pmc.ncbi.nlm.nih.gov

Racial Disparities in the Prevalence of Monoclonal Gammopathies: A population-based study of 12,482 persons from the National Health and Nutritional Examination Survey

  • ️Fri Dec 19 2008

. Author manuscript; available in PMC: 2014 Jul 9.

Published in final edited form as: Leukemia. 2014 Jan 20;28(7):1537–1542. doi: 10.1038/leu.2014.34

Abstract

Background

The incidence of multiple myeloma (MM) is markedly higher in blacks compared with whites. This may be related to a higher prevalence of monoclonal gammopathy of undetermined significance (MGUS), the premalignant lesion that precedes MM. Our objective was to define the prevalence and risk factors of MGUS in blacks, Hispanics, and whites using a large cohort representative of the United States (U.S.) population.

Methods

Of 13,278 adults age ≥50 years enrolled in National Health and Nutritional Examination Survey (NHANES) III or NHANES 1999–2004, stored serum samples to test for monoclonal proteins were available on 12,482 persons (2,331 non-Hispanic blacks considered “black”, 2,475 Hispanics, 7,051 non-Hispanic whites considered “white”, and 625 “others”). Agarose-gel electrophoresis, serum protein immunofixation, serum free light-chain assay, and typing of the M-protein was performed on sera from all subjects. Unadjusted and adjusted prevalence rates were computed from logistic regression analysis. Risk factors were studied using available survey information available from NHANES. Main outcomes and measures were prevalence of MGUS by age, gender, race, ethnicity, and risk factors from available survey information.

Findings

MGUS was identified in 365 participants, for an overall prevalence of 2.4%. Adjusted prevalence of MGUS was significantly higher (p<0.001) in blacks (3.7%) compared with whites (2.3%) (p=0.001) or Hispanics (1.8%). MGUS in blacks had characteristics that posed a greater risk of progression to MM. The prevalence of MGUS (adjusted for age, education, sex, race, smoking) was 3.1% and 2.1% for the North and Midwest versus South and West regions of the U.S., respectively (p=0.052).

Interpretation

MGUS is significantly more common in blacks, and more often has features associated with higher risk of progression to MM. We also find a strong geographic disparity in the prevalence of MGUS between the North/Midwest versus the South/West regions of the U.S., which has etiologic implications.

Keywords: monoclonal gammopathy, prevalence, prognosis, biomarker, racial disparity

INTRODUCTION

Multiple myeloma (MM) is a fatal B-cell dysplasia characterized by plasma cell infiltration in the bone marrow and a monoclonal immunoglobulin (M-protein) in serum, urine or both.1 MM is almost always preceded by the premalignant state, monoclonal gammopathy of undetermined significance (MGUS),2,3 which is characterized by the presence of an M-protein without evidence of MM or related disorder.4 MGUS is associated with a relentless risk of progression to MM or related malignancy, at a rate of 1% per year.5 The risk is higher in those with high-risk biomarkers. Patients with an abnormal serum free light-chain (FLC) ratio, non-IgG MGUS and a high serum M-protein level (≥1.5 g/dL) have a 58% absolute risk of developing MM over a 20-year-period.6

There is a marked racial disparity in the incidence of MM.7 African-Americans have a twofold or greater risk of MM compared with whites.8 The higher incidence of MM in blacks is may result from a higher prevalence of the precursor lesion, MGUS, or an increased risk of progression of MGUS to MM.9,10 So far, accurate estimates of the prevalence of MGUS in blacks and whites from a representative sample of the entire U.S. are not available. Since MM is a devastating malignancy, a better understanding of the reasons for the racial disparity in incidence is of critical importance.

The largest population-based study of MGUS so far comes from the relatively homogenous white population living in Olmsted County, Minnesota, where the prevalence of MGUS was estimated at 3.2% of the population ≥50 years of age,11,5 but data are needed on the prevalence of MGUS in blacks and Hispanics, as well as whites from other regions of the U.S. Further, data on risk factors associated with the occurrence of MGUS across the racial groups are required in order to determine optimal screening and preventive strategies. In this study, we utilized samples and data from the National Health and Nutritional Examination Survey (NHANES), a nationally representative sample of the U.S. population, to answer these important questions. We used sensitive laboratory techniques to determine the prevalence of MGUS, and studied the association of MGUS with baseline variables collected through NHANES.

