To our knowledge, this is the first epidemiological study investigating risk factors associated with MBL in the general population. In contrast to CLL, the male predominance was not observed for “low-count” MBL in our data whereas, as expected, OR of cases increased with increasing age. Our main findings were that lifetime exposure to several infectious agents might be associated with MBL aetiology.
Assuming that MBL, in particular CLL-like subtype, is a precursor of CLL 
, our findings are consistent with previous studies on CLL reporting that a personal history of pneumonia was associated with subsequent development of CLL 
. Recent data also showed an increased risk of hospitalisation for infections among newly diagnosed clinical MBL than controls 
. Since general population “low-count” CLL-like MBL is 100 times more common than CLL among the elderly 
and persists over time without clinical progression 
, it was therefore postulated that “low-count” CLL-like MBL are less likely than clinical CLL-like MBL to progress to CLL: among 76 examined patients (median age: 66 years; range: 25–92 years) with low-count population-screening CLL-like MBL, none developed CLL after a 3-year median follow-up, even if they were found to carry 13q deletion with the same frequency to that observed in patients with newly diagnosed CLL and clinical MBL 
. Hence, “low-count” CLL-like MBL might even be a normal stage of the immunosenescence process 
. The observed link with infections for “low-count” CLL-like MBL might appear of limited value if the rate of progression of “low-count” CLL-like MBL to CLL is very low; however this progression rate is still unknown and large prospective studies are needed to evaluate which patients with MBL will advance to CLL. The progression from CLL-like MBL of “low-count” or clinical populations to CLL might then be due to the occurrence in MBL cells of specific biological and molecular profiles 
, potentially combined with exposure to some unknown environmental risk factors. Several hypotheses have been advanced to explain an infectious route in CLL. Accordingly, recent reports 
suggest that chronic and persistent antigenic stimulation may have a role in MBL and CLL aetiology and, respiratory tract infections could particularly be triggers for CLL development 
. Hepatitis C virus has also been suggested as a potential candidate for dysregulation of the immune system with recent data showing that the three MBL subtypes are more frequent in HCV infected individuals than in the general population 
. In our data, we could not distinguish between the different hepatitis and no statistical significant association was observed with overall self-reported history of hepatitis or vaccination against hepatitis.
We observed that family history of cancer in particular haematological cancers was more common in patients with MBL than controls. In the published literature, MBL is indeed more frequent in families with CLL cases, in particular among first-degree relatives of patients with familial CLL 
. Unfortunately, we could not differentiate here the association by haematological subtypes as this information was unavailable. In relation to the use of diabetes treatment and chronic lymphocytic leukaemia, data in the literature is inconsistent; while some authors report an increased risk of CLL among diabetic patients 
, others suggest a lower risk of lymphoma 
and other cancers 
particularly when using metformin. Further studies are needed to clarify this finding.There are several limitations of this study. The questionnaire provided limited information on occupation (either job title or company type/name was reported). Hence, occupational exposure to contaminants, organic solvents, herbicides or infections could not be examined. Furthermore the origin and type (viral/bacterial and chronic/acute) of infections that occurred among the children and other family members were not specified. However, this type of data is clearly difficult to collect in epidemiological settings. Other potential limitations of our study are the lack of validation of self-reports of family history even though questionnaires were filled in with general practitioners, as well as the limited information on timing of infection relative to date of recruitment. Despite the fact that the number of cases in each stratum was relatively small for some categories and that the number of comparisons performed was high, our results point out a potential role of infectious agents in the development of “low-count” MBL in the general population, particularly of those involved in respiratory infections. However, a reverse causality effect that would result on detecting a more suppressed immune system among subjects with MBL or already in the pathway of CLL cannot be excluded, as decreased numbers of normal PB B-cells as well as CD4+CD8+ double-positive T-cells have been specifically reported in "low-count” MBL 
. Recent findings showing that regulatory T-cells increase gradually from controls to “clinical” MBL to CLL 
, and that most “low-count” MBL subjects show T-cell clones especially among CD4+CD8+ T-cells 
further support the hypothesis of an altered immune system of MBL patients. Further studies analyzing dysregulations of the immune system in MBL compared to controls are required. Although selection biases cannot be ruled out, the robustness of the study relies in that neither the interviewers nor the study subjects were aware of the MBL status. This small exploratory study provides initial insights and directions for future research. Further studies are needed to evaluate the association between MBL and CLL and to examine the role of infectious agents in the development and progression of both entities.