Genetic and environmental factors driving hematologic cancer rates in Atlantic Canada

1. To evaluate environmental factors that contribute to multiple myeloma (MM) and Waldenström’s macroglobulinemia (WM) in the Atlantic Provinces using geographical correlations of metalloid environmental carcinogens by ICP-MS analysis of heavy metals.
2. To uncover germline variants that predispose to MM and WM and compare the somatic mutational profile of those with versus without deleterious germline variants using whole-genome sequencing.
3. To compare the genetic mutational profiles with RNA expression in these cancers from individuals with and without identified predisposition variants as well as those with high vs low levels of environmental risk factor exposure. 

Multiple myeloma (MM) and Waldenström’s macroglobulinemia (WM) are chronic cancers of the blood and bone marrow system for which there currently is no cure. These cancers can result in severe chronic pain, fractures, kidney failure, stroke, visual loss, bleeding, and premature death. In the Atlantic Provinces, we observe a high number of cases of MM and WM, and in particular, a strikingly large proportion of these cases have been found to cluster within families. We seek to uncover the root cause(s) for the high number of cases of MM and WM, including their clustering in families, in Atlantic Canada through a detailed examination of genetic and environmental risk factors. We will use tissue samples including bone marrow and skin cells to preform genetic testing looking for changes in these individuals’ inherited DNA that made them more likely to develop these cancers than the average population. We will use bone marrow along with toenail clippings collected from these same individuals to determine their exposure to potentially cancer-causing heavy metals. We will compare these levels to those found in toenail clippings from healthy, cancer-free, individuals participating in the Atlantic Partnership for Tomorrow’s Health (Atlantic PATH) project. Findings from this research will provide valuable information on the absolute and relative contribution of both inherited genetic and environmental risk factors present in Atlantic Canada that predispose to MM and/or WM. The identification of these factors will have immediate as well as future impacts, enabling targeted screening and early detection for potentially at- risk family members as well as guidance for risk factor reduction strategies. Results will be translated back into the clinical setting through incorporation of newly identified predisposing genes into locally available clinical genetic testing.