METHODS

Study population and serum samples

The data for this paper come from NHANES III (1988–1994) and NHANES (1999–2004), which are population-based cross-sectional surveys consisting of in-person home interviews and medical examinations conducted by the Centers for Disease Control and Prevention (CDC) to assess the health and nutritional status of adults and children in the U.S.12,13 Participant identification is based on a stratified multistage complex sample design to select a nationally representative sample of the civilian, non-institutionalized U.S. population, with oversampling (higher sampling rates) of older adults and non-Hispanic blacks and Mexican-Americans, and other groups. Survey data, including demographics, health status, health disorders, and behaviors, etc., are collected by household interviews. Physical examinations and blood collection occur at a mobile examination center by phlebotomists.

Testing for monoclonal proteins

Testing for the presence of MGUS was performed at the Protein Immunology Laboratory, Mayo Clinic, Rochester, Minnesota, using laboratory techniques that have been well described previously.6,11 Briefly, conventional agarose-gel electrophoresis was performed on sera from all subjects. Samples with an equivocal or definite M-protein present on electrophoresis were then subjected to serum protein immunofixation, and serum free light-chain assay for confirmation and typing of the M-protein. All testing and interpretation was done by individuals blinded to all demographic and other details pertaining to the samples being tested.

Prevalence estimates and risk factors

Once testing was completed, data were transferred to the National Center for Health Statistics for linking to the NHANES Public Use files that contain the serologic and demographic data needed for these analyses. Once the MGUS data were released to the public on the NHANES web site, the data could be analyzed by the National Cancer Institute. The prevalence of MGUS was estimated in the total population, as well as for whites, blacks, and Mexican-Americans separately, and by age, gender, and other known risk factors.

Statistical Analysis

Prevalence rates were calculated by dividing the weighted number of persons with MGUS from the sample by the weighted number of total persons (with or without MGUS). Adjusted prevalence rates were computed from logistic regression analysis where confounders such as age, gender, and smoking were included in the models.14 Wald F-tests, which take account of the complex design of NHANES, were used to test hypotheses regarding the estimated prevalence of MGUS. Restricted cubic spline regression in logistic regression analyses were used to examine MGUS prevalence for age by gender, race/ethnicity groups, and geographic region.14,15 Age-adjusted prevalence rates, directly standardizing to the U.S. age distribution in 2000, were compared to similarly adjusted rates reported in the predominantly white Olmsted County study.11 Risk factors for MGUS were studied using available survey information (including medical exams, routine blood tests, questionnaires concerning medical history, nutrition, and demographics) available from NHANES. We first conducted risk factor analyses involving a pre-defined set of variables that, based on prior studies, have been suggested as having potential associations with MGUS, namely body mass index (BMI),16–18 socioeconomic status (SES),16,19 immunostimulatory factors,17–21 smoking, vitamin D,20,21 and pesticide exposure.22,23 We explored the role of SES by using educational and poverty index ratio as proxy markers. Subsequently, we performed exploratory analyses looking for new risk factors associated with MGUS and with racial disparity. All analyses were conducted using SAS version 9.2 (SAS Institute Inc, Cary, NC) and SUDAAN version 10.0.1 (Research Triangle Institute, Research Triangle Park, NC) software programs. All analyses accounted for the sample weighting and complex sample design of the NHANES and correction for non-response. All hypothesis tests were determined significant for two-sided p-values <0.05.

