Elsevier

Mayo Clinic Proceedings

Volume 84, Issue 8, August 2009, Pages 685-693
Mayo Clinic Proceedings

ORIGINAL ARTICLE
Disease Associations With Monoclonal Gammopathy of Undetermined Significance: A Population-Based Study of 17,398 Patients

https://doi.org/10.4065/84.8.685Get rights and content

OBJECTIVE

To systematically study the association of monoclonal gammopathy of undetermined significance (MGUS) with all diseases in a population-based cohort of 17,398 patients, all of whom were uniformly tested for the presence or absence of MGUS.

PATIENTS AND METHODS

Serum samples were obtained from 77% (21,463) of the 28,038 enumerated residents in Olmsted County, Minnesota. Informed consent was obtained from patients to study 17,398 samples. Among 17,398 samples tested, 605 cases of MGUS and 16,793 negative controls were identified. The computerized Mayo Medical Index was used to obtain information on all diagnoses entered between January 1, 1975, and May 31, 2006, for a total of 422,663 person-years of observations. To identify and confirm previously reported associations, these diagnostic codes were analyzed using stratified Poisson regression, adjusting for age, sex, and total person-years of observation.

RESULTS

We confirmed a significant association in 14 (19%) of 75 previously reported disease associations with MGUS, including vertebral and hip fractures and osteoporosis. Systematic analysis of all 16,062 diagnostic disease codes found additional previously unreported associations, including mycobacterium infection and superficial thrombophlebitis.

CONCLUSION

These results have major implications both for confirmed associations and for 61 diseases in which the association with MGUS is likely coincidental.

Section snippets

PATIENTS AND METHODS

Details on assembly of the study cohort and testing for MGUS have been previously reported.1 Beginning with a list of all residents of Olmsted County, Minnesota, who were aged 50 years or older as of January 1, 1995, we obtained unused serum after routine clinical tests in the Mayo Clinic Laboratory Central Processing Area, which receives all serum samples from Mayo Clinic outpatients in Rochester, MN, as well as from patients at Mayo-affiliated Saint Marys and Rochester Methodist hospitals. A

RESULTS

The MGUS cohort consisted of 309 men and 296 women, with a mean age at diagnosis of 70 years (range, 39-99 years). Mean follow-up (ie, the first diagnosis date to the last) was 24 years (range, 0-31 years), for a total of 14,373 person-years. The serum M component was 12% IgA, 70% IgG, 15% IgM, and 3% biclonal, and the median M protein level was 0.5 g/dL. The controls consisted of 7520 men and 9273 women, with mean follow-up of 25 years (range, 0-30 years), for a total of 408,290 person-years.

DISCUSSION

Throughout the years, numerous diseases have been reported to be associated with MGUS.9 Because of the high prevalence of MGUS in the general population and the inherent bias of testing for MGUS only in patients with certain clinical symptoms, it is difficult to distinguish true pathogenetic relationships from coincidental associations. In fact, approximately 3% of patients with any given disease will be found to have MGUS based on coincidence. Therefore, the presence or absence of a true

CONCLUSION

Our study confirms several known associations of MGUS with disorders such as vertebral and hip fractures and osteoporosis, as well as provides a list of important new associations. It refutes the reported association of MGUS with numerous other disorders as likely coincidental, a finding that may have important therapeutic implications. The positive associations will be of value in the pathogenesis of myeloma, and they provide biologic insights into mechanisms of disease. The eAppendix that has

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    This study was supported in part by grants CA62242, CA107476, and AR30582 from the National Institutes of Health, US Public Health Service.

    This article is freely available on publication, because the authors have chosen the immediate access option.

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