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Risk of cancer among rheumatoid arthritis patients in California

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Abstract

Objective

The objective of this retrospective cohort study was to evaluate cancer risk among rheumatoid arthritis (RA) patients in California.

Methods

The study cohort derived from statewide patient discharge records was followed via linkage with cancer registry data over the period 1991–2002. Age and sex adjusted standardized incidence ratios (SIRs) and 95% confidence intervals were calculated to compare observed to expected numbers of cancers based on age, race, and sex specific incidence rates in the California population.

Results

Among the 84,475 RA patients, who were observed for 405,540 person-years, 5,533 incident cancers were diagnosed during the observation interval. The risk of developing lymphohematopoietic cancer was significantly higher in the cohort for both sexes. Males had significantly higher risks of lung, liver, and esophageal cancer, but a lower risk of prostate cancer. Females were at significantly decreased risk for several cancers including breast, ovary, uterus, cervix, and melanoma, with the risk reduction ranging from 15 to 57% lower than the general population. Hispanics had increased risks of leukemia, vagina/vulva, lung, and liver cancers.

Conclusion

Studies investigating the mechanisms that underlie the reported associations between RA and specific cancer types are needed.

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References

  1. Hochberg MC, Spector TD (1990) Epidemiology of rheumatoid arthritis: update. Epidemiol Rev 12:247–252

    PubMed  CAS  Google Scholar 

  2. Harris ED (1997) Clinical features of rheumatoid arthritis. In: Kelly WN, Harris ED, Ruddy S, Sledge CB (eds) Textbook of rheumatology, 5th edn. WB Saunders, Philadelphia, pp 895–922

    Google Scholar 

  3. Abu-Shakra M, Buskila D, Shoenfeld Y (2000) Rheumatoid arthritis and cancer. In: Gershwin ME, Shoenfeld Y (eds) Cancer and autoimmunity. Elsevier, Amsterdam, pp 19–30

  4. Isomaki HA, Hakulinene T, Joutsenlahti U (1978) Excess risk of lymphomas, leukemia and myeloma in patients with rheumatoid arthritis. J Chronic Dis 31:691–696. doi:10.1016/0021-9681(78)90071-1

    Article  PubMed  CAS  Google Scholar 

  5. Gridley G, McLaughlin JK, Ekbom A, Klareskog L, Adami H, Hacker DG et al (1993) Incidence of cancer among patients with rheumatoid arthritis. J Natl Cancer Inst 85:307–311. doi:10.1093/jnci/85.4.307

    Article  PubMed  CAS  Google Scholar 

  6. Katusic S, Beard CM, Kurland LT, Weis JW, Bergstralh (1985) Occurrence of malignant neoplasms in the Rochester, Minnesota, rheumatoid arthritis cohort. Am J Med 78(Suppl 1A):50–55. doi:10.1016/0002-9343(85)90246-3

    Article  PubMed  CAS  Google Scholar 

  7. Hakulinen T, Isomaki H, Knekt P (1985) Rheumatoid arthritis and cancer studies based on linking nationwide registries in Finland. Am J Med 78(suppl 1A):29–32. doi:10.1016/0002-9343(85)90242-6

    Article  PubMed  CAS  Google Scholar 

  8. Symmons DP, Ahern M, Bacon PA, Hawkins CF, Amlot PL, Jones EL et al (1984) Lymphoproliferative malignancy in rheumatoid arthritis: a study of 20 cases. Ann Rheum Dis 43:132–135. doi:10.1136/ard.43.2.132

    Article  PubMed  CAS  Google Scholar 

  9. Seidenfeld AM, Smythe HA, Ogryzlo MA, Urowitz MB, Dotten DA (1984) Acute leukemia in rheumatoid arthritis treated with cytotoxic agents. J Rheumatol 11:586–587

    PubMed  CAS  Google Scholar 

  10. Taylor HG, Nixon N, Sheeran TP, Dawes PT (1989) Rheumatoid arthritis and chronic lymphocytic leukemia. Clin Exp Rheumatol 7:529–532