RESULTS

Prevalence

Of 13,278 adults age ≥50 years enrolled in NHANES III or NHANES 1999–2004, stored serum samples to test for monoclonal proteins were available on 12,482 persons (2,331 non-Hispanic blacks considered “black”, 2,475 Mexican-Americans, 7,051 non-Hispanic whites considered “white”, and 625 “others”). MGUS confirmed on serum immunofixation was identified in 365 participants, for an overall prevalence of 2.4% (95% CI, 2.0–2.7) (Table 1). MGUS was detected in 144 of 6,413 sampled women, as compared to 221 of 6,069 men, and prevalence rates were higher (p=0.011) in men (2.8%; 95% CI, 2.4–3.3) than in women (2.0%; 95% CI, 1.6–2.5). The unweighted median age among MGUS for both sexes was 71.8 years. From fitted restricted cubic spline regression, the prevalence of MGUS increased with advancing age in both sexes; beyond 60 years of age, however, men consistently had higher prevalence rates than women (Figure 1A).

TABLE 1.

Prevalence of monoclonal gammopathy of undetermined significance (MGUS) (%), by race and gender

Variable Black % (95%CI) White % (95%CI) Mexican-American % (95%CI) Total % (95%CI) P value*
Age group, yr
50–59 2.19 (1.32–3.60) 1.01 (0.62–1.66) 0.85 (0.33–2.23) 1.20 (0.83–1.72) 0.16
60–69 3.48 (2.26–5.33) 2.43 (1.72–3.43) 2.41 (1.69–3.44) 2.45 (1.85–3.23) 0.24
70–79 5.67 (3.66–8.70) 3.44 (2.55–4.63) 2.51 (1.36–4.58) 3.43 (2.64–4.47) 0.022
80+ 8.56 (4.92–14.47) 4.42 (3.31–5.87) 3.97 (1.33–11.22) 4.58 (3.54–5.90) 0.15
Sex
Male 4.03 (2.97–5.45) 2.84 (2.42–3.33) 2.29 (1.47–3.55) 2.84 (2.44–3.29) 0.049
Female 3.40 (2.4–4.70) 1.91 (1.43–2.55) 1.26 (0.78–2.04) 1.98 (1.55–2.54) 0.0015
Total 3.67 (2.91–4.63) 2.33 (1.99–2.73) 1.75 (1.24–2.48) 2.37 (2.05–2.74) 0.00011

Figure 1.

Figure 1

Figure 1

Prevalence of Monoclonal Gammopathy of Undetermined Significance (MGUS) in Men and Women by Age (1A) and by race and ethnicity (1B)

Of the 365 cases of MGUS for which race or ethnic group was known, 90 participants were black (25%), 214 were white (58%), and 52 were Mexican-American (14%). The adjusted prevalence rate was significantly higher (p<0.001) in blacks (3.7%) compared with whites (2.3%) (p=0.001) or Hispanics (1.8%) (Table 1). For all races, the prevalence of MGUS increased with advancing age, but blacks displayed consistently higher prevalence rates. The spline model shown on Figure 1B suggests an earlier age of onset for blacks, as well as a relatively similar prevalence between whites and Mexican-Americans prior to age 70.

Table 2 contrasts the NHANES prevalence rates among whites with the reported prevalence from the predominantly white population of Olmsted County. 11 The weighted NHANES prevalence of MGUS in whites was significantly lower (p<0.05) compared with Olmsted County, 2.3% versus 3.2%, respectively. After directly standardizing all prevalence rates to the 2000 U.S. population, the Olmsted County rates among patients over 50 years of age (4.0% in men and 2.7% in women) were still greater than the NHANES weighted results (2.8% in men and 2.0% in women). Consequently, we further examined MGUS prevalence by region of the country in the NHANES III sample because region is not publicly available in NHANES 1999–2004. The unadjusted prevalence combining the North and Midwest regions was 3.1% (95% CI 2.2%–4.0%) versus 2.1% (95% CI 1.4%–2.7%) in the combined South and West regions. The corresponding adjusted prevalence (adjusted for age, education, sex, race, smoking using logistic regression) was 3.1% (95% CI 2.2%–4.1%) and 2.1% (95% CI 1.4%2.7%) for the North and Midwest versus South and West, respectively (p=0.052).

TABLE 2.

Prevalence (%) of monoclonal gammopathy of undetermined significance (MGUS) comparing the mostly white population of Olmsted County, Minnesota with NHANES.

