Abstract 1299: Effect of family history of cancer on the risk of multiple myeloma: Differences by ancestry and age of onset

Background. Multiple myeloma (MM) is the most common hematologic malignancy affecting African Americans, with a younger age of onset and standardized incidence and mortality rates that are twofold higher compared to European Americans despite the presence of clinical features, which are consistent with milder clinical course. The basis for this paradox remains poorly understood. However, evidence suggests a shared genetic susceptibility. Methods. Using 720 participants (259 confirmed MM cases; 461 age-, sex-, ancestry-matched controls) enrolled in the Molecular and Genetic Epidemiology (iMAGE) study of myeloma, we examined the risk of MM associated with a positive family history of cancer and the excess risk observed among AA patients. Family history of cancer was obtained from structured interviews and risk estimates were calculated using odds ratios (OR) and corresponding 95% confidence intervals (CI) from logistic regression stratified by ancestry and median age of MM onset (65 years). Results. Of the total participants included (42% African American), the majority reported a positive family history of cancer (80%), including solid tumors (75%), hematologic malignancies (17%) and MM (4%). A positive family history of any cancer in any relative was strongly associated with an increased risk of MM overall (OR=1.73, 95% CI 1.14-2.60; P=0.008), as well as among African Americans (P=0.03) and participants less than 65 years of age (P=0.0005). MM risk was markedly increased for participants who reported any relative with MM overall (OR=3.06, 95% CI 1.42-6.58; P=0.004) and among participants less than 65 years of age (OR=4.06, 95% CI 1.44-11.5; P=0.005). The magnitude of this effect was greater in African Americans (OR=18.6, 95% CI 2.32-148; P=0.0002) compared to European Americans, and was notable among first-degree relatives (OR=9.90, 95% CI 1.14-85.9; P=0.01). In contrast, MM risk was not significantly elevated for participants who reported relatives with any hematologic malignancy other than MM (OR=1.47, 95% CI 0.96-2.27; p=0.08) nor a positive family history of solid tumors (OR=1.36, 95% CI 0.95-1.95; P=0.09), and these estimates did not differ by ancestry, age of onset or degree of relative. Conclusions. Our observations suggest that the excess risk of MM observed among African Americans and among those with early age of onset may be attributed to shared susceptibility including underlying heritable genetic and environmental factors. Future studies are warranted to examine the relationship between family history of MM with clinical and cytogenetic factors, which are known to differ by ancestry. Citation Format: Gwendolyn I. Pruitt, Howard W. Weiner, Racquel D. Innis-Shelton, Donna Salzman, Kelly N. Godby, Vishnu B. Reddy, Fady M. Mikhail, Andrew J. Carroll, Elizabeth E. Brown. Effect of family history of cancer on the risk of multiple myeloma: Differences by ancestry and age of onset. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 1299. doi:10.1158/1538-7445.AM2014-1299