Familial Predisposition

Reports of familial cluster of MM suggest that genetic factors may play a role in the etiology of MM. As previously discussed, neither specific genetic factors nor environmental exposures have been clearly impli-cated.140-145 From these cases and other reviews, several observations have been made. First, there is no difference between familial and non-familial MM with regard to clinical presentation, laboratory data, and prognosis. Second, the earlier age of diagnosis in successive generations is a reflection of the genetic phenomenon of anticipation.146 Third, individuals with familial MM appear to have a higher incidence of other hematologic malignancies. There is also a higher incidence of MGUS in many relatives of MM patients that puts them at a higher risk of developing MM.147 148 One report of HLA typing disclosed identical haplotypes (AW24, A26, B13, and BW55) in two sisters 58 and 56 years old, diagnosed 22 months apart.149 Other studies of familial MM in twins showed identical isotypes and in some cases similar karyotypic abnormalities.150-152 A comprehensive family cancer database from several Swedish registries included 6 million persons. There were more than 30,000 cancers reported, and an increased cancer risk in offspring (1.1 times) was noted when the father had cancer. If both parents had cancer, the risk for sons was 1.4 and for daughters 1.3. MM was among the cancers with higher risks.153 A population-based case-control interview study of 565 MM patients (361 whites and 204 blacks) and 2104 controls (1150 whites and 954 blacks) showed that family history of any cancer contributes to the risk of MM. The risk of MM was significantly elevated for patients who reported that a first-degree relative had MM (OR = 3.7, 95% CI 1.2-12.0) or any lym-phoproliferative cancer (OR = 1.7, 95% CI 1.0-2.8), especially a sibling (OR = 2.3, 95% CI 1.1-4.5). The risk associated with familial occurrence of hematologic cancer was higher for blacks than for whites. 154 However, to date the question of genetic predisposition to MM remains unanswered.155-159

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