Chronic fatigue syndrome and subsequent risk of cancer among elderly US adults, 2012, Engels et al.

Chronic fatigue syndrome and subsequent risk of cancer among elderly US adults
Cindy M. Chang PhD, MPH, Joan L. Warren PhD, Eric A. Engels MD, MPH

Abstract
BACKGROUND:
The cause of chronic fatigue syndrome (CFS) is unknown but is thought to be associated with immune abnormalities or infection. Because cancer can arise from similar conditions, associations between CFS and cancer were examined in a population-based case-control study among the US elderly.

METHODS:
Using linked Surveillance, Epidemiology, and End Results (SEER)-Medicare registry data, approximately 1.2 million cancer cases and 100,000 controls (age range, 66-99 years; 1992-2005) were evaluated. CFS was identified in the period more than 1 year prior to selection, using linked Medicare claims. Unconditional logistic regression was used to estimate the odds ratios (ORs) comparing the CFS prevalence in cases and controls, adjusting for age, sex, and selection year. All statistical tests were 2-sided.

RESULTS:
CFS was present in 0.5% of cancer cases overall and 0.5% of controls. CFS was associated with an increased risk of non-Hodgkin lymphoma (NHL) (OR = 1.29, 95% confidence interval [CI] = 1.16-1.43, P = 1.7 × 10−6). Among NHL subtypes, CFS was associated with diffuse large B cell lymphoma (OR = 1.34, 95% CI = 1.12-1.61), marginal zone lymphoma (OR = 1.88, 95% CI = 1.38-2.57), and B cell NHL not otherwise specified (OR = 1.51, 95% CI = 1.03-2.23). CFS associations with NHL overall and NHL subtypes remained elevated after excluding patients with medical conditions related to CFS or NHL, such as autoimmune conditions. CFS was also associated, although not after multiple comparison adjustment, with cancers of the pancreas (OR = 1.25, 95% CI = 1.07-1.47), kidney (OR = 1.27, 95% CI = 1.07-1.49), breast (OR = 0.85, 95% CI = 0.74-0.98), and oral cavity and pharynx (OR = 0.70, 95% CI = 0.49-1.00).

CONCLUSIONS:
Chronic immune activation or an infection associated with CFS may play a role in explaining the increased risk of NHL.

https://acsjournals.onlinelibrary.wiley.com/doi/full/10.1002/cncr.27612
PDF: https://onlinelibrary.wiley.com/doi/pdfdirect/10.1002/cncr.27612

 

Interesting to see this paper.

The points that strike me:

1. The increased association with NHL is not that great at 1.29. It is potentially of scientific interest but tends to suggest an indirect or spurious link could be involved.
2. The CFS rate of 05% seems high.
3. The use of medical claims for diagnosis of CFS is clearly a worry in terms of reliability, certainly in terms of ME as defined as PEM-related.
4. The decision not to include CFS diagnosis in the year prior to cancer diagnosis does not seem adequate to exclude 'reverse causation' since people may feel unwell with NHL for years before it is diagnosed, although that would be more relevant to MZL than DLBCL I think.

I think the case for a causal link through immune activation is weak, although conceivable. If there was a causal link I would have expected a clear link to one particular form of lymphoma. For instance Sjögren's syndrome is specifically associated with MALT lymphoma, although MZL and DLBCL do also have higher rates.

My rough calculation is that about 1.5% of people end up with a NHL. This study suggests that maybe 1.9% of people with CFS would. It would be quite easy for that number of lymphoma cases to be mixed in with a broad group of 'CFS' without having much relevance to mechanisms specific to ME/CFS as we understand it (PEM+).

 

They acknowledge this but I am not convinced they have guarded against it well enough.