The relationship between the presence and site of cancer, an inflammation-based prognostic score and biochemical parameters. Initial results of the Glasgow Inflammation Outcome Study

Abstract

Background: Cancer incidence is increasing in the United Kingdom, as well as on a global basis. Biochemical parameters, such as C-reactive protein and albumin (combined to form the modified Glasgow Prognostic Score, mGPS), alkaline phosphatase (Alk phos), gamma-glutamyl transferase (GGT) and serum calcium have been reported to be associated with cancer and non-cancer mortality. Therefore, to definitively examine the interrelationships between the above biochemical parameters, the mGPS and the presence of cancer, the Glasgow Inflammation Outcome Study was undertaken. The aim of this initial study was to examine the effect of cancer on markers of systemic inflammation induced by the liver (mGPS) and on levels of routine biochemical parameters.

Methods: Patients (n=223 303) who had a single incidental sample taken for C-reactive protein, albumin, calcium and serum liver function tests where available, between 2000 and 2008 were studied. Those with a pathological diagnosis of cancer (n=22 715) were identified. The mGPS was constructed and liver function tests classified in accordance with the local reference ranges.

Results: Patients with cancer had higher C-reactive protein and lower albumin levels (and thus a higher mGPS), higher adjusted calcium, Alk phos and GGT levels, but lower aspartate transaminase (AST) and alanine transaminase (ALT) levels (all P<0.001). The strongest associations (Spearman's correlation > or =0.3) in both the non-cancer and cancer groups were found between albumin, C-reactive protein and Alk phos, AST and ALT, AST and GGT and ALT and GGT (all P<0.001). On multivariate analysis, the associations with the presence of cancer remained with age, deprivation, C-reactive protein, albumin, adjusted calcium, Alk phos and GGT (all P<0.01). Patients following a diagnosis of cancer had lower albumin levels and thus higher mGPS (all P<0.001). Also, post-diagnosis patients were more likely to have lower adjusted calcium, bilirubin, Alk Phos, AST, ALT and GGT levels (all P<0.05). When the cancer diagnoses were ranked from those with the lowest proportion of mGPS 1 or 2 to those with the highest, the percentage of cases with a mGPS of 1 or 2 ranged from 21% in breast cancer to 46% in prostate cancer and to 68% in pulmonary cancer. Compared with breast cancer the mGPS was significantly higher in those diagnosed with dermatological, bladder, endocrinological, gynaecological, prostate, musculoskeletal, gastroesophageal, haematological, renal, colorectal, head and neck, pancreaticobiliary and pulmonary cancers (all P<0.001).

Conclusion: The results of the present study indicate that the systemic inflammatory response is common in a large patient cohort, increased by the presence of cancer and associated with the perturbation of a number of biochemical parameters previously reported to be associated with mortality. There is a striking parallel between the proportions of cases with a mGPS of 1 or 2 and reported survival rates in these tumours.