Does tuberculosis (TB) increase the risk of cancer?

Ample reports in the literature suggest that TB is associated with the development of certain cancers, including lung cancer, lymphoma and urothelial cancers of the genitourinary tract. 1-5

A 2010 literature review including 9 retrospective studies found that several (not all) studies reported a significant association between prior history of TB and lung cancer, with odds ratios as high as 20.5 ( C.I. 8.1-51.8) at 1-5 years following TB.1 One study involving non-smoking women found a lung cancer (mostly adenocarcinoma) prevalence of 18% among those with prior history of TB (O.R. 5.9, CI 1.3-25.9).5 Cases of “pyothorax-associated lymphoma” of the pleural cavity have also been attributed to TB diagnosed as remote as 40 years or greater before the diagnosis of cancer.1

Urinary tuberculosis was associated with the development of urothelial carcinoma (including bladder, ureteral, renal pelvic transitional cell carcinoma) but not renal cell carcinoma in a nationwide cohort study from Taiwan (hazard ratio 3.4, C.I. 2.0-5.7). 2 The mean interval between the index date of TB and the diagnosis of urinary tract cancer was about 5 years in this study.

Several potential mechanisms for TB predisposing to malignancy have been proposed.1,6 Chronic inflammation associated with higher rate of cell turnover may increase the risk of genetic mutation and subsequent malignancy, as observed in other conditions such as gastroesophageal reflux disease and esophageal cancer and inflammatory bowel disease and colon cancer. The ability of Mycobacterium tuberculosis to induce DNA damage, inhibit apoptosis and augment concentrations of leukotrienes, prostaglandins and vascular endothelial growth factors have also been implicated.

And don’t forget that active TB may not only coexist with but may also mimic malignancy (see related pearl on P4P).

 

Bonus Pearl: Did you know that the association of TB with cancer was first described in 1810 by Gaspard Laurent Bayle, a French physician who considered “cavitation cancereuse” as a distinct TB category? 1

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 References

  1. Falagas ME, Kouranos VD, Athanassa Z, et al. Tuberculosis and malignancy. Q J Med 2010;103: 461-87. Doi:10.1093/qjmed/hcq068 https://pubmed.ncbi.nlm.nih.gov/20504861/
  2. Lien YC, Wang JY, Lee MC, et al. Urinary tuberculosis is associated with the development of urothelial carcinoma but not renal cell carcinoma: a nationwide cohort study in Taiwan. B J Cancer 2013;109:2933-2940. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3844900/
  3. Chin SN, Foster T, Char G, et al. Concomitant urothelial cancer and renal tuberculosis. Case Reports in Urology. Volume 2014, Aricle ID 625153. https://www.hindawi.com/journals/criu/2014/625153/
  4. Dobler CC, Cheung K, Nguyen J, et al. Risk of tuberculosis in patients with solid cancers and haematological malignancies: a systematic review and meta-analysis. Eur Respir J 2017;50:1700157. https://doi.org/10.1183/13993003.00157-2017.
  5. Ko YC, Lee CH, Chen MJ, et al. Risk factors for primary lung cancer amng non-smoking women in Taiwan. Int J Epidemiol 1997;26:24-31. https://pubmed.ncbi.nlm.nih.gov/9126500/
  6. Ling S, Chang X, Schultz L, et al. An EGFR-ERK-SOX9 signaling cascade links urothelial development and regeneration to cancer. Cancer Res 2011;71:3812-21. https://pubmed.ncbi.nlm.nih.gov/21512138/ 

Disclosures: The listed questions and answers are solely the responsibility of the author and do not necessarily represent the official views of Massachusetts General Hospital, Harvard Catalyst, Harvard University, its affiliate academic healthcare centers, or its contributors. Although every effort has been made to provide accurate information, the author is far from being perfect. The reader is urged to verify the content of the material with other sources as deemed appropriate and exercise clinical judgment in the interpretation and application of the information provided herein. No responsibility for an adverse outcome or guarantees for a favorable clinical result is assumed by the author. Thank you!

Does tuberculosis (TB) increase the risk of cancer?

My patient with COPD exacerbation on corticosteroids has an elevated white blood cell and neutrophil count. How can I tell if his elevated neutrophil count is caused by the corticosteroids or an acute infection?

The most helpful lab data favoring corticosteroid-induced granulocytosis (CIG) is the absence of a shift to the left in the peripheral WBC (ie, no more than 6% band forms) and toxic granulation.1 Although the total WBC itself is less helpful, experimental studies have reported a mean maximum neutrophil counts 2.4 times the base line after IV injection of hydrocortisone (200 mg) 2, and a mean increase of 4,000 neutrophils/mm3 after prednisone (20-80 mg). 3

Several possible mechanisms for CIG revolving around altered neutrophil characteristics and dynamics have been proposed4, including

  • Reduced egress from blood into tissues
  • Demargination from vascular endothelial surfaces
  • Delayed apoptosis
  • Enhanced release from the bone marrow.

An experimental animal study reported that only 10% of CIG is related to bone marrow release of neutrophils with the rest related to demargination (61%) and reduced egress from blood or delayed apoptosis (29%).4 This study may explain why high percentage of band forms would not be expected in CIG.

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References

  1. Shoenfeld Y, Gurewich Y, Gallant LA, et al. Prednisone-induced leukocytosis: influence of dosage, method, and duration of administration on the degree of leukocytosis. Am J Med 1981;71:773-78. Link
  2. Bishop CR, Athens JW, Boggs DR, et al. Leukokinetic studies: A non-steady-state kinetic evaluation of the mechanism of cortisone-induced granulocytosis. J Clin Invest 1986;47:249-60. https://www.ncbi.nlm.nih.gov/pubmed/5638121
  3. Dale DC, Fauci AS, Guerry DuPont, et al. Comparison of agents producing a neutrophilic leukocytosis in man. J Clin Invest 1975;56:808-13. PDF
  4. Nakagawa M, Terashma T, D’yachkova YD, et al. Glucocorticoid-induced granulocytosis: Contribution of marrow release and demargination of intravascular granulocytes. Circulation 1998;98:2307-13. PDF

 

 

My patient with COPD exacerbation on corticosteroids has an elevated white blood cell and neutrophil count. How can I tell if his elevated neutrophil count is caused by the corticosteroids or an acute infection?