    PubMed  CAS  Google Scholar 

  11. Fam AG, Lewis AJ, Cowan DH (1981) Multiple myeloma and amyloid bone lesions complicating rheumatoid arthritis. J Rheumatol 8:845–850

    PubMed  CAS  Google Scholar 

  12. Shenberger KN, Schned AR, Taylor TH (1984) Rheumatoid disease and bronchogenic carcinoma-case report and review of the literature. J Rheumatol 13:909–911

    Google Scholar 

  13. Gridley G, Klippel JH, Hoover RN, Fraumeni JF Jr (1994) Incidence of cancer among men with the Felty syndrome. Ann Intern Med 120(1):35–39

    PubMed  CAS  Google Scholar 

  14. Cibere J, Sibley J, Haga M (2001) Systemic lupus erythematosus and the risk of malignancy. Lupus 10(6):394–400. doi:10.1191/096120301678646128

    Article  PubMed  CAS  Google Scholar 

  15. Kauppi M, Isomaki H (1997) Elevated incidence of hematologic malignancies in patients with Sjogren’s syndrome compared with patients with rheumatoid arthritis. Cancer Causes Control 1997:201–204

    Article  Google Scholar 

  16. Thun MJ, Nambodiri MM, Heathn CW Jr (1991) Aspirin use and reduced risk of fatal colon cancer. N Engl J Med 325:1593–1596

    PubMed  CAS  Google Scholar 

  17. Askling J, Baecklund E, Granath F, Geborek P, Fored M, Backlin C, et al. (2008) Anti-TNF therapy in RA and risk of malignant lymphomas relative risks and time-trends in the Swedish Biologics Register. Ann Rheum Dis

  18. Baecklund E, Askling J, Rosenquist R, Ekbom A, Klareskog L (2004) Rheumatoid arthritis and malignant lymphomas. Curr Opin Rheumatol 16(3):254–261. doi:10.1097/00002281-200405000-00014

    Article  PubMed  Google Scholar 

  19. Baecklund E, Iliadou A, Askling J, Ekbom A, Backlin C, Granath F et al (2006) Association of chronic inflammation, not its treatment, with increased lymphoma risk in rheumatoid arthritis. Arthritis Rheum 54(3):692–701. doi:10.1002/art.21675

    Article  PubMed  Google Scholar 

  20. Kinlen LJ (1992) Malignancy in autoimmune diseases. J Autoimmun 5(Suppl A):363–371. doi:10.1016/0896-8411(92)90055-U

    Article  PubMed  Google Scholar 

  21. Silman AJ, Petrie J, Hazleman B, Evans SJ (1988) Lymphoproliferative cancer and other malignancy in patients with rheumatoid arthritis treated with azathioprine: a 20 year follow up study. Ann Rheum Dis 47:988–992. doi:10.1136/ard.47.12.988

    Article  PubMed  CAS  Google Scholar 

  22. Tennis P, Andrews E, Bombardier C, Wang Y, Strand L, West R et al (1993) Record linkage to conduct an epidemiologic study on the association of rheumatoid arthritis and lymphoma in the province of Saskatchewan, Canada. J Clin Epidemiol 46(7):685–695. doi:10.1016/0895-4356(93)90049-7

    Article  PubMed  CAS  Google Scholar 

  23. Services USDoHaH (ed) (2000) ICD-9-CM: international classification of diseases, 9th revision, clinical modification, 6th edn. Washington, DC

  24. Cancer Reporting in California: Standards for Automated Reporting (1997) California cancer reporting system standards, vol II. California Department of Health Services, Cancer Surveillance Section, Sacramento, CA

  25. Cancer Reporting in California: Data Standards for Regional Registries and California Cancer Registry (1997) California cancer reporting system standards, vol III. California Department of Health Services, Cancer Surveillance Section, Sacramento, CA

  26. Cancer Reporting in California: Reporting Procedures for Physicians (1998) California cancer reporting system standards, vol IV. California Department of Health Services, Cancer Surveillance Section, Sacramento, CA

