The characteristics of cases and controls are presented in . Most subjects were white, male, and selected between 1999 and 2005. Cases and controls were well matched by sex, age, and calendar year of diagnosis/selection, and differed slightly by race and duration of Medicare coverage. The most inclusive definition of CFS (CFS1), based on either ICD-9 300.5 or ICD-9-CM 780.71 in any calendar year, had a prevalence of 0.5% among controls (498 of 100,000 controls selected in 1992–2002). CFS defined by ICD-9-CM 780.71 in 1998 and later (CFS2) had a similar prevalence of 0.7% among controls (444 of 65,465 controls selected in 1999–2002).
Characteristics of cases and controls in the SEER-Medicare case-control study
Neither CFS1 nor CFS2 was associated with cancer overall (both ORs=0.99) (). Using the broadest definition of exposure, CFS1 was most strongly associated with elevated risk of NHL (OR=1.29, 95% CI=1.16–1.43, p-value=1.7 × 10−6), kidney cancer (OR=1.27, 95% CI=1.07–1.49, p-value=0.005), and pancreatic cancer (OR=1.25, 95% CI=1.07–1.47, p-value=0.006), and there was an inverse association with breast cancer (OR=0.85, 95% CI=0.74–0.98, p=0.025) and cancers of the oral cavity and pharynx (OR=0.70, 95% CI=0.49–1.00, p=0.049) (). CFS2 was similarly associated with elevated risk of NHL (OR=1.22, 95% CI=1.09–1.37, p=4.6 × 10−4), kidney cancer (OR=1.29, 95% CI=1.09–1.53, p-value=0.004), and pancreatic cancer (OR=1.27, 95% CI=1.07–1.50, p-value=0.006), and reduced risk of breast cancer (OR=0.85, 95% CI=0.74–0.99, p=0.034) and cancers of the oral cavity and pharynx (OR=0.65, 95% CI=0.44–0.97, p=0.033). Additionally, CFS2 was associated with reduced risk of gall bladder and bile duct (OR=0.71, 95% CI=0.51–0.97, p=0.032).
Associations between chronic fatigue syndrome and cancera
Among NHL subtypes (), CFS1 was significantly associated with diffuse large B cell lymphoma (DLBCL) (OR=1.34, 95% CI=1.12–1.61, p-value=0.002), marginal zone lymphoma (MZL) (OR=1.88, 95% CI=1.38–2.57, p-value=6.5 × 10−5), and B-cell NHL, not otherwise specified (NOS) (OR=1.51, 95% CI=1.03–2.23, p-value=0.037). The significant associations for CFS1 were also significant or borderline for CFS2. We repeated the analysis to exclude an additional year of Medicare claims for subjects, so that cases must have developed NHL at least 2 years after a CFS diagnosis, and results were similar. Specifically, associations remained apparent for CFS1 with NHL overall (OR=1.33, 95% CI=1.17–1.63, p-value=1.2 × 10−5), DLBCL (OR=1.44, 95% CI=1.16–1.79, p-value=0.001), and MZL (OR=2.16, 95% CI=1.47‒3.18, p-value=9.8 × 10−5), and for CFS2 with NHL overall (OR=1.21, 95% CI=1.05–1.39, p-value= 0.009), DLBCL (OR=1.18, 95% CI=0.92–1.53, p-value=0.190), and MZL (OR=1.83, 95% CI=1.21–2.77, p-value=0.004).
Associations between chronic fatigue syndrome and NHL subtypesa
In analyses adjusted for race, associations between CFS and NHL overall, DLBCL, and MZL remained the same (results not shown). Associations of CFS1 with various demographic characteristics and medical conditions are shown in for control subjects. CFS was more common among individuals who had a blood transfusion, or had HCV infection, Sjogren’s syndrome, or rheumatoid arthritis. Nonetheless, after excluding subjects with a history of transfusion, HIV, HBV, HCV, lupus, Sjogren’s syndrome, or rheumatoid arthritis, the associations with CFS1 were still significant for NHL overall (OR=1.33, 95% CI=1.19–1.49, p-value= 8.5 × 10−7) as well as for DLBCL (OR=1.35, 95% CI=1.10–1.65, p=0.003) and MZL (OR=2.04, 95% CI=1.46–2.85, p-value=3.3 × 10−5).
Associations of chronic fatigue syndrome† (N=498) with medical conditions among controls (N=100,000)
Because depression and CFS can be confused, we examined associations of NHL with depression. Depression was not associated with NHL overall (OR=0.99, 95% CI=0.96–1.03), DLBCL (OR=0.94, 95% CI=0.88–1.01), or MZL (OR=0.96, 95% CI=0.84–1.11).