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Widespread body pain and mortality: prospective population based studyCommentary: An interesting finding, but what does it mean?

BMJ 2001; 323 doi: (Published 22 September 2001) Cite this as: BMJ 2001;323:662

Widespread body pain and cancer: caused by COX-2 overexpression?


Macfarlane et al have found an intriguing association between
widespread body pain and subsequent cancer mortality 1. We feel this
association is most likely to be due to biological factors rather than, as
suggested by the authors, psychosocial factors. We hypothesize that
enhanced activity of enzymes such as cyclooxygenase -2 (COX-2) may
underlie this association.

COX-2 overexpression is found in virtually all solid tumors including
lung, breast and gastrointestinal cancers. High tumour levels of COX-2 are
associated with poor prognosis. Recent studies indicate that COX-2 plays
an important role in the carcinogenic pathway of many malignancies. Hence
COX-2 is being targeted with selective inhibitors in cancer
chemoprevention studies 2 3.

The prostaglandins (PGs) are involved in the mediation of pain
pathways. PGs such as PGE2 are end products of COX-2 enzymatic action on
arachidonic acid. Induction of COX-2 and consequent augmentation of PGE2
production is associated with enhanced perception of pain 4 5.

Thus COX-2 overexpression may explain the association between
widespread body pain and cancer mortality.

Conflict of interest: None

Yours sincerely

Sundar Santhanam
Specialist registrar.

Ken O’Byrne
Senior lecturer.

Dept. of Oncology
Leicester Royal Infirmary
LE1 5WW.


1. Macfarlane GJ, McBeth J, Silman AJ, Crombie IK. Widespread body
pain and mortality: prospective population based study. BMJ 2001;323:662-

2. Dannenberg AJ, Altorki NK, Boyle JO, Dang C, Howe LR, Weksler BB,
et al. Cyclo-oxygenase 2: a pharmacological target for the prevention of
cancer. Lancet Oncology 2001;2(9):544-51.

3. O'Byrne KJ, Dalgleish AG. Chronic immune activation and
inflammation as the cause of malignancy. Br J Cancer 2001;85(4):473-83.

4. Yaksh TL, Dirig DM, Conway CM, Svensson C, Luo ZD, Isakson PC. The
acute antihyperalgesic action of nonsteroidal, anti-inflammatory drugs and
release of spinal prostaglandin E2 is mediated by the inhibition of
constitutive spinal cyclooxygenase-2 (COX-2) but not COX- 1. J Neurosci

5. Zhang Y, Shaffer A, Portanova J, Seibert K, Isakson PC. Inhibition
of cyclooxygenase-2 rapidly reverses inflammatory hyperalgesia and
prostaglandin E2 production. J Pharmacol Exp Ther 1997;283(3):1069-75.

Competing interests: No competing interests

04 October 2001
Sundar Santhanam
Specialist registrar
Dept of Oncology, Osborne Building, Leicester Royal Infirmary