Genetics and molecular epidemiology of multiple myeloma: The rationale for the IMMEnSE consortium (Review)

Abstract

Abstract. There is strong evidence suggesting the presence of a genetic component in the aetiology of multiple myeloma (MM). However no genetic risk factors have been unequivocally established so far. To further our understanding of the genetic determinants of MM risk, a promising strategy is to collect a large set of patients in a consortium, as successfully done for other cancers. In this article, we review the main findings in the genetic susceptibility and pharmacogenetics of MM and present the strategy of the IMMEnSE (International Multiple Myeloma rESEarch) consortium in contributing to determine the role of genetic variation in pharmacogenetics and in MM risk.

Type 2 diabetes-related variants influence the risk of developing multiple myeloma: results from the IMMEnSE consortium

“…The study population consisted of 1420 MM patients (705 women and 715 men) and 1858 controls (916 women and 942 men) ascertained through the International Multiple Myeloma (IMMEnSE) consortium (Supplementary Table 1, see section on supplementary data given at the end of this article), which has been described in detail elsewhere (Martino et al 2012). The diagnosis of MM was assigned by physician and fulfilled the International Myeloma Working Group (IMWG) criteria (International Myeloma Working Group 2003).…”

Risk of multiple myeloma is associated with polymorphisms within telomerase genes and telomere length

“…2 The IMMEnSE study population used for this study consisted of 1682 MM cases and 1894 controls recruited from seven different European countries. Briefly, cases were defined by a confirmed diagnosis of MM according to the International Myeloma Working Group (IMWG) criteria.…”

“…In Europe the incidence is slightly higher, with 4.6/ 100,000 and 3.2/100,000 new cases, respectively in men and women. Risk factors for MM have been reviewed in Martino et al 2 MM risk is clearly related to age, gender, ethnicity and the presence of pre-malignant conditions such as MGUS. There are epidemiological evidences supporting an increased risk of MM among obese people and for those who have a low intake either of fish or vegetables.…”

“…3,4 Several risk loci have been proposed and a few have been identified through genomewide association studies (GWAS). 2,[5][6][7][8][9][10][11] The genetic variability of the telomerase reverse transcriptase (TERT) and the telomerase RNA component (TERC) gene regions could play a role in MM etiology for two reasons: first the two genes are responsible for crucial cellular processes, namely telomere homeostasis, second their polymorphic variants have been found to be associated with multiple cancer types and other human phenotypes. [12][13][14][15][16][17][18][19][20][21][22][23][24] TERT and TERC constitute the telomerase complex, 25 whose correct functioning is fundamental for the accurate de novo synthesis of telomeric ends.…”

A critical review of the epidemiology of Agent Orange or 2,3,7,8-tetrachlorodibenzo-p-dioxin and lymphoid malignancies

“…Rates are higher in males than females and, in the United States, in blacks than whites, who in turn have higher rates than Asians and Pacific Islanders [28]. Besides these demographic characteristics and a family history of MM [84,85], and perhaps obesity, which appears to be associated with an approximately 20% increase in MM risk [86], virtually no risk factors for MM are well established [87e89].…”