Cigarette smoking and rheumatoid arthritis*,**

https://doi.org/10.1053/sarh.2001.27719Get rights and content

Abstract

Objectives: To examine and explore the potential relationships among the following: the incidence/severity of rheumatoid arthritis (RA), the extra-articular manifestations of RA, vascular disease, certain specific malignancies, the p53 tumor suppressor gene, and cigarette smoking. Methods: The medical literature was reviewed from 1985 to 2001 with the assistance of a MEDLINE search using the key words vascular disease, smoking, protein p53, RA, rheumatoid vasculitis, cancer, and malignancies. A qualitative review was performed after all articles were abstracted and new information summarized. Results: Cigarette smoking has been increasingly shown in epidemiologic and case-control studies to be an important risk factor for both the incidence and severity of RA, especially in seropositive men. Further, there is evidence of a downward trend in incidence of extra-articular manifestations of RA, especially RA vasculitis, observed with a decrease in worldwide tobacco use and overall improved mortality in RA. The association of cigarette smoking with lung and other cancers and its link to vascular disease (including Buerger's disease) and atherosclerosis appears secure. Mutations or alterations in p53, a suppressor gene that regulates cell growth, have been found in certain cancers, cigarette smokers, and in patients with RA. Conclusions: Cigarette smoking appears to have an undeniable link to the pathogenesis of vascular disease of many types, including the possibility of a strong causal connection to rheumatoid vasculitis. The observations worldwide of decreasing tobacco use along with secular trends of diminished RA vasculitis and extra-articular manifestations, and with improved survival, points to a better outcome for our patients. The example of p53 may be a first step in the discovery of additional links between environmental triggers and phenotypic expression of chronic illness. Semin Arthritis Rheum 31:146-159. Copyright © 2001 by W.B. Saunders Company

Section snippets

Methods

The hypothesis for this review was the potential existence of a relationship among RA, vascular disease, smoking, p53, and malignancy. Therefore, a MEDLINE and PubMed search of the medical literature was carried out with the key words and MESH headings of rheumatoid arthritis, smoking, vascular disease, vasculitis, rheumatoid vasculitis, malignancy, protein p53, and cancer. A qualitative review of the articles obtained was undertaken, and each paper was examined for possible relationships

Gene p53 and cancer

The p53 tumor suppressor gene encodes a 53 kDa nuclear phosphoprotein that plays a major role in the synthesis, repair, and apoptotic functions of the cell cycle 11, 29. These mechanisms have likely evolved to maintain the stability of the genome during cellular stress from DNA damage, hypoxia, and activated oncogenes. When cellular DNA is damaged, the p53 protein arrests growth at the G1/S interface until the damage is repaired. Alternatively, p53 will induce apoptosis if damage is severe (30)

Discussion

The undeniable role cigarette smoking plays in the pathogenesis of vascular disease and cancer has paved the way for its recognition as a risk factor for either incidence or severity in RA. Figure 1 symbolizes potential interrelationships among smoking and various individual molecular mechanisms and disease processes.

. Hypothetical relationships with cigarette smoking among disease expression, molecular mechanisms, and disease pathogenesis.

Damage induced by NO, oxygen radicals, and carbon

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    *

    Shirley A. Albano, MD: Fellow, Division of Rheumatology, Cedars-Sinai Medical Center, Los Angeles, CA; Ernesto Santana-Sahagun, MD: Clinical Assistant Professor of Medicine, UCSD School of Medicine, La Jolla, CA; and Michael H. Weisman, MD: Director, Division of Rheumatology, Cedars Sinai Medical Center, Los Angeles, CA, and Professor of Medicine, UCLA School of Medicine, Los Angeles, CA.

    **

    Address reprint requests to Michael H. Weisman, MD, Cedars-Sinai Medical Center, 8700 Beverly Blvd, B-131, Los Angeles, CA 90048. E-mail: [email protected]

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    Copyright © 2001 W.B. Saunders Company. Published by Elsevier Inc. All rights reserved.