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Common Chromosomal Abnormalities Occur Less Often In African-American Than White Multiple Myeloma Patients

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Published: Mar 10, 2015 9:24 am

The results of a recently published study show that, among newly diag­nosed myeloma patients, African-Americans are less likely than white Americans to have the four most common myeloma-related chro­mo­somal ab­nor­mal­ities.

The authors of the study investigated how often the chro­mo­somal ab­nor­mal­ities t(11;14), t(4;14), del(13q), and del(17p) were present in two dif­fer­ent groups of newly diagnosed myeloma patients. One group con­sisted of African-Americans, the other of white Americans.

Each of the four ab­nor­mal­ities occurred less frequently in the African-American patients.

In addition, almost two-thirds of the African-American patients (63 per­cent) did not have any of the four ab­nor­mal­ities, compared to a third of the white patients (35 per­cent).

These findings may help explain why, in several studies, African-American myeloma patients have been found to live longer after diagnosis than white myeloma patients.

The new study included patients from four different U.S. myeloma treatment centers. The African-American group of patients numbered almost 300, and there were over 470 patients in the white group. The size of both groups of patients means that the study’s results are likely to be viewed as robust.

The study was not, however, national or international in scope, and the study authors also recognize that there may have been differences among the four treatment centers in how patients were determined to have each of the four chro­mo­somal ab­nor­mal­ities included in the study.

In addition, the study did not directly investigate how often chro­mo­somal ab­nor­mal­ities known as trisomies occurred in either of the two groups of patients. As explained later in this article, differences in how often trisomies occur in black and white myeloma patients may be the key to understanding why black myeloma patients tend to live longer after diagnosis than white myeloma patients.

Background

Multiple myeloma is known to occur much more frequently in African-Americans than in white Americans. Studies indicate that African-Americans are two to three times more likely to develop multiple myeloma than whites.  Across all types of cancer, this is one of the largest differences in how often a cancer occurs in black and white Americans.

The higher incidence of multiple myeloma in African-Americans is thought to be due to differences in how often the myeloma precursor disease, monoclonal gammopathy of undetermined significance (MGUS), occurs in blacks and whites.  MGUS is more likely to occur in black Americans than in white Americans.

In addition, a study has shown that MGUS occurs more frequently in black men in the West African country of Ghana than in white American men. This suggests that genetics, not just environmental or socioeconomic factors, play an important role in how often myeloma develops in black and white Americans.

Although African-Americans are more likely than whites to develop multiple myeloma, this does not mean myeloma is more aggressive in blacks once it is diagnosed. In fact, studies suggest just the opposite. African-Americans diagnosed with myeloma tend to live longer than whites diagnosed with the disease, even after adjusting for factors such as age and disease stage at diagnosis.

To understand better the differences in multiple myeloma between blacks and whites, an earlier study looked at how often chro­mo­some 14 translocations occur in black and white myeloma patients. This previous study found that chro­mo­some 14 translocations, also known as IgH translocations, were less frequent in African-Americans than in whites (see related Beacon news).

In the current study, researchers focused their attention on the four most common chro­mo­somal ab­nor­mal­ities found in the myeloma cells of newly diagnosed myeloma patients: t(11;14), t(4;14), del(13q), and del(17p). The researchers’ goal was to determine whether these ab­nor­mal­ities occur more or less frequently depending on a myeloma patient’s race.

Study Design

The authors of the new study compiled data for 292 African-American myeloma patients from four U.S. treatment centers: the University of Maryland at Baltimore; Cook County Hospital in Chicago; Rush University Medical Center in Chicago; and the Mayo Clinic in Rochester, Minnesota. The first three of these centers serve large African-American populations.

The researchers also constructed a comparison group of 471 white myeloma patients from the Mayo Clinic.

Patients had to be newly diagnosed with multiple myeloma between January 2006 and January 2013 to be included in the analysis.

Information on chro­mo­somal ab­nor­mal­ities was retrieved from fluorescent in situ hybridization (FISH) studies that were conducted as part of each patient’s routine clinical care. The FISH studies had to be carried out at least one year before, but not longer than six months after, a patient’s multiple myeloma diagnosis.

Patients whose FISH results indicated either monosomy 13 or del(13q) were grouped together as del(13q) for the analysis.  (A patient with monosomy 13 has myeloma cells that have only one copy of chro­mo­some 13, instead of the usual two copies.)

Similarly, patients who had either monosomy 17 or del(17p) were grouped together as del(17p).

The median age at diagnosis was 59 years for the African-American patients and 63 years for the white patients.

The share of male patients was lower in the African-American group (45 per­cent) than in the white group (60 per­cent).

Study Results

The study authors found that all four chro­mo­somal ab­nor­mal­ities occurred significantly less frequently in African-American myeloma patients than in white patients.

Specifically, 7 per­cent of the black patients had the chro­mo­somal ab­nor­mal­ity t(11;14), compared to 18 per­cent of the white patients. The t(4;14) ab­nor­mal­ity was found in 6 per­cent of African-Americans, compared to 10 per­cent in the white group.

Similarly, del(13q) occurred in 29 per­cent of the African-American patients and 47 per­cent of the white patients.  And del(17p) was found in 8 per­cent of the black patients and 13 per­cent of the white patients.

