Correspondence to: Kari Hemminki, M.D., Ph.D., Department of Biosciences at Novum, Karolinska Institute, 141 57 Huddinge, Sweden (e-mail: Kari.Hemminki{at}cnt.ki.se).
Dr. Lynch and coworkers (1) described a family with several cases of multiple myeloma (MM) and other malignancies. As they pointed out, the etiology of MM remains obscure and the reviewed literature consists mainly of case reports from affected families, which do not allow a reliable estimation of familial risks for this neoplasm. Their review did not include two relevant studies: one, a cohort study (2), and the other, a casecontrol study (3) that showed a familial risk of 3.7. We would like to make three more additions to the literature on familial MM. First, the recent Nordic twin study (4) recently reported one additional monozygotic twin pair concordant for MM. The relative risk of MM for twins in this study was 22 (95% confidence interval [CI] = 2.8 to 175). The other two additions originate from the Swedish FamilyCancer Database, which has been used, in various updated versions, in some 100 family studies on diverse cancers (5). The data below were extracted from the version of the Database that included information on all the neoplasms from 9.6 million individuals recorded at the Swedish Cancer Registry between 1958 and 1996. The unique aspect of the Database is its complete national coverage of families with medically verified neoplasms.
Using this Database, we studied familial risks for all of the main cancer sites; the MM part of this study is by far the largest family study on this neoplasm (6). We calculated standardized incidence ratios (SIRs) for MM or other neoplasms among offspring 61 years old or younger whose parent presented with MM or any other cancer. The expected numbers of each cancer were derived from site-, age-, and sex-specific rates in all offspring. In Table 1 we present only the statistically significant associations between MM and other cancer sites. Familial MM showed an SIR of 4.25, which was remarkably high, in agreement with the referenced casecontrol study (3). The familial risk for MM ranked third among all neoplasms, after thyroid (SIR = 6.94) and testicular cancer (SIR = 4.31). Parental thyroid cancer was associated with MM in the offspring. Several other malignancies in offspringrectal, breast, lung, and nonthyroid endocrine cancers, as well as melanoma and lymphomawere in excess when a parent presented with MM. However, in this study, multiple comparisons may have caused chance associations. The family described by Lynch et al. (1) had a diagnosed case of melanoma, in line with our results, whereas in our study, among lymphoproliferative neoplasms, MM was associated with lymphoma but not with leukemia. Finally, we would like to refer to studies on multiple neoplasms in the same individuals because these may signal genetic susceptibility. In a recent study (7), we used the Swedish FamilyCancer Database to follow second neoplasms in more than 50 000 patients whose first diagnosis was a lymphoproliferative malignancy. When MM was the first malignancy, we observed an increased risk of non-Hodgkin's lymphoma (N = 25; SIR = 1.74; 95% CI = 1.12 to 2.57) and myeloid leukemia (N = 35; SIR = 8.19; 95% CI = 5.70 to 11.4). However, we cannot exclude the effects of treatment on this association. In summary, our family study showed one of the highest familial risks for MM among any neoplasms, suggesting heritable etiology for this malignancy. Susceptibility to MM may also increase the risk of neoplasia at other sites, but these findings need confirmation.
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REFERENCES
1
Lynch HT, Sanger WG, Pirruccello S, Quinn-Laquer B, Weisenburger DD. Familial multiple myeloma: a family study and review of the literature. J Natl Cancer Inst 2001;93:147983.
2 Grosbois B, Jego P, Attal M, Payen C, Rapp MJ, Fuzibet JG, et al. Familial multiple myeloma: report of fifteen families. Br J Haematol 1999;105:76870.[Medline]
3 Brown LM, Linet MS, Greenberg RS, Silverman DT, Hayes RB, Swanson GM, et al. Multiple myeloma and family history of cancer among blacks and whites in the U.S. Cancer 1999;85:238590.[Medline]
4
Lichtenstein P, Holm NV, Verkasalo PK, Iliadou A, Kaprio J, Koskenvuo M, et al. Environmental and heritable factors in the causation of canceranalyses of cohorts of twins from Sweden, Denmark, and Finland. N Engl J Med 2000;343:7885.
5 Hemminki K, Li X, Plna K, Granstrom C, Vaittinen P. The nation-wide Swedish Family-Cancer Database: updated structure and familial rates. Acta Oncol 2001;40:7727.[Medline]
6 Dong C, Hemminki K. Modification of cancer risks in offspring by sibling and parental cancers from 2,112,616 nuclear families. Int J Cancer 2001;92:14450.[Medline]
7 Dong C, Hemminki K. Second primary neoplasms among 53 159 haematolymphoproliferative malignancy patients in Sweden, 19581996: a search for common mechanisms. Br J Cancer 2001;85:9971005.[Medline]
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