  27. Cancer Reporting in California: Abstracting and Coding Procedures for Hospitals (1997) California cancer reporting system standards, vol I. California Department of Health Services, Cancer Surveillance Section, Sacramento, CA

  28. Chen VW, Howe HL, Wu XC (2000) Cancer in North America, 1993–1997 vol I. Incidence. North American Association of Central Cancer Registries, Springfield, IL

  29. Seiffert JE, Price WT, Gordon B (1990) The California tumor registry: a state-of-the-art model for a regionalized, automated, population-based registry. Top Health Rec Manage 11:59–73

    PubMed  CAS  Google Scholar 

  30. Vality Technology Inc. (1999) Integrity program: data reengineering environment software, ver 3.3. Vality Technology Inc., Boston, MA

  31. Allen M (2001) Validation of OSHPD and CCR insurance status. In: California association of central cancer registries technical conference, 25 September, 2001, Riverside, CA

  32. Breslow NE, Day NE (1987) Statistical methods in cancer research. Vol II. The design and analysis of cohort studies. International Agency for Research on Cancer, Lyon

  33. Mellemkjaer L, Linet MS, Gridley G, Frisch M, Moller H, Olsen JH (1996) Rheumatoid arthritis and cancer risk. Eur J Cancer 32A(10):1753–1757. doi:10.1016/0959-8049(96)00210-9

    Article  PubMed  CAS  Google Scholar 

  34. Prior P (1985) Cancer and rheumatoid arthritis: epidemiologic considerations. Am J Med 78(Suppl 1A):15–21. doi:10.1016/0002-9343(85)90240-2

    Article  PubMed  CAS  Google Scholar 

  35. Thomas E, Brewster DH, Black RJ, Macfarlane GJ (2000) Risk of malignancy among patients with rheumatic conditions. Int J Cancer 88(3):497–502. doi:10.1002/1097-0215(20001101)88:3<497::AID-IJC27>3.0.CO;2-J

    Article  PubMed  CAS  Google Scholar 

  36. Baecklund E, Ekbom A, Sparen P, Feltelius N, Klareskog L (1998) Disease activity and risk of lymphoma in patients with rheumatoid arthritis: nested case–control study. Br Med J 317(7152):180–181

    CAS  Google Scholar 

  37. Wolfe F (1998) Inflammatory activity but not prednisone or methotrexate use predicts non-Hodgkin’s lymphoma in rheumatoid arthritis: a 25-year study of 1,767 RA patients [abstract 931]. Arthritis Rheum S188

  38. Baker GL, LE Kahl, Zee BC, Stolzer BL, Agarwal AK, Medsger TA Jr (1987) Malignancy following treatment of rheumatoid arthritis with cyclophosphamide. Long-term case–control follow-up study. Am J Med 83(1):1–9. doi:10.1016/0002-9343(87)90490-6

    Article  PubMed  CAS  Google Scholar 

  39. Kinlen LJ (1985) Incidence of cancer in rheumatoid arthritis and other disorders after immunosuppressive treatments. Am J Med 78(suppl 1A):44–49. doi:10.1016/0002-9343(85)90245-1

    Article  PubMed  CAS  Google Scholar 

  40. Matteson EL, Hickey AR, Maguire L, Tilson HH, Urowitz MB (1991) Occurrence of neoplasia in patients with rheumatoid arthritis enrolled in a DMARD registry. Rheumatoid arthritis azathioprine registry steering committee. J Rheumatol 8(6):809–814

    Google Scholar 

  41. Radis CD, Kahl LE, Baker GL, Wasko MC, Cash JM, Gallatin A et al (1995) Effects of cyclophosphamide on the development of malignancy and on long-term survival of patients with rheumatoid arthritis. A 20-year followup study. Arthritis Rheum 38(8):1120–1127. doi:10.1002/art.1780380815

    Article  PubMed  CAS  Google Scholar 

  42. Bongartz T, Sutton AJ, Sweeting MJ, Buchan I, Matteson EL, Montori V (2006) Anti-TNF antibody therapy in rheumatoid arthritis and the risk of serious infections and malignancies: systematic review and meta-analysis of rare harmful effects in randomized controlled trials. JAMA 295(19):2275–2285. doi:10.1001/jama.295.19.2275