Olmsted County, Minnesota NHANES
All Whites
Unadjusted Adjusted Adjusted Adjusted
Men 3.7 4.0 (3.5–4.4) 3.0 (2.4–3.3) 2.8 (2.4–3.2)
Women 2.90 2.7 (2.4–3.0) 2.0 (1.5–2.5) 1.9 (1.4–2.5)
Total 3.20 3.2 (3.0–3.5) 2.4 (2.1–2.8) 2.3 (1.9–2.7)

Risk factors

MGUS prevalence tended to be higher with increasing BMI in all ethnic/racial groups, although differences did not reach statistical significance, p=0.20. To further elucidate the underlying relationship, we looked at gradations of C-peptide, insulin, and glucose in relation to MGUS prevalence, but none were significant (Supplemental Table). We also evaluated rheumatoid arthritis in relation to MGUS prevalence in order to explore the plausible role of immune dysregulation; our results show no statistical increased prevalence of MGUS in persons with arthritis or a history of arthritis, p=0.57 (Table 3). Additional exploratory analysis to determine other associated factors such as C-reactive protein and vitamin D did not reveal any significant associations (Supplemental Table), Likewise, neither smoking nor dichlorodiphenyldichloroethylene (DDE), a major metabolite of dichlorodiphenyltrichloroethane (DDT) was associated with an increased prevalence of MGUS (Supplemental Table). A non-significant association of MGUS with higher education and lower poverty income ratio (Table 3) was observed for blacks and for Mexican-Americans but not for whites.

TABLE 3.

Adjusted prevalence* (%) of monoclonal gammopathy of undetermined significance (MGUS) across variables with a previously reported association

Variable Black % (se) White % (se) Mexican-American % (se) Total % (se) P value**
BMI group, kg/m2
 <25 3.77 (0.78) 1.96 (0.31) 1.39 (0.43) 1.99 (0.27)
 25–<30 4.15 (0.80) 2.35 (0.27) 2.24 (0.72) 2.43 (0.25)
 30+ 4.40 (0.90) 2.56 (0.33) 2.33 (0.67) 2.72 (0.32) 0.20
Rheumatoid arthritis
 Yes 3.43 (0.67) 2.39 (0.32) 2.00 (0.63) 2.50 (0.31)
 No 4.68 (0.75) 2.22 (0.25) 2.05 (0.43) 2.28(0.23) 0.57
Education
 <High school 3.67 (0.51) 2.20 (0.28) 1.78 (0.35) 2.17 (0.22)
 >=High school 4.44 (0.87) 2.34 (0.24) 2.46 (0.82) 2.48 (0.23) 0.33
Income status
 Poverty 3.97 (0.92) 2.71 (0.68) 1.87 (0.52) 2.55 (0.48)
 No poverty 4.18 (0.63) 2.29 (0.21) 2.25 (0.50) 2.40 (0.20) 0.76
Smoking
 Never 4.63 (0.74) 2.26 (0.24) 1.54 (0.49) 2.34 (0.22)
 Former 3.37 (0.78) 2.31 (0.30) 2.46 (0.64) 2.42 (0.28)
 Current 4.06 (1.00) 2.31 (0.55) 2.37 (0.87) 2.32 (0.43) 0.97

Laboratory characteristics of MGUS

The laboratory characteristics of the MGUS detected in this study are shown in Table 4; these factors have a direct impact on the risk and type of progression. The IgM immunoglobulin isotype was less common in blacks compared with whites, 3% versus 15%, respectively, although the numbers are small. Conversely, the median monoclonal protein concentration was higher in black participants (0.83 g/dL (95% CI 0.66, 1.00) compared with whites (0.70 g/dL (95% CI 0.69, 0.79). However, the range of individual M-protein values was wider in whites (unmeasurable-3.3 g/dL) compared with blacks (unmeasurable-2.9 g/dL). IgA MGUS was more common in Mexican-Americans (Table 3).

TABLE 4.

