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M. Solans et al.
Introduction
Chronic lymphocytic leukemia (CLL) is the commonest leukemia among the adult population in Western coun- tries, with an annual incidence rate of around 5 per 100,000 person-years in Europe,1 but its etiology is still poorly understood. A pooled analysis of 2440 CLL cases and 15,186 controls from the InterLymph consortium showed significant inverse associations with atopic condi- tions, smoking, blood transfusion history, and recreational sun exposure, and positive associations with height, hep- atitis C virus seropositivity, living or working on a farm, working as a hairdresser, and family history of hematolog- ic malignancies.2
Diet is a modifiable risk factor for several neoplasms,3 but evidence for CLL is inconclusive. Epidemiological data on the association of diet and CLL are heterogeneous, and mainly arise from studies on nutrients or single food items. While most prospective studies4-12 did not find any association with a wide range of dietary factors, case-con- trol studies13-25 have yielded contradictory results for items such as meat, dairy or vegetable intake. Some authors argue that focusing on overall dietary patterns instead of on individual foods or nutrients may better capture dietary variability in the population’s diet while allowing the evaluation of interactions between dietary factors.26 However, the few studies that have been conducted on overall diet and CLL25,27,28 reported inconclusive findings, mainly due to small sample size.
A population-based multicase-control study (MCC- Spain) was launched to evaluate the influence of environ- mental exposures and their interaction with genetic fac- tors in CLL, among other cancers.29 The aim of the present study was to evaluate the association between adherence to three validated dietary patterns,30 Western, Prudent and Mediterranean, and CLL in the MCC-Spain study.
Methods
Study population
MCC-Spain is a multicentric case-control study with population controls and cases with common tumors (prostate, breast, colorec- tal, gastroesophageal and CLL) in Spain. Between 2010 and 2013, CLL cases aged 20-85 years were recruited in 11 Spanish hospitals from 5 Spanish provinces (Asturias, Barcelona, Cantabria, Girona and Granada). Simultaneously, population-based controls frequen- cy-matched to cases according to age (5-year intervals), sex, and province of recruitment were randomly selected from primary care centers within the hospitals’ catchment areas. Participation rates were 87% in cases and 53% in controls, with variability among geographical regions. After applying specific diet exclusion criteria (excluding participants with no dietary data or with miss- ing or implausible energy intakes under 750 or over 4500 kcal/day), a total of 1605 controls and 369 CLL cases were includ- ed in the study. All participants gave informed consent. Approval for the study was obtained from the ethical review boards of all recruiting centers. Additional information regarding the study design has been provided elsewhere.29
Outcome definition
Chronic lymphocytic leukemia cases were diagnosed according to the International Workshop on CLL criteria: presence of an absolute count ≥5 x109 B cells/L for three or more months in peripheral blood and a clonal population of CD5+, CD19+, and
CD23+ B cells.31 All diagnoses were morphologically and immuno- logically confirmed using flow cytometry immunophenotype and complete blood cell count. CLL and small lymphocytic lymphoma were considered the same underlying disease. Given the indolent course of the disease, CLL cases were recruited and interviewed within three years from diagnosis. Disease severity at interview was evaluated using the Rai staging system obtained from medical records and verified by local hematologists. CLL subjects were then categorized into two groups based on Rai stage: a) low-risk category including asymptomatic patients with lymphocytosis only (Rai 0); and b) intermediate/high-risk category including patients with either lymphadenopathy, hepatomegaly, splenomegaly, anemia and/or thrombocytopenia (Rai I-IV).
Data collection
Data on socio-demographic factors, lifestyle and personal/fam- ily medical history were collected through face-to-face interviews performed by trained personnel. Height and weight at different ages were self-reported. The questionnaire in Spanish is available at www.mccspain.org.
In addition, subjects were provided a semi-quantitative Food Frequency Questionnaire (FFQ), which was a modified version from a previous tool validated in Spain to include regional prod- ucts.32 The FFQ was self-administered and returned by mail or filled out face-to-face. It included 140 food items with portion sizes specified for each item, and assessed usual dietary intake during the previous year. Cross-check questions on aggregated food group consumption were used to adjust the frequency of food consumption and reduce misreporting of food groups with large numbers of items.33 Nutrient intakes were estimated using food composition tables published for Spain, and other sources.34 The response rate of the FFQ was slightly lower in cases (82%) than in controls (87%). Overall, responsiveness was not associated with age, and individuals from Granada were less likely to answer the FFQ than those from Barcelona. Those individuals who did not answer the diet questionnaire had a lower level of education and, in controls, were also more likely to be women.
Dietary patterns
Three validated dietary patterns identified in a Spanish case- control study (EpiGEICAM)30 were reconstructed in the MCC- study: a) a Western dietary pattern characterized by high intake of high-fat dairy products, processed meat, refined grains, sweets, caloric drinks, convenience food and sauces; b) a Prudent pattern, with high intake of low-fat dairy products, vegetables, fruits, whole grains and juices; and c) a Mediterranean pattern, defined by a high intake of fish, vegetables, legumes, boiled potatoes, fruits, olives, and vegetable oil. Further information on identifica- tion of the dietary patterns can be found elsewhere.30 In brief, dietary information extracted from a semi-quantitative question- naire in the EpiGEICAM study was converted to mean daily intake in grams and grouped into 26 food categories. Major exist- ing dietary patterns were identified in the control population by applying principal components analysis (PCA) without rotation of the variance-covariance matrix over the 26 inter-correlated food groups. The set of loadings obtained represent the correlation between the consumption of each food group and the compo- nent/pattern score, and can be used to apply such patterns to other populations.35 In the MCC-study, we grouped the FFQ items into thesame26foodgroups(OnlineSupplementary TableS1),andcal- culated the score of adherence to the Western, Prudent and Mediterranean dietary patterns as a linear combination of the loads described in the EpiGEICAM study and the log-transformed centered food group consumption reported by the participants of MCC-Spain study.
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haematologica | 2018; 103(11)