Correspondence

Familial Myeloma

N Engl J Med 2008; 359:1734-1735October 16, 2008

Article

To the Editor:

Lynch et al. (July 10 issue)1 report on a family in which members had multiple myeloma or other tumors. Using the Utah Population Database, a resource including 2.5 million persons with genealogic data linked to the Utah Surveillance, Epidemiology, and End Results (SEER) cancer registry, we investigated the aggregation of multiple myeloma and coaggregation of multiple myeloma with other cancers. Aggregation beyond first-degree relatives is particularly interesting as a way of separating the role of genetics from that of a shared environment. We were able to perform these more extensive familial analyses using the Utah resource through funding from the National Cancer Institute and the International Myeloma Foundation. Data from 1354 persons with multiple myeloma and their 13,288 first-degree relatives, 45,575 second-degree relatives, and 118,363 third-degree relatives showed a significant excess of cases of multiple myeloma, prostate cancer, and melanoma in all types of relatives (P=0.039 to P=1.7×10⁻⁹). There was also a significant increase in cases of prostate cancer (P=0.028) and melanoma (P=0.04) among patients with multiple myeloma. In addition, we identified 72 pedigrees with a significant excess of both multiple myeloma and prostate cancer (P<0.05). These and other observations1-4 suggest that the genetic cause of multiple myeloma overlaps with the causes of prostate cancer and melanoma.

Nicola J. Camp, Ph.D.
Theresa L. Werner, M.D.
Lisa A. Cannon-Albright, Ph.D.
University of Utah, Salt Lake City, UT 84108
nicola.camp@utah.edu

4 References

1. 1

   Lynch HT, Ferrara K, Barlogie B, et al. Familial myeloma. N Engl J Med 2008;359:152-157
   Full Text | Web of Science | Medline

2. 2

   Lynch HT, Watson P, Tarantolo S, et al. Phenotypic heterogeneity in multiple myeloma families. J Clin Oncol 2005;23:685-693
   CrossRef | Web of Science | Medline

3. 3

   Eriksson M, Hallberg B. Familial occurrence of hematologic malignancies and other diseases in multiple myeloma: a case-control study. Cancer Causes Control 1992;3:63-67
   CrossRef | Web of Science | Medline

4. 4

   Dilworth D, Liu L, Stewart K, Berenson JR, Lassam N, Hogg D. Germline CDKN2A mutation implicated in predisposition to multiple myeloma. Blood 2000;95:1869-1871
   Web of Science | Medline

Author/Editor Response

A cardinal rule of the delineation of a hereditary cancer syndrome is a comprehensive family history of cancer that includes cancers at all anatomical sites. Clinical examples such as the hereditary breast–ovarian cancer syndrome and the Lynch syndrome are legion, and the list goes on.1 Albright et al.2 quantified a statistical association in a population-based study of multiple myeloma, prostate cancer, and malignant melanoma involving all types of relatives (P=0.027 to P=8.3×10⁻⁹). They identified 72 pedigrees with a significant excess of both multiple myeloma and prostate cancer. Our studies of familial multiple myeloma3 as well as others from the literature4 that attempt to define a genetic association between multiple myeloma and prostate cancer underscore the power of tumor aggregation, yet a common molecular genetic pathway explaining this putative association with hereditary cancer remains elusive.

Henry T. Lynch, M.D.
Stephan Thomé, M.D., Ph.D.
Creighton University School of Medicine, Omaha, NE 68178

4 References

1. 1

   Watson P, Vasen HFA, Mecklin J-P, et al. The risk of extra-colonic, extra-endometrial cancer in the Lynch syndrome. Int J Cancer 2008;123:444-449
   CrossRef | Web of Science | Medline

2. 2

   Albright LA, Schwab A, Camp NJ, Farnham JS, Thomas A. Population-based risk assessment for other cancers in relatives of hereditary prostate cancer (HPC) cases. Prostate 2005;64:347-355
   CrossRef | Web of Science | Medline

3. 3

   Lynch HT, Watson P, Tarantolo S, et al. Phenotypic heterogeneity in multiple myeloma families. J Clin Oncol 2005;23:685-693
   CrossRef | Web of Science | Medline

4. 4

   Eriksson M, Hallberg B. Familial occurrence of hematologic malignancies and other diseases in multiple myeloma: a case-control study. Cancer Causes Control 1992;3:63-67
   CrossRef | Web of Science | Medline

Citing Articles (3)

Citing Articles

1. 1

   Sigurdur Y. Kristinsson, Magnus Björkholm, Lynn R. Goldin, Cecilie Blimark, Ulf-Henrik Mellqvist, Anders Wahlin, Ingemar Turesson, Ola Landgren. (2009) Patterns of hematologic malignancies and solid tumors among 37,838 first-degree relatives of 13,896 patients with multiple myeloma in Sweden. International Journal of Cancer 125:9, 2147-2150
   CrossRef

2. 2

   O Landgren, B M Weiss. (2009) Patterns of monoclonal gammopathy of undetermined significance and multiple myeloma in various ethnic/racial groups: support for genetic factors in pathogenesis. Leukemia 23:10, 1691-1697
   CrossRef

3. 3

   H. T. Lynch, S. D. Thome. (2009) Familial multiple myeloma. Blood 114:4, 749-750
   CrossRef