Characteristics of the subjects with monoclonal gammopathy of undetermined significance (MGUS), by race/ethnicity

Total, n Black White Mexican-American
90 214 51
Male sex % (n) 46.9 (51) 55.4(133) 62.3 (33)
Age, categories, % (n)
 50–59 26.1 (17) 16.6 (18) 23.8 (6)
 60–69 29.2 (30) 30.4 (45) 43.7 (25)
 70–79 28.3 (29) 32.5 (72) 20.6 (14)
 80+ 16.4 (14) 20.5 (79) 11.9 (6)
Immunoglobulin isotype, % (n)
 IgG 76.1 (71) 68.1 (150) 63.1 (29)
 IgA 5.2 (5) 9.7 (12) 16.7 (8)
 IgM 2.7 (3) 15.4 (34) 7.4 (6)
 Biclonal 15.9 (11) 6.8 (18) 12.8 (8)
Light Chain type, % (n)
 Kappa 53.7 (48) 56.2 (120) 50.4 (27)
 Lambda 30.4 (31) 37.0 (76) 36.8 (16)
 Biclonal 15.4 (11) 6.8 (18) 12.8 (8)
Monoclonal protein, g/dl
 Median (95% CI) 0.83 (0.66–1.00) 0.70 (0.69–0.79) 0.73 (0.54–0.95)
 Range Unmeasurable-2.90 Unmeasurable-3.28 Unmeasuable-3.20

DISCUSSION

MM is significantly more common in blacks,8 possibly related to a higher prevalence of MGUS, the precursor premalignant stage of MM, in blacks. However, data on the prevalence of MGUS in populations with substantial racial diversity is sparse and irresolute.9,10 In the present study, which represents the first and largest screening study of MGUS with available risk-factor data, we were able to include approximately 12,400 adults ≥50 years old to accurately quantify the prevalence of MGUS by race and ethnicity in a stratified random sampling of the entire U.S. We demonstrate that the prevalence of MGUS is indeed significantly higher in blacks compared with whites. Moreover, this study estimates the prevalence of MGUS in Mexican-Americans for the first time; our results show prevalence rates in Mexican-Americans that are slightly lower, but overall, relatively similar to whites.

Not only did blacks have a higher overall prevalence of MGUS, but the excess continued to increase with advancing age. This rendered the elderly black population above 80 years of age with a prevalence of 8.6%, a rate nearly double that of whites of the same age. Across all age-groups, the prevalence of MGUS in blacks was similar to that seen in whites and Mexican-Americans a decade older. These results suggest racial heterogeneity early in the carcinogenic disease pathway, while also consistent with the younger age distribution seen among blacks compared with whites in MM.

In addition to a higher prevalence, MGUS in the black population was also more likely to have features associated with a greater risk of progression to MM or related disorder.6 Thus, compared to whites, blacks and Mexican-Americans had a strikingly lower rate of IgM MGUS, which progresses primarily to Waldenström’s macroglobulinemia (WM), and rarely transforms to MM. These results are consistent with other studies showing lower rates of IgM MGUS in blacks and are in accordance with the racial composition of WM.24 Contrary to prior investigations,24 blacks also had higher M protein levels, a known risk factor for progression to MM, compared with whites and Hispanics. The result is that blacks not only are more likely to have MGUS, but are also probably also at greater risk of progression with M proteins that are larger and with greater racial disparity in the non IgG type. Molecular analyses are warranted in order to further elucidate the disparity of cytogenetic subtypes among the races, and to evaluate possible differences in prognosis and progression within racial and ethnic groups. Moreover, this disparity may affect counseling efforts.

Our previous studies suggest that racial disparities in MGUS may be related more to genetic rather than environmental differences. For example, we showed that the increased prevalence of MGUS in African-Americans is also seen in blacks from Ghana, Africa.25 Moreover, when women of similar SES were studied, the prevalence of MGUS was twice as high in African-Americans compared with whites.16 Since the increased prevalence of MGUS in blacks appeared to be independent of other confounding factors, including markers for health and disease status such as smoking and SES, environmental factors are less likely to account for these effects.

