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Dietary patterns and chronic lymphocytic leukemia
system over the current sample. Scores of adherence to dietary patterns can be calculated following the exact same rules over different populations, resulting in differ- ent levels of adherence while still being valid, as has been recently proved.35 As a matter of fact, the current dietary patterns had previously been constructed in the MCC- study and a Western dietary pattern was positively associ- ated with gastric,48 breast49 and colorectal50 cancers.
One of the main limitations is the study design since case-control studies are prone to selection and recall bias- es. Measurement errors in the estimation of food intake due to the use of self-reported FFQ are also of some con- cern. However, the FFQ was validated in the Spanish pop- ulation and included regional products.32 Moreover, some questions about general dietary habits were included in the questionnaire and were used to adjust the responses to the FFQ following the methodology described in Calvert et al.33 The inclusion of prevalent cases might be another cause for concern since patients who survived might have a very different etiology than those who died soon after diagnosis. In addition, diet can be influenced by many external factors and patients who survive longer might have substantially modified their diet. However, results of the sensitivity analysis suggested that the use of prevalent cases might not have introduced selective survival bias or reverse causation. We may have been limited by the small sample size and lack of statistical power to detect signifi- cant associations when evaluating certain subgroups. Finally, although we adjusted for a range of potential con- founders, residual confounding factors cannot be totally ruled out.
The strengths of the study include the substantial sam- ple size of CLL cases, with specific information on clinical presentation. We were able to collect detailed information on demographics and disease stage, and statistically adjust for a number of potential confounding factors. This allowed the evaluation of potential interactions of diet
with numerous covariates and the exploration of the asso- ciations by stage. Finally, the multi-centric nature of the study, including both rural and urban areas, provided a wide geographic variability of dietary intake data.
In conclusion, in this Spanish population-based case- control study, greater adherence to a Western dietary pat- tern was associated with CLL. These novel results suggest that a proportion of CLL cases could be prevented by modifying dietary patterns. Further research, especially with a prospective design, is warranted to confirm these findings.
Acknowledgments
The authors would like to thank all the subjects who partici- pated in the study and all CLL MCC-Spain collaborators (the list can be found the Online Supplementary Appendix, List S1).
Funding
Predoctoral contract to MS (CIBERESP), Spanish Ministry of Economy and Competitiveness Juan de la Cierva de Incorporación grant IJCI-2014-20900. Spanish Ministry of Economy and Competitiveness - Carlos III Institute of Health cofunded by FEDER funds/European Regional Develpment Fund (ERDF) - a way to build Europe [(grants PI17/01280, PI11/01810, PI14/01219, PI11/02213, PI09/1662, PI15/00966, RCESP C03/09, RTICESP C03/10, RTIC RD06/0020/0095, RD12/0036/0056, Rio Hortega CM13/00232, SV-09-CLINIC-1 and Centro de Investigación Biomédica en Red: Epidemiología y Salud Pública (CIBERE- SP))] and the Agència de Gestió d'Ajuts Universitaris i de Recerca AGAUR (2017SGR1085, 2014SGR756). The ICGC CLL-Genome Project was funded by Spanish Ministerio de Economía y Competitividad (MINECO) through the Instituto de Salud Carlos III (ISCIII), PMP15/00007 and Centro de Investigación Biomédica en Red: Oncología (CIBERONC). ISGlobal is a member of the CERCA Programme, Generalitat de Catalunya.
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