Infectious diseases and risk of leukemia and non-Hodgkin's lymphoma: A case-control study
Introduction
Etiology of leukemia and non-Hodgkin's lymphoma (NHL) is largely unknown. The main recognized or alleged risk factors for both diseases include: smoking habit, exposure to radiation, chemotherapeutic agents, electromagnetic fields, pesticides, benzene and other hydrocarbons [1], [2]. Furthermore, impairment of the immune system was consistently associated with an increased risk of developing NHL [2].
A causal role of some viral agents was demonstrated in relation with adult T-cell leukemia (HTLV-1) and with some specific subtypes of NHL (HIV, EBV, and HHV-8), while the bacterium Helicobacter pylori was found to be associated with gastric lymphoma. However, it was estimated that all these infections could account for less than 10% of the total incidence of both malignancies [3].
Many investigations have pointed out an association between common communicable diseases and the risk of childhood leukemia, largely based on the observation of clusters of cases following mixing population and of a protective effect of multiple infections in childhood [3], [4], [5]. Even if the underlying biological mechanism remains to be clarified [6], [7], a possible role of such infections in the onset of adult leukemia and NHL was also proposed [3]. Evidence from many epidemiological investigations strongly supports this hypothesis for lymphomas occurring in adulthood, while for adult leukemia it remains less substantiated [3]. In particular, the association, repeatedly observed, between immunesuppression and the risk of developing NHL or Hodgkin's disease is consistent with the possibility of enhanced proliferation of potentially oncogenic viruses [2]. However, this association did not emerge for adult leukemia [3]. Furthermore, many studies on subjects professionally exposed to infectious agents by repeated contacts with humans (barbers, hairdressers, teachers and care attendants) or animals (farmers and butchers) reported an excess risk of NHL [2]. Finally, some investigations pointed out a protective role of some infectious diseases occurring during childhood on the risk of developing lymphomas during adulthood [8], [9], [10], [11], [12].
This case-control study is aimed at evaluating the association between infectious diseases and risk of leukemia and NHL in an adult population. Furthermore, the possible role of the place of residence during childhood, which could be associated with the incidence of some infectious diseases, was also investigated.
Section snippets
Study subjects
A population based case-control study was carried out in Savona Province (Northern Italy), with the main purpose of estimating the risk of leukemia and NHL in a population environmentally and occupationally exposed to potentially carcinogenic compounds. Results from the analysis of the main end-points will be published elsewhere, while the present paper is focused on the association between the risk of both malignancies and previous exposure to infectious agents.
Both cases and controls were
Results
Among the 939 originally identified subjects, 91 were excluded because they did not fulfill eligibility criteria, leaving 841 subjects eligible for the study. The proportion of subjects successfully interviewed was quite similar among the three ICD9 defined groups (69% leukemia cases, 74% NHL and 63% controls, respectively). Among them, 398 subjects (69% of the eligible individuals) were directly interviewed and further included in the analyses. At the light of the WHO classification they
Discussion
Results from many case-control investigations partly support the hypothesis of a protective effect of childhood infections on the risk of developing lymphoid malignancies in adults, even if evidence are in general limited to lymphomas. For instance, two large population based studies carried out in Canada and in Germany, showed a protective effect for measles and mumps [8] and for measles and pertussis [9], respectively. Interestingly, in the latter investigation, the risk was lower among those
Conflict of interest statement
All authors have no conflict of interest to report.
Acknowledgements
We are deeply indebted with Maria Antonietta Gioioso, Giovanni Olivieri, Giuliano Chiappa, Virna Frumento, Claudio Boffa and Margherita Costa (Savona Local Health Centre 2, ASL2 Savonese) who carried out the interviews, Maria Paola Briata (Savona Local Health Centre 2, ASL2 Savonese) who coordinated the interviewers activity, and Matteo Puntoni (Galliera Hospital of Genoa), and Fabio Montanaro (Data Management and Statistics Unit, Opera CRO, Via Sampierdarena 33/2, 16149 Genoa (Italy)) for data
References (26)
- et al.
Infective cause of childhood leukaemia and wartime population mixing in Orkney and Shetland, UK
Lancet
(2001) - et al.
Population-based study of lymphoma in Germany: rationale, study design and first results
Leuk Res
(2004) - et al.
Do childhood diseases affect NHL and HL risk? A case-control study from northern and southern Italy
Leuk Res
(2006) - et al.
Non-Hodgkin's lymphoma: case control epidemiological study in Yorkshire
Leuk Res
(1988) - et al.
Risk factors and primary prevention of acute leukemia
Asian Pac J Cancer Prev
(2006) - et al.
The non-Hodgkin lymphomas: a review of the epidemiologic literature
Int J Cancer
(2007) Childhood leukemias and other hematopoietic malignancies: interdependence between an infectious event and chromosomal modifications
Int J Cancer
(2009)- et al.
Leukemia and non-Hodgkin's lymphoma in children and young adults: are prenatal and neonatal factors important determinants of disease?
Br J Cancer
(1997) Infection immune responses and the aetiology of childhood leukaemia
Nat Rev Cancer
(2006)Epidemiological evidence for an infective basis in childhood leukaemia
Br J Cancer
(1995)
Non-Hodgkin's lymphoma and specific pesticide exposures in men: cross-Canada study of pesticides health
Cancer Epidemiol Biomarkers Prev
Medical history and risk of lymphoma: results of a European case-control study (EPILYMPH)
J Cancer Res Clin Oncol
Self-reported history of infections and the risk of non-Hodgkin lymphoma: an InterLymph pooled analysis
Int J Cancer
Cited by (8)
Herpes zoster as a marker of occult cancer: A systematic review and meta-analysis
2017, Journal of InfectionCitation Excerpt :A case-control design was used in 27 studies, which generally had the highest risk of bias. For example, 18 studies assessed history of herpes zoster through self- or proxy-report,47,50–52,54–56,58–61,68,69,71,75–77 without medical record verification in most studies. Eight case-control studies used hospital controls,50,51,54–56,59,68,71,77 which may have resulted in a non-representative sample of the frequency of herpes zoster in the source population.
Scarlet fever outbreak in a public school in Granada in 2012
2014, Anales de PediatriaThe end of measles and congenital rubella: An achievable dream?
2017, Annali di Igiene Medicina Preventiva e di ComunitaInvestigating the Relationship between Mortality from Respiratory Diseases and Childhood Acute Lymphoblastic Leukaemia in Hungary
2015, Pathology and Oncology Research