Another major finding of our study is that the prevalence of MGUS in whites across the U.S. is significantly lower than the rates previously reported for Olmsted County, where 694 of the 21,463 enumerated residents (99% white) had MGUS. Comparably age- and sex-adjusted, the prevalence of MGUS in the current study was 2.4% overall (2.3% in whites) versus the prevalence of 3.2% reported in Olmsted County residents.11 However, we get closer agreement with Olmsted County for the prevalence of MGUS as estimated from the combined North and Midwest regions of NHANES III, where the prevalence was 3.1% but drops to 2.1% for the South and West regions from the NHANES III. Furthermore, the death rate from MM is much higher in Minnesota than in most other regions of the country.26 Because MM is a highly fatal disease, these deaths are probably a reasonable indicator of MM incidence; and, because MM is almost always preceded by MGUS, this suggests that the regional discrepancies in MGUS prevalence that we have observed are real. The underlying causes of these striking geographical variations in the prevalence of MGUS among U.S. whites need to be investigated in future studies since they may provide etiologic clues based on environmental exposures and ethnic differences in North and Midwest populations compared to the South and West regions of the U.S.

Uniquely, we were also able to analyze data from the NHANES survey research program in order to investigate the association of MGUS with numerous potential risk factors. Male gender and advancing age were independently associated with a higher prevalence of MGUS, consistent with previous studies.24 The finding of increased prevalence with age has implications for screening, follow-up and attribution of associations in elderly patients. On further analysis, there was a trend to higher risk of MGUS with increasing BMI (Table 3). Smaller studies16–18,27 have associated obesity with an excess risk of MGUS and MM, and the present study provides supporting evidence for this association.16–18,27 However, our attempt to explain this association by assessing mechanistic associations with factors such as C-peptide, insulin, or glucose levels did not reveal additional correlations. Our data provides some support to prior studies that have suggested an association between low SES and MGUS.16,19 Previous registry-based studies have also suggested immune-mediated conditions, such as rheumatoid arthritis, as possible correlates of MGUS and MM,28–30 but we were unable to confirm this.

In this comprehensive screening study, we provide the basis for the increased risk of MM in blacks, by demonstrating an unequivocal increase in the prevalence of the precursor lesion MGUS, and by showing that the type of MGUS in blacks carries a higher risk of progression. We also find a strong geographic disparity in the prevalence of MGUS between the North/Midwest versus the South/West regions of the U.S., a finding that has etiologic implications. Advancing age, male sex, increasing BMI, and low SES were associated with a trend to increased risk of MGUS across all racial/ethnic groups. These findings have implications for prognosis, counseling, and public health policy. Our study design utilizing the NHANES allows for our results and conclusions to be wholly representative of the U.S. population.

Supplementary Material

Supplemental Table 1

Acknowledgments

This work was supported in part by National Cancer Institute grants CA168762, CA 107476, CA 62242, CA 100707, CA 83724; the Intramural Program of the National Cancer Institute; the Jabbs Foundation (Birmingham, United Kingdom); and the Henry J. Predolin Foundation, USA.

Footnotes

Author Contribution Statement:

O.L., B.I.G., and S.V.R. designed the research, analyzed the data, wrote and edited the manuscript. J.A.K., R.A.K., I.A., R.C., S.K.K., A.D., A.J.G., T.M.T., L.J.M., N.E., N.K., M.R., R.C., and G.M.M., participated in data interpretation, reviewed the manuscript, and provided comments. All authors reviewed and approved the final manuscript.

Conflict-of-interest disclosure: The authors declare no competing financial interest.

