Familial Myeloma

Lynch, Henry T.; Ferrara, Kelly; Barlogie, Bart; Coleman, Elizabeth Ann; Lynch, Jane F.; Weisenburger, Dennis D.; Sanger, Warren G.; Watson, Patrice; Nipper, Henry C.; Witt, Vinetta; Thomé, Stephan D.

doi:10.1056/nejmoa0708704

Cited by 80 publications

(67 citation statements)

References 19 publications

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“…42,43 familial cluSterinG Several small-scale reports suggest that, in some cases, familial predisposition to MGUS may be increased. 44,45 Familial aggregation of multiple myeloma, the malignant stage that follows MGUS, has been recognized for years. 46 Recently, a large population-based study in Sweden demonstrated a 2-fold increased risk of multiple myeloma among first-degree relatives of patients with multiple myeloma.…”

Section: Sexmentioning

confidence: 99%

Prevalence of Monoclonal Gammopathy of Undetermined Significance: A Systematic Review

Wadhera

Rajkumar

2010

Mayo Clinic Proceedings

138

104

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M onoclonal gammopathy of undetermined significance (MGUS) is a premalignant, asymptomatic disorder characterized by monoclonal plasma cell proliferation in bone marrow with absence of end-organ damage. 1 Although historically considered a benign condition, patients with MGUS have a lifelong risk of multiple myeloma, an incurable plasma cell malignancy with a median survival of approximately 4 to 5 years. [2][3][4] Patients with MGUS are also at risk of related disorders, such as light-chain amyloidosis and macroglobulinemia. Conditions such as osteoporosis, hip fractures, and peripheral neuropathy are also associated with MGUS. 5 The rate at which MGUS progresses to multiple myeloma or a related disorder is 1% per year. 6,7 The probability of progression at 25 years of follow-up is approximately 30%. However, after accounting for competing causes of death, true life-time probability of progression is lower (11%). 8 The risk of progression with MGUS does not diminish over time Monoclonal gammopathy of undetermined significance (MGUS) is a premalignant plasma cell disorder that is associated with a lifelong risk of multiple myeloma. We conducted a systematic review of all studies investigating the prevalence and incidence of MGUS in the online database PubMed. The review was conducted from January 6, 2009, through January 15, 2010. The following MeSH search headings were used: monoclonal gammopathy, benign and prevalence; monoclonal gammopathy, benign and incidence; paraproteinemia and prevalence; and paraproteinemia and incidence. Articles were limited to those written in English and published by January 2009. Fourteen studies that met prespecified criteria were included and systematically assessed to identify the most accurate prevalence estimates of MGUS based on age, sex, and race. On the basis of our systematic review, we estimate that the crude prevalence of MGUS in those older than 50 years is 3.2% in a predominantly white population. Studies in white and Japanese populations demonstrate a clear increase in prevalence with age. The prevalence is also affected by sex: 3.7% and 2.9% in white men and women, respectively; and 2.8% and 1.6% in Japanese men and women, respectively. Additionally, MGUS is significantly more prevalent in black people (5.9%-8.4%) than in white people (3.0%-3.6%). We conclude that MGUS is a common premalignant plasma cell disorder in the general population of those older than 50 years. The prevalence increases with age and is affected by race, sex, family history, immunosuppression, and pesticide exposure. These results are important for counseling, clinical care, and the design of clinical studies in high-risk populations. and persists even in patients whose condition has remained stable for decades. 7,9 This fixed risk of progression regardless of duration of disease suggests a random 2-hit model of progression rather than a cumulative damage accumulation model in which the risk of progression would be expected to increase with duration of MGUS. The main risk factors for progressio...

