Commentary on ‘Risk of colorectal cancer in women with pelvic inflammatory disease: a matched cohort study’
Numerous studies have documented an association between inflammatory bowel disease and colorectal cancer. The paper by Hsu and Lin in the current issue of BJOG is the first to purport an association between pelvic inflammatory disease (PID) and colorectal cancer risk.
How can we explain this association? Chlamydia is known to inhibit apoptosis (Fan et al. J Exp Med 1998;187:487–96). An obligate intracellular pathogen, Chlamydia has evolved strategies to protect its host cell against death-inducing stimuli to allow it to complete its lifecycle. Recent data suggest that Chlamydia-infected cells are able to resist apoptosis through stabilisation of the cellular protein hypoxia-inducible factor-1α (Sharma et al. Cell Microbiol 2011;13:1573–85). A cell protected from apoptosis has more opportunity to harbour genetic anomalies that subsequently predispose to tumorigenesis.
Beyond a possible role for Chlamydia, numerous biological mechanisms support the link between inflammation and cancer. In their seminal paper Hallmarks of cancer: the next generation, Hanahan and Weinberg postulated that inflammation facilitates tumorigenesis by delivering several bioactive molecules to the tumour microenvironment, including reactive oxygen species, growth factors, pro-angiogenic factors and extracellular matrix-modifying enzymes that assist tumour growth, angiogenesis, invasion and metastasis (Hanahan et al. Cell 2011;144:646–74).
It is therefore tempting to accept the association between PID and colorectal cancer documented by Hsu and Lin as fact. But before we start recommending colonoscopy for all women with a history of PID, we should scrutinise the data and be open minded to all possibilities.
The authors' decision to include women aged 13–45 years is unusual, especially as the incidence of colorectal cancer in women in their teens is extremely low. Some women were only followed up for a total period of 6 months, which is of course inadequate, particularly for the younger members of the cohort. The authors were also limited by the information held in the database. There was no information on potential confounding factors including body mass index, history of inflammatory bowel disease or genetic predisposition. In addition to flagging up an association between PID and colorectal cancer risk, the analysis also identified a number of somewhat surprising associations with PID, including statistically significant associations with congestive heart failure, peripheral vascular disease, cerebrovascular disease, chronic pulmonary disease, connective tissue disease, rheumatic disease, peptic ulcer disease, mild liver disease, diabetes without complications, paraplegia and hemiplegia, and renal disease. It is difficult to come up with a plausible biological mechanism that links all of these disparate diagnoses. Furthermore, if PID does predispose to cancer, one might intuitively expect that it would predispose to gynaecological cancer, as this is the primary site of infection, rather than colorectal cancer. The most likely explanation is that some other, unmeasured factor links PID and colorectal cancer in this cohort of women. We hope this paper stimulates further debate in this area.
Disclosure of interests
The authors have nothing to disclose.
EJ Crosbiea, E Buescherb, M Mahmoudb & F Nezhat
aUniversity of Manchester, Manchester, UK
bSt Luke's and Roosevelt Hospitals and Columbia University, New York, NY, USA