References

  • 1.Kyle RA, Rajkumar SV. Multiple Myeloma. N Engl J Med. 2004;351:1860–1873. doi: 10.1056/NEJMra041875. [DOI] [PubMed] [Google Scholar]
  • 2.Landgren O, Kyle RA, Pfeiffer RM, et al. Monoclonal gammopathy of undetermined significance (MGUS) consistently precedes multiple myeloma: a prospective study. Blood. 2009 Jan 29;113(22):5412–5417. doi: 10.1182/blood-2008-12-194241. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 3.Weiss BM, Abadie J, Verma P, Howard RS, Kuehl WM. A monoclonal gammopathy precedes multiple myeloma in most patients. Blood. 2009 May 28;113(22):5418–5422. doi: 10.1182/blood-2008-12-195008. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 4.Kyle RA, Rajkumar SV. Criteria for diagnosis, staging, risk stratification and response assessment of multiple myeloma. Leukemia. 2009;23:3–9. doi: 10.1038/leu.2008.291. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 5.Kyle RA, Therneau TM, Rajkumar SV, et al. A long-term study of prognosis of monoclonal gammopathy of undetermined significance. N Engl J Med. 2002;346:564–569. doi: 10.1056/NEJMoa01133202. [DOI] [PubMed] [Google Scholar]
  • 6.Rajkumar SV, Kyle RA, Therneau TM, et al. Serum free light chain ratio is an independent risk factor for progression in monoclonal gammopathy of undetermined significance (MGUS) Blood. 2005;106:812–817. doi: 10.1182/blood-2005-03-1038. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 7.Greenberg AJ, Vachon CM, Rajkumar SV. Disparities in the prevalence, pathogenesis and progression of monoclonal gammopathy of undetermined significance and multiple myeloma between blacks and whites. Leukemia. 2012;26(4):609–614. doi: 10.1038/leu.2011.368. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 8.Waxman AJ, Mink PJ, Devesa SS, et al. Racial disparities in incidence and outcome in multiple myeloma: a population-based study. Blood. 2010 Dec 16;116(25):5501–5506. doi: 10.1182/blood-2010-07-298760. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 9.Cohen HJ, Crawford J, Rao MK, Pieper CF, Currie MS. Racial differences in the prevalence of monoclonal gammopathy in a community-based sample of the elderly.[erratum appears in Am J Med 1998 Oct;105(4):362] Am J Med. 1998;104(5):439–444. doi: 10.1016/s0002-9343(98)00080-1. [DOI] [PubMed] [Google Scholar]
  • 10.Landgren O, Gridley G, Turesson I, et al. Risk of monoclonal gammopathy of undetermined significance (MGUS) and subsequent multiple myeloma among African American and white veterans in the United States. Blood. 2006 Feb 1;107(3):904–906. doi: 10.1182/blood-2005-08-3449. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 11.Kyle RA, Therneau TM, Rajkumar SV, et al. Prevalence of Monoclonal Gammopathy of Undetermined Significance. N Engl J Med. 2006 Mar 30;354(13):1362–1369. doi: 10.1056/NEJMoa054494. [DOI] [PubMed] [Google Scholar]
  • 12.Ezzati TM, Massey JT, Waksberg J, Chu A, Maurer KR. Sample design: Third National Health and Nutrition Examination Survey. Vital Health Stat. 1992 Sep;2(113):1–35. [PubMed] [Google Scholar]
  • 13.Curtin LR, Mohadjer LK, Dohrmann SM, et al. The National Health and Nutrition Examination Survey: Sample Design, 1999–2006. Vital Health Stat. 2012 May;2(155):1–39. [PubMed] [Google Scholar]
  • 14.Korn EL, Graubard BI. Analysis of Health Survey. New York, NY: Wiley; 1999. [Google Scholar]
  • 15.Durrleman S, Simon R. Flexible regression models with cubic splines. Statistics in medicine. 1989 May;8(5):551–561. doi: 10.1002/sim.4780080504. [DOI] [PubMed] [Google Scholar]
  • 16.Landgren O, Rajkumar SV, Pfeiffer RM, et al. Obesity is associated with an increased risk of monoclonal gammopathy of undetermined significance (MGUS) among African-American and Caucasian women. Blood. 2010 Apr 26;116(7):1056–1059. doi: 10.1182/blood-2010-01-262394. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 17.Blair CK, Cerhan JR, Folsom AR, Ross JA. Anthropometric characteristics and risk of multiple myeloma. Epidemiology. 2005 Sep;16(5):691–694. doi: 10.1097/01.ede.0000172135.61188.2d. [DOI] [PubMed] [Google Scholar]