    Article  PubMed  CAS  Google Scholar 

  43. Beauparlant P, Papp K, Haraoui B (1999) The incidence of cancer associated with the treatment of rheumatoid arthritis. Semin Arthritis Rheum 29:148–158. doi:10.1016/S0049-0172(99)80026-2

    Article  PubMed  CAS  Google Scholar 

  44. Starkebaum G (2001) Rheumatoid arthritis, methotrexate, and lymphoma: risk substitution, or cat and mouse with Epstein-Barr virus? J Rheumatol 28(12):2573–2575

    PubMed  CAS  Google Scholar 

  45. Helmers R, Galvin J, Hunninghake GW (1991) Pulmonary manifestations associated with rheumatoid arthritis. Chest 100(1):235–238. doi:10.1378/chest.100.1.235

    Article  PubMed  CAS  Google Scholar 

  46. Hernandez Avila M, Liang MH, Willett WC, Stampfer MJ, Colditz GA, Rosner B et al (1990) Reproductive factors, smoking, and the risk for rheumatoid arthritis. Epidemiology 1(4):285–291

    Article  PubMed  CAS  Google Scholar 

  47. Silman AJ, Newman J, MacGregor AJ (1996) Cigarette smoking increases the risk of rheumatoid arthritis. Results from a nationwide study of disease-discordant twins. Arthritis Rheum 39(5):732–735. doi:10.1002/art.1780390504

    Article  PubMed  CAS  Google Scholar 

  48. Voigt LF, Koepsell TD, Nelson JL, Dugowson CE, Daling JR (1994) Smoking, obesity, alcohol consumption, and the risk of rheumatoid arthritis. Epidemiology 5(5):525–532

    PubMed  CAS  Google Scholar 

  49. Baron JA (2003) Epidemiology of non-steroidal anti-inflammatory drugs and cancer. Prog Exp Tumor Res 37:1–24. doi:10.1159/000071364

    Article  PubMed  CAS  Google Scholar 

  50. Chakravarty EF, Genovese MC (2004) Associations between rheumatoid arthritis and malignancy. Rheum Dis Clin North Am 30(2):271–284. doi:10.1016/j.rdc.2004.01.007 Vi

    Article  PubMed  Google Scholar 

  51. Buchbinder R, Barber M, Heuzenroeder L, Wluka AE, Giles G, Hall S et al (2008) Incidence of melanoma and other malignancies among rheumatoid arthritis patients treated with methotrexate. Arthritis Rheum 59(6):794–799. doi:10.1002/art.23716

    Article  PubMed  CAS  Google Scholar 

  52. Abasolo L, Judez E, Descalzo MA, Gonzalez-Alvaro I, Jover JA, Carmona L (2008) Cancer in rheumatoid arthritis: occurrence, mortality, and associated factors in a South European population. Semin Arthritis Rheum 37(6):388–397. doi:10.1016/j.semarthrit.2007.08.006

    Article  PubMed  Google Scholar 

  53. Gao J, Niwa K, Sun W, Takemura M, Lian Z, Onogi K et al (2004) Non-steroidal anti-inflammatory drugs inhibit cellular proliferation and upregulate cyclooxygenase-2 protein expression in endometrial cancer cells. Cancer Sci 95(11):901–907. doi:10.1111/j.1349-7006.2004.tb02200.x

    Article  PubMed  CAS  Google Scholar 

  54. Gonzalez-Perez A, Garcia Rodriguez LA, Lopez-Ridaura R (2003) Effects of non-steroidal anti-inflammatory drugs on cancer sites other than the colon and rectum: a meta-analysis. BMC Cancer 3:28. doi:10.1186/1471-2407-3-28

    Article  PubMed  Google Scholar 

  55. Mahmud SM, Tanguay S, Begin LR, Franco EL, Aprikian AG (2006) Non-steroidal anti-inflammatory drug use and prostate cancer in a high-risk population. Eur J Cancer Prev 15(2):158–164. doi:10.1097/01.cej.0000197451.02604.25

