Altered Immunity as a Risk Factor for Non-Hodgkin Lymphoma

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Published online first on March 2, 2007

[Cancer Epidemiology Biomarkers & Prevention, 10.1158/1055-9965.EPI-06-1070]

Altered Immunity as a Risk Factor for Non-Hodgkin Lymphoma

E. Grulich 1*, M. Vajdic , Cozen

1 1National Centre in HIV Epidemiology and Clinical Research, University of New

South Wales, Sydney, Australia and 2Departments of Preventive Medicine and

Pathology, Keck School of Medicine, University of Southern California, Los

Angeles, California

* To whom correspondence should be addressed. E-mail:

agrulich@... .

Abstract

This review examines the association between disorders of immunity, including

immune deficiency, atopy, and autoimmune disease, and non-Hodgkin lymphoma

(NHL). Immune deficiency is one of the strongest known risk factors for NHL.

Risk is increased whether the immune deficiency is congenital, iatrogenic, or

acquired. Risk of NHL increases with degree of immune deficiency, and there is

no evidence of a threshold. In the profoundly immune deficient, NHL is

frequently caused by infection with the ubiquitous EBV. Whether mild,

subclinical immune deficiency is related to increased NHL risk is unknown. There

is inconsistent evidence that atopic conditions, such as asthma, hayfever, and

eczema, characterized by an immune response that is skewed toward Th2, are

associated with a decreased risk of NHL. These data come mainly from

case-control studies. Concern has been expressed that the association may be due

to reverse causality if early symptoms of NHL include a lessening of atopic

manifestations. Case-control and cohort studies of people with autoimmune

conditions have generally shown that rheumatoid arthritis, systemic lupus

erythematosis, and Sjogren's disease are associated with increased NHL risk. It

seems to be the intensity of the inflammatory disease rather than its treatment

which is related to increased risk of NHL. The study of altered immunity as a

cause of NHL in case-control studies is limited by the fact that development of

NHL in itself leads to altered immunity. Cohort studies of the role of altered

immunity should be a top priority in epidemiologic studies of NHL etiology.

(Cancer Epidemiol Biomarkers Prev 2007;16(3):405-8)