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Section: Sexmentioning

confidence: 99%

Prevalence of Monoclonal Gammopathy of Undetermined Significance: A Systematic Review

Wadhera

Rajkumar

2010

Mayo Clinic Proceedings

138

104

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“…32 To our knowledge, there have been only a few reports of familial MM in African Americans. Lynch et al 33 described an African-American family with five cases of MM, three case of MGUS and five cases of prostate cancer among 11 first-degree relatives. Jain et al 34 reported on eight African-American families with familial MM and MGUS seen in a 30-year period at a single institution.…”

Section: Yearsmentioning

confidence: 99%

“…Although this study was relatively small and there was a low response rate to the questionnaires, the results of this study are quite similar to the results of the Swedish population-based studies. Inspired by recent familial MM studies suggesting excess of certain solid tumors among blood relatives to MM patients, 33,37 we recently conducted, to our knowledge, the first populationbased study to evaluate familial aggregation patterns of 27 solid tumors and all myeloid hematological malignancies among firstdegree blood relatives of MGUS patients. 38 Compared with relatives of controls (n ¼ 58 387), first-degree relatives of MGUS patients (n ¼ 14,621) had a 10% (P ¼ 0.004) increased risk of developing solid tumors (including all tumors).…”

Section: Genetic Factors In Mgus and Myeloma O Landgren And Bm Weissmentioning

confidence: 99%

Patterns of monoclonal gammopathy of undetermined significance and multiple myeloma in various ethnic/racial groups: support for genetic factors in pathogenesis

2009

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Monoclonal gammopathy of undetermined significance (MGUS) is one of the most common premalignant disorders in Western countries. Recent studies show that almost every multiple myeloma (MM) case is preceded by an MGUS stage. Interestingly, prevalence and incidence patterns for MGUS and MM show striking disparity patterns across ethnic/racial groups, most notably the two-to threefold increase in both these disorders in African Americans compared with Caucasians. In contrast, studies on Asian patients show lower prevalence/ incidence for MGUS/MM compared with Caucasians. Familial aggregation for both MGUS and MM has been observed; the risk for MGUS or MM in family members with these disorders is increased about two-to three fold compared with the general population. Although underlying mechanisms remain unclear, there is evidence of heterogeneity among MGUS patients from different ethnic/racial groups. For example, compared with Caucasians, African-American and African MGUS patients have reportedly lower rates of immunoglobulin M (IgM) MGUS (versus IgG/IgA MGUS) and higher rates of unquantifiable immunoglobulins (Igs). This review focuses on racial disparity and familial aggregation patterns for MGUS and MM and discusses how these observations provide novel clues with regard to pathogenesis.

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“…1 These studies have a small number of patients that developed second malignancies, 49 and 59 patients, respectively. Underlying explanation for our findings, that a prior malignancy increases the risk of second malignancies in MM patients, could include genetic susceptibilities, [17][18][19][20][21][22][32][33][34][35] immunosuppression, [36][37][38] and therapy-related cancers. 12,13,39 We found MM patients with a prior cancer diagnosis to have an increased risk of developing hematological malignancy, melanoma, nonmelanoma skin cancer, and respiratory malignancy compared with MM patients who did not.…”

Section: Discussionmentioning

confidence: 99%

“…18 This might suggest that the genetic cause of MM overlaps with the causes of other cancers. [18][19][20][21][22][23] Information regarding prior malignancies and their impact on MM patients is limited. For instance, patients with prior malignancies are often excluded from clinical trials, 24,25 thus making it difficult to generalize the current literature to this group.…”

Section: Introductionmentioning

confidence: 99%

The impact of prior malignancies on second malignancies and survival in MM patients: a population-based study

et al. 2017

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Familial Myeloma

Cited by 80 publications

References 19 publications

Prevalence of Monoclonal Gammopathy of Undetermined Significance: A Systematic Review

Prevalence of Monoclonal Gammopathy of Undetermined Significance: A Systematic Review

Patterns of monoclonal gammopathy of undetermined significance and multiple myeloma in various ethnic/racial groups: support for genetic factors in pathogenesis

The impact of prior malignancies on second malignancies and survival in MM patients: a population-based study

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