  • 18.Britton JA, Khan AE, Rohrmann S, et al. Anthropometric characteristics and non-Hodgkin’s lymphoma and multiple myeloma risk in the European Prospective Investigation into Cancer and Nutrition (EPIC) Haematologica. 2008 Nov;93(11):1666–1677. doi: 10.3324/haematol.13078. [DOI] [PubMed] [Google Scholar]
  • 19.Baris D, Brown LM, Silverman DT, et al. Socioeconomic status and multiple myeloma among US blacks and whites. Am J Public Health. 2000 Aug;90(8):1277–1281. doi: 10.2105/ajph.90.8.1277. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 20.Landgren O. Sun, mother of life, prevents cancer. Blood. 2011 Aug 11;118(6):1431–1432. doi: 10.1182/blood-2011-06-359794. [DOI] [PubMed] [Google Scholar]
  • 21.Chang ET, Canchola AJ, Cockburn M, et al. Adulthood residential ultraviolet radiation, sun sensitivity, dietary vitamin D, and risk of lymphoid malignancies in the California Teachers Study. Blood. 2011 Aug 11;118(6):1591–1599. doi: 10.1182/blood-2011-02-336065. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 22.Landgren O, Kyle RA, Hoppin JA, et al. Pesticide exposure and risk of monoclonal gammopathy of undetermined significance (MGUS) in the Agricultural Health Study. Blood. 2009 Apr 22;25(113):6386–6391. doi: 10.1182/blood-2009-02-203471. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 23.Alavanja MC, Sandler DP, Lynch CF, et al. Cancer incidence in the agricultural health study. Scand J Work Environ Health. 2005;31 (Suppl 1):39–45. discussion 35–37. [PubMed] [Google Scholar]
  • 24.Landgren O, Weiss BM. Patterns of monoclonal gammopathy of undetermined significance and multiple myeloma in various ethnic/racial groups: support for genetic factors in pathogenesis. Leukemia. 2009 Oct;23(10):1691–1697. doi: 10.1038/leu.2009.134. [DOI] [PubMed] [Google Scholar]
  • 25.Landgren O, Katzmann JA, Hsing AW, et al. Prevalence of Monoclonal Gammopathy of Undetermined Significance Among Men in Ghana. Mayo Clin Proc. 2007 Dec 1;82(12):1468–1473. doi: 10.1016/S0025-6196(11)61089-6. [DOI] [PubMed] [Google Scholar]
  • 26.Ries LAG, Melbert D, Krapcho M, et al. SEER Cancer Statistics Review, 1975–2005, based on November 2007 SEER data submission. Bethesda, MD: National Cancer Institute; 2008. [Google Scholar]
  • 27.Renehan AG, Tyson M, Egger M, Heller RF, Zwahlen M. Body-mass index and incidence of cancer: a systematic review and meta-analysis of prospective observational studies. Lancet. 2008 Feb 16;371(9612):569–578. doi: 10.1016/S0140-6736(08)60269-X. [DOI] [PubMed] [Google Scholar]
  • 28.Kristinsson SY, Goldin LR, Bjorkholm M, Koshiol J, Turesson I, Landgren O. Genetic and immune-related factors in the pathogenesis of lymphoproliferative and plasma cell malignancies. Haematologica. 2009 Nov;94(11):1581–1589. doi: 10.3324/haematol.2009.008979. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 29.Brown LM, Gridley G, Check D, Landgren O. Risk of multiple myeloma and monoclonal gammopathy of undetermined significance among white and black male United States veterans with prior autoimmune, infectious, inflammatory, and allergic disorders. Blood. 2008 Apr 1;111(7):3388–3394. doi: 10.1182/blood-2007-10-121285. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 30.Hakulinen T, Isomaki H, Knekt P. Rheumatoid arthritis and cancer studies based on linking nationwide registries in Finland. The American journal of medicine. 1985 Jan 21;78(1A):29–32. doi: 10.1016/0002-9343(85)90242-6. [DOI] [PubMed] [Google Scholar]

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Supplemental Table 1