The researchers also found that significantly more African-American patients than white patients did not have any of the four ab­nor­mal­ities (63 per­cent versus 35 per­cent, respectively).

Age did not affect the key findings of the study. To show this, the researchers split patients in the study into two groups: one group included all patients under the age of 60, and the other included patients 60 years of age or older.  For each of the four chro­mo­somal ab­nor­mal­ities, African-Americans in both age groups were less likely than their white counterparts to have the ab­nor­mal­ity.

Explaining Longer Survival In African-American Myeloma Patients

The authors of the study believe that their findings help explain why African-American myeloma patients tend to live longer after diagnosis than white myeloma patients.

Almost all patients with multiple myeloma, the authors note, have one or both of two categories of chro­mo­somal ab­nor­mal­ities. The first category includes IgH translocations – that is, translocations of chro­mo­some 14. The second category includes trisomies of odd-numbered chro­mo­somes. A trisomy occurs when there are three copies of a specific chro­mo­some, instead of the usual two.

While some IgH translocations are associated with a poorer prognosis in myeloma patients, trisomies are almost always associated with a better prognosis.

The results of the current study confirm, in part, the results of the study mentioned earlier, which found that African-American myeloma patients are less likely to have IgH translocations than white myeloma patients.

Given that myeloma patients usually have either IgH translocations, trisomies, or both, the current study’s findings add to the evidence that black myeloma patients are more likely than white myeloma patients to have trisomies.

This, the authors believe, is the most likely reason why black myeloma patients tend to survive longer than white myeloma patients. Black myeloma patients, they believe, are more likely than white patients to have trisomies at the time of diagnosis, and trisomies tend to improve a myeloma patient's prognosis.

Future research will need to confirm this hypothesis, however, as neither the current study – nor the study mentioned earlier – directly measured how often trisomies occur in black and white newly diagnosed multiple myeloma patients.

For more information about the current study, please see Greenberg, A. J. et al, " Racial differences in primary cytogenetic ab­nor­mal­ities in multiple myeloma: a multi-center study," in Blood Cancer Journal, January 2, 2015 (full text of article).

Photo by victoriapeckham on Flickr – some rights reserved.
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7 Comments »

  • Eric said:

    Any explanation / hypothesis as to why?

  • Boris Simkovich said:

    Eric - The authors don't really address your question in their paper. I suspect, however, that they would say that there are genetic differences between whites and blacks that accounts for the difference.

    There is research, for example, that indicates that a heritable risk factor for MGUS and multiple myeloma is more prevalent in blacks than in whites. This paper has more on that finding:

    C Zwick et al, "Over one-third of African-American MGUS and multiple myeloma patients are carriers of hyperphosphorylated paratarg-7, an autosomal dominantly inherited risk factor for MGUS/MM," International Journal of Cancer, 2014 (abstract).

  • Kira said:

    Hello Mr. Simkovich,

    My mother passed from MM and since then I asked several times if MM is inherited. The answer that I got from many doctors and medical advisors that majority of cases are sporadic and there is no genetic testing is available for now. I did pay attention that some relatives report about them being diagnosed with MM and/or MGUS. So, my opinion that like in any other cancers there is inherited and sporadic forms.

    My question: If pP-7 inherited in autosomal dominantly pattern, is there test available for the relatives?

    Thank you in advance,
    Kira

  • Boris Simkovich said:

    Hello Kira,

    The topic of "Is myeloma something that you can inherit?" is one that comes up from time to time in the Beacon's discussion forum. There was a discussion on the topic last fall that is worth reviewing if you haven't seen it already ("Both parents had multiple myeloma - am I at risk"). As Beacon Medical Advisor Dr. Heather Landau of the Memorial Sloan-Kettering Cancer Center wrote in that discussion thread,

    "While most cases of myeloma are sporadic (meaning not driven by a familial pre­dis­po­si­tion), we do know that people who have a first degree relative (parent or sibling) with myeloma are at slightly higher risk for developing myeloma then the general population. ... BUT please know that the risk [of inheriting myeloma from a parent] is very small, as the vast MAJORITY of multiple myeloma patients have siblings, parents and children who NEVER develop the disease."

    I am not aware of any readily available test that can be conducted to test if someone has the pP-7 risk factor for developing MGUS or multiple myeloma. Since the science on this issue is relatively new, I would suspect that such testing can only be done on a custom basis.

    Thanks for your question.

  • Christel Sanders said:

    Interesting subject, Mr. Simkovich -- thanks for bringing it to us. I must have some black genes with my trisomy 11 and sometimes even as much as 8 copies of 11. Although, in the mirror, I appear as a white woman.

  • Boris Simkovich said:

    Christel - Trisomies are common in myeloma patients in general. A Mayo Clinic study found that almost 60 percent of newly diagnosed myeloma patients seen at that treatment center had at least one trisomy. So I would not assume that you have any African genes simply because of your trisomies!

    - Boris.

  • stann said:

    Eric, geneticists have found that Caucasions and Asians have a small amount of Neanderthal genes in their DNA. Whereas the humans that remained in Africa did not interact/breed with Neanderthal. I can't remember the paper, but the geneticists did suggest that the immune systems between blacks and other races had some measurable differences.