Chronic Fatigue Syndrome and Cancer

J of Chronic Fatigue Syndrome, Vol. 7(1) 2000 pp. 29-38

Paul H. Levine, MD; Deborah Pilkington, RN; Paula Strickland, PhD; Daniel
Peterson, MD

Affiliations:
Paul H. Levine and Paula Strickland are affiliated with the George
Washington University School of Public Health and Health Services,
Washington, DC.
Deborah Pilkington and Daniel Peterson are affiliated with Sierra
Internal Medicine Associates, Incline Village, NV.

Address correspondence to: Paul H. Levine, MD, George Washington
University School of Public Health and Health Services, Washington, DC
20037 (E-mail: mailto:sphphl@gwumc.edu).

ABSTRACT.
Several studies have indicated a link between chronic fatigue syndrome
(CFS) and cancer, most of them based on anecdotal observations. We have
attempted to use more population-based data to determine if the reported
relationship is meaningful. Two outbreaks of a fatiguing illness which
included well documented cases of CFS were evaluated ten years after the
reported outbreak for long-term effects, particularly cancer. We found an
unusual pattern of cancer which, in view of an increased incidence of
brain tumors and non-Hodgkin’s lymphoma (NHL) reported in other studies
involving CFS, indicates the need for further study. At the present time
this link, which is often presumed to be due to immune dysfunction, has
not yet been documented. Not all CFS patients have apparent dysregulation
of the immune system and a single causative agent is highly unlikely,
making the study of two heterogeneous illnesses, CFS and cancer, highly
problematic. With the continuing focus on subgroups, however, this area
of research may prove to be more productive.


KEYWORDS. Cancer, chronic fatigue syndrome, Epstein-Barr virus, human
herpesvirus-6, natural killer cells

INTRODUCTION

Chronic fatigue syndrome (CFS) is currently defined by a case definition
derived from clinical experience rather than systematically collected
data (1). It is apparent to both clinicians and laboratory investigators
that the recognition of CFS as a syndrome does not imply a single
etiology or a single pathogenesis. We have recently utilized a cohort of
30,000 veterans to show that factor analysis can be an important tool in
distinguishing different entities of possible etiologic importance in
Gulf War Syndrome (2), another disorder that shares with CFS the absence
of objective signs or laboratory tests, and subsequently identified by
factor analysis three distinct subgroups of CFS in this same cohort (3).
Therefore we agree with those investigators who believe that CFS is a
heterogeneous disorder which contains many different subtypes with
different clinical patterns and different laboratory features.

One of the subtypes that has been well recognized is CFS associated with
immune dysfunction (4-9). The laboratory test most consistently
identified as being abnormal in CFS patients, the natural killer (NK)
cell assay (4-7), involves a part of the immune system apparently related
to control of cancer cells (10). Early epidemiologic studies also
suggested a link between CFS and cancer (6,7), leading to our interest in
studying well described outbreaks of fatigue (11,12) which resulted in
patients developing CFS (13,14).

In order to evaluate this potential association on a systematic basis, we
followed up the outbreak of the fatiguing illness in northern Neva
da/California (11,13) and, using data from a population based Nevada
Cancer Registry, noted an increased rates of brain tumors and NHL in
northern Nevada, where the outbreak was reported, as compared to a
control population of similar composition in southern Nevada, where no
similar illness was reported (15). Since our report with the Nevada
Cancer Registry was not able to focus on patients with CFS, we
subsequently turned to a ten-year follow-up of the outbreak (16) to
determine if we could see an association between CFS and cancer in this
particular cohort.

While previous reports have suggested that CFS may predispose to cancer
(6,7), these reports are anecdotal. CFS is now more often considered an
immunologic or endocrinologic disorder (17) rather than an infectious
disease, although it frequently is reported as a consequence of
infection. The best documented precipitating agent is Epstein-Barr virus
(EBV) (18-20), which is suspected of causing a number of human tumors
(21), but CFS also has been noted to occur after infection with a variety
of other organisms, including cytomegalovirus, human herpesvirus-6
(HHV-6), and giardiasis (22). Apparent outbreaks of infectious disease,
often described as epidemic neuromyasthenia (23-25), have resulted in a
significant number of cases meeting the criteria for CFS (13,14). In this
report we describe an unusual pattern of cancer in the cohort identified
in northern California/Nevada.

Reported in part at the Second World Congress on Chronic Fatigue
Syndrome, Brussels, Belgium, September 9-11, 1999.


© 2000 by The Haworth Press, Inc. All rights reserved.