Persistent Chronic Inflammation Contributes to the Development of Cancer in Patients with Rheumatoid Arthritis from a Defined Population of Northwestern Spain

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Objective

We assessed the contribution of clinical features, routine laboratory markers of inflammation, HLA-DRB1 alleles, and methotrexate therapy to cancer incidence and mortality in a cohort of rheumatoid arthritis (RA) patients prospectively followed at the single referral center for an area of Northwestern Spain.

Methods

Patients fulfilling the 1987 American College of Rheumatology classification criteria for RA seen at the rheumatology outpatient clinic of Hospital Xeral Calde, Lugo between March and September 1996 were included. HLA-DRB1 phenotype, epidemiological and clinical data from the time of RA diagnosis were assessed at that time. Afterward, patients were prospectively followed and clinical records were examined until the patient’s death or September 1, 2005. Presence of histologically confirmed diagnosis of cancer was assessed over the extended follow-up in all cases.

Results

One hundred eighty-two consecutive patients were assessed. Compared with the general Spanish population, the age- and gender-standardized mortality ratio for cancer was 1.01 (95% confidence interval: 0.49 to 1.75). Cancer mortality adjusted by age and sex was associated with chronic inflammation determined by C-reactive protein (CRP) (hazard ratio, HR, = 1.15; P < 0.001), and erythrocyte sedimentation rate (ESR) (HR = 1.05; P = 0.006). Increased risk of cancer was also associated with CRP (HR = 1.13; P = 0.001), ESR (HR = 1.04; P = 0.02), and the HLA-DRB1*0404 allele (HR = 3.24; P = 0.05).

Conclusion

This study does not support an increased mortality due to cancer in RA patients from Northwestern Spain. However, the present data indicate that high-grade inflammation contributes to both the risk and the mortality of cancer in RA.

Section snippets

Patients

Consecutive unselected patients who fulfilled the 1987 American College of Rheumatology (ACR) classification criteria for RA (21) seen at the rheumatology outpatient clinic of Hospital Xeral-Calde, Lugo (Northwestern Spain) between March and September 1996 were included in this study. This hospital is the single referral center for cancer and rheumatic diseases for a well-defined, stable, and ethnically homogenous, mixed rural and urban, white population living in central Galicia in

Results

One hundred eighty-two patients with RA were followed for 2447 person-years; mean follow-up from disease diagnosis was 13.4 years (median, 14 years, interquartile range [IQ range]: 10 to 16, range: 4 to 28). No patient was lost to follow-up. Most epidemiological and clinical data of this cohort of RA patients have recently been described (20). The mean age at disease onset (median [IQ range]) was 49.3 (50 [39 to 59]) years; the mean age at disease diagnosis was 54.1 (57 [46 to 64]) years, and

Discussion

In the Lugo region of Northwestern Spain the present study disclosed no increased cancer mortality in RA patients as compared with cancer mortality reported in the general population of Spain. Association between cancer and RA has been well documented in case reports, series reports, and epidemiological studies (1, 3, 5, 9, 30). Increased occurrence of malignancies such as Hodgkin’s, non-Hodgkin’s lymphoma, or multiple myeloma has been described in several cohort studies (4, 31, 32, 33, 34, 35,

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  • Cited by (0)

    1

    Drs. Gonzalez-Gay and Llorca share senior authorship in this study.

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