after 5 years of follow-up was 0.07 on average among the nutrients that were tested. This indicates that, although the questionnaire was administered only once, it characterizes long-term food intake for over a period of at least five years 
. As for validity, the correlation coefficients between the FFQ and a dietary record method were 0.77 for carbohydrates and 0.74 for fiber. For the food groups potatoes, bread, and cakes and cookies, Spearman correlation coefficients were 0.74, 0.80 and 0.65, respectively 
The large study size and the prospective nature of this NLCS are important strengths of this study. Selection bias is unlikely to occur, as the follow-up of the participants was complete. Due to the prospective design of the study, recall bias is absent. In addition, we were able to obtain a dietary acrylamide intake estimate representative for the Dutch study population, by estimating acrylamide levels in several batches of various Dutch food products that were specific for the population under study. The large study size enabled us to study specific histological subtypes of lymphatic malignancies that differ in their etiology and, as indicated by this study, may differ regarding their association with dietary acrylamide intake.
Recent analyses within the NLCS, the Nurses’ Health Study, and a Danish cohort study 
showed a positive association for endometrial, ovarian, and estrogen receptor-positive breast cancer, suggesting that disturbance of sex hormonal balances may be a mechanism of acrylamide carcinogenesis, which can also be suggested based on the rat carcinogenicity assays 
. Although it cannot be concluded from the present study, hormonal imbalances might be a mechanism of acrylamide carcinogenesis for lymphatic malignancies as well. Men have a higher incidence of lymphatic malignancies than women 
, but the reasons for this higher incidence are not known. Sex hormones have been shown to influence the immune system 
and may thus be at the basis of this observed difference. Estrogen receptor expression in lymphocytes suggests that estrogen bioavailability may be relevant to the pathogenesis of lymphomas 
. For multiple myeloma, studies investigated the mechanism of anti-estrogens (AEs), and showed that AEs inhibit cell cycle progression of malignant multiple myeloma cells and/or induce apoptosis in these cells 
. Other studies suggest that hormone-related and reproductive factors are involved in the etiology of lymphatic malignancies 
, and in a different way for men and women 
, but the results are inconsistent.
This is the first epidemiological study to investigate the association between dietary acrylamide intake and the risk of lymphatic malignancies. It provides indications that acrylamide may increase the risk of multiple myeloma and follicular lymphoma, but on the basis of the present study alone, we cannot conclude whether these results reflect true biological effects or are chance findings. We recommend that this possible modifiable risk factor for lymphatic malignancies is investigated in other prospective studies.