To the editor:
Recent data suggest that the incidence of multiple myeloma may be increasing in Taiwan over the past 25 years,1 which elevates concern that myeloma incidence may be increasing in Asia. If true, this may reflect changes in lifestyle, occupational and environmental exposures, and food intake among other factors, between the younger and older birth cohorts. However, this observation could also be indicative of differences in access to health care, improvement in diagnostic techniques, data collection method, and other influences unrelated to biology.
Based on a large prospective cancer-screening trial (N = 77 469), we have shown that multiple myeloma is consistently preceded by a precursor state: monoclonal gammopathy of undetermined significance (MGUS).2 To address the question of whether multiple myeloma is becoming increasingly more common in Asia, and to overcome the above-mentioned potential bias due to factors unrelated to biology, we conducted a population-screening study to determine the prevalence of MGUS in an ethnically Chinese population.
Plasma from 500 male and 500 female volunteer donors 50 years of age or older (median, 57 years; range, 50-65 years) was collected following a uniform protocol at the Hong Kong Red Cross Blood Transfusion Service from December 2008 to January 2009. Using serum protein electrophoresis (SPEP) (Helena SPIFE 3000; Helena Laboratories, Beaumont, TX) and κ and λ free light chain (FLC) assays (SPA-Plus; The Binding Site, Birmingham, United Kingdom), we assessed for evidence of monoclonal (M) proteins and abnormal FLC ratios (normal reference, 0.26-1.65) for all patients. Patients with an abnormal FLC ratio and/or suspicious SPEP (28 male, 10 female) were subjected to immunofixation electrophoresis.
Among screened subjects we found that 6 of 500 men (1.2%) and 2 of 500 women (0.4%) had MGUS; overall, this represents a prevalence of 0.8% (95% confidence interval [CI]: 0.3%-1.4%). All study subjects had an immunoglobulin G (IgG) isotype monoclonal band except for 2 individuals: 1 with IgA and another with biclonal IgG (Table 1).
Study subjects with evidence of an M protein
| Patient no. . | Sex . | Age, y . | M-protein isotype . | M-protein concentration, g/dL . | Free κ, mg/dL . | Free λ, mg/dL . | FLC ratio . |
|---|---|---|---|---|---|---|---|
| 1 | F | 59 | IgG κ | 0.22 | 6.76 | 11.05 | 0.61 |
| 2 | F | 53 | IgG λ | 0.60 | 8.65 | 12.24 | 0.71 |
| 3 | M | 50 | IgG κ | 0.54 | 15.09 | 11.46 | 1.32 |
| 4 | M | 54 | IgG κ | 0.39 | 21.76 | 14.91 | 1.46 |
| 5 | M | 54 | Biclonal (IgG κ and IgG λ) | 0.57, 0.62 | 14.09 | 11.59 | 1.22 |
| 6 | M | 53 | IgG λ | 1.45 | 6.28 | 285.64 | 0.02 |
| 7 | M | 56 | IgA κ | 1.89 | 18.64 | 11.26 | 1.66 |
| 8 | M | 56 | IgG λ | 0.47 | 6.14 | 11.63 | 0.53 |
| Patient no. . | Sex . | Age, y . | M-protein isotype . | M-protein concentration, g/dL . | Free κ, mg/dL . | Free λ, mg/dL . | FLC ratio . |
|---|---|---|---|---|---|---|---|
| 1 | F | 59 | IgG κ | 0.22 | 6.76 | 11.05 | 0.61 |
| 2 | F | 53 | IgG λ | 0.60 | 8.65 | 12.24 | 0.71 |
| 3 | M | 50 | IgG κ | 0.54 | 15.09 | 11.46 | 1.32 |
| 4 | M | 54 | IgG κ | 0.39 | 21.76 | 14.91 | 1.46 |
| 5 | M | 54 | Biclonal (IgG κ and IgG λ) | 0.57, 0.62 | 14.09 | 11.59 | 1.22 |
| 6 | M | 53 | IgG λ | 1.45 | 6.28 | 285.64 | 0.02 |
| 7 | M | 56 | IgA κ | 1.89 | 18.64 | 11.26 | 1.66 |
| 8 | M | 56 | IgG λ | 0.47 | 6.14 | 11.63 | 0.53 |
These results are based on screening of 500 men and 500 women (50 years of age or older) in an ethnically Chinese population in Hong Kong, and support the fact that Chinese individuals in Hong Kong have lower incidence of MGUS than whites. The minimal number of samples required to distinguish 0.8% (our study proportion) from 3% (lower bound of reported prevalence of MGUS in whites7 ) is 448 (power [β] = 90%; specificity [α] = 95% 2-tailed; test: 1-sample χ2).
To our knowledge, our study represents the first larger, prospective population-screening study of MGUS in ethnically Chinese persons. Our findings are consistent with older studies showing that Asians have a fivefold lower incidence of multiple myeloma compared with whites,3 and are consistent with prior MGUS prevalence studies in Thailand (2.3%; 95% CI, 1.1%-4.6%),4 Korea (3.3%; 95% CI, 1.0%-4.2%),5 and Japan (2.1%; 95% CI, 1.9%-2.2%).6 In the Olmsted County study conducted by the Mayo Clinic, the prevalence of MGUS among 50- to 59-year-old and 60- to 69-year-old whites was 1.6% and 3.0%, respectively.7 Although the number of index cases in our study is low, the gender ratio is also well maintained. We speculate that underlying mechanisms accounting for the variance in prevalence of MGUS and multiple myeloma among different ethnic groups is most likely due to differences in germline genes, environmental exposures, and lifestyle.8
The large, aging population of China urgently needs data on the possible future incidence of multiple myeloma. Our results support the hypothesis that a lower incidence of multiple myeloma in ethnic Chinese people is maintained at early disease initiation and not due to different rates of disease progression. The lifestyle and economic status of various screened Asian populations are not uniform and such observation comes from a highly Westernized and developed population of ethnic Chinese individuals.
Authorship
S.P.W. and A.M. contributed equally to the work.
Acknowledgments: This work was supported by the Intramural Research Program of the National Cancer Institute of the National Institutes of Health (NIH) and the NIH Medical Research Scholars Program. Donated plasma from the study individuals was used for the study as per standard approval of Hong Kong Red Cross Blood Transfusion Service.
The study was approved by institutional review boards at Queen Mary Hospital. This study was exempt from institutional review, board review, and informed consent as per the National Institutes of Health Office of Human Subjects Research because it analyzed existing samples and data stripped of personal identifiers and there was no patient contact.
Contribution: S.P.W. analyzed data and drafted the report; A.M., R.C., and A.Z. designed research, processed samples, and ran arrays; C.-K.L. and W.-Y.A. enrolled patients and designed research; O.L. designed the research, analyzed data, and drafted the report; and all authors reviewed the manuscript, gave input, and approved the final version.
Conflict-of-interest disclosure: The authors declare no competing financial interests.
Correspondence: Ola Landgren, Multiple Myeloma Section, Metabolism Branch, National Cancer Institute, National Institutes of Health, 9000 Rockville Pike, Building 10/Room 13N240, Bethesda, MD 20892; e-mail: landgreo@mail.nih.gov.