    Article  PubMed  CAS  Google Scholar 

  56. Moorman PG, Grubber JM, Millikan RC, Newman B (2003) Association between non-steroidal anti-inflammatory drugs (NSAIDs) and invasive breast cancer and carcinoma in situ of the breast. Cancer Causes Control 14(10):915–922. doi:10.1023/B:CACO.0000007973.59863.66

    Article  PubMed  Google Scholar 

  57. Pereg D, Lishner M (2005) Non-steroidal anti-inflammatory drugs for the prevention and treatment of cancer. J Intern Med 258(2):115–123. doi:10.1111/j.1365-2796.2005.01519.x

    Article  PubMed  CAS  Google Scholar 

  58. Stock DC, Groome PA, Siemens DR, Rohland SL, Song Z (2008) Effects of non-selective non-steroidal anti-inflammatory drugs on the aggressiveness of prostate cancer. Prostate

  59. Cevik R, Em S, Gur A, Nas K, Sarac AJ, Colpan L (2004) Sex and thyroid hormone status in women with rheumatoid arthritis: are there any effects of menopausal state and disease activity on these hormones? Int J Clin Pract 58(4):327–332. doi:10.1111/j.1368-5031.2004.00005.x

    Article  PubMed  CAS  Google Scholar 

  60. Cutolo M, Villaggio B, Craviotto C, Pizzorni C, Seriolo B, Sulli A (2002) Sex hormones and rheumatoid arthritis. Autoimmun Rev 1(5):284–289. doi:10.1016/S1568-9972(02)00064-2

    Article  PubMed  CAS  Google Scholar 

  61. Kuiper S, van Gestel AM, Swinkels HL, de Boo TM, da Silva JA, van Riel PL (2001) Influence of sex, age, and menopausal state on the course of early rheumatoid arthritis. J Rheumatol 28(8):1809–1816

    PubMed  CAS  Google Scholar 

  62. Masi AT (1995) Sex hormones and rheumatoid arthritis: cause or effect relationships in a complex pathophysiology? Clin Exp Rheumatol 13(2):227–240

    PubMed  CAS  Google Scholar 

  63. Katz JN, Barrett J, Liang MH, Bacon AM, Kaplan H, Kieval RI et al (1997) Sensitivity and positive predictive value of medicare part B physician claims for rheumatologic diagnoses and procedures. Arthritis Rheum 40(9):1594–1600. doi:10.1002/art.1780400908

    Article  PubMed  CAS  Google Scholar 

  64. Brooks PM (1992) Rheumatic manifestations of neoplasia. Curr Opin Rheumatol 4(1):90–93

    PubMed  CAS  Google Scholar 

  65. Butler RC, Thompson JM, Keat AC (1987) Paraneoplastic rheumatic disorders: a review. J R Soc Med 80(3):168–172

    PubMed  CAS  Google Scholar 

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Acknowledgment

This work was funded by grant 1R21CA100759-01A2 from the National Cancer Institute. The collection of cancer incidence data used in this study was supported by the California Department of Health Services as part of the statewide cancer reporting program mandated by California Health and Safety Code Section 103885; the National Cancer Institute’s Surveillance, Epidemiology and End Results Program under contract N01-PC-35136 awarded to the Northern California Cancer Center, contract N01-PC-35139 awarded to the University of Southern California, and contract N02-PC-15105 awarded to the Public Health Institute; and the Centers for Disease Control and Prevention’s National Program of Cancer Registries, under agreement #U55/CCR921930-02 awarded to the Public Health Institute.

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The ideas and opinions expressed herein are those of the author(s) and endorsement by the State of California, Department of Health Services, the National Cancer Institute, and the Centers for Disease Control and Prevention or their Contractors and Subcontractors is not intended nor should be inferred.

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Correspondence to Arti Parikh-Patel.

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Parikh-Patel, A., White, R.H., Allen, M. et al. Risk of cancer among rheumatoid arthritis patients in California. Cancer Causes Control 20, 1001–1010 (2009). https://doi.org/10.1007/s10552-009-9298-y

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