Medical History, Lifestyle, Family History, and Occupational Risk Factors for Lymphoplasmacytic Lymphoma/Waldenstrom's Macroglobulinemia: The InterLymph Non-Hodgkin Lymphoma Subtypes Project

Abstract

This pooled analysis confirmed associations with immune conditions and family history of hematologic malignancy, and identified new associations with hay fever, weight, smoking, and occupation, and no association with other lifestyle factors. These findings offer clues to LPL/WM biology and prevention.

Rationale and Design of the International Lymphoma Epidemiology Consortium (InterLymph) Non-Hodgkin Lymphoma Subtypes Project

“…Findings from this project, as described in subsequent articles in this issue (78)(79)(80)(81)(82)(83)(84)(85)(86)(87)(88)(89), accomplish two of the primary goals of the consortium: investigation of the etiology of specific NHL subtypes and comparison of risk factors, including those of rare prevalence, among NHL • Data were collected and analyzed separately by beverage type (e.g., beer, wine, and liquor) and then summed to evaluate total alcohol consumption (15 studies), or collected only for any alcohol consumption (two studies).…”

“…The InterLymph NHL Subtypes Project demonstrates the benefits of long-term and large-scale international collaboration for advancing etiologic research. Results from the project identify important associations with specific NHL subtypes for some risk factors and shared among multiple NHL subtypes for others (78)(79)(80)(81)(82)(83)(84)(85)(86)(87)(88)(89). Findings also suggest possible mechanisms of lymphomagenesis and provide clues for prevention with modifiable risk factors.…”

Waldenström macroglobulinemia: What a hematologist needs to know

“…Although a recent pooled data analysis confirmed the increased risk of hematologic malignancies in ≥1 first degree relatives, the analysis highlighted a moderately increased risk for a family history of leukemias, and surprisingly, not for lymphomas or MM [13]. Familial cases are typically diagnosed a decade earlier than cases arising sporadically [14].…”

“…Over 90% of patients with greater than 50% of marrow involvement at diagnosis progress to symptomatic WM in the first 5 years compared to one-half of those with an infiltration of ≤50% [45]. Overall survival of patients with smoldering WM is found to be similar to that of the general population of comparable age and sex [13]. Although most patients eventually receive treatment, approximately 10% of those who are managed expectantly will not require therapy for over 10 years [44].…”

Familial predisposition and genetic risk factors for lymphoma

“…In contrast, there was strong evidence for heterogeneity for a family history of leukemia (P Homogeneity 5 3.9 3 10 25 ), with family history of leukemia most strongly associated with risk of CLL, LPL/WM, MCL, and PTCL. Of note, the associations for family history of NHL with risk of NHL 12 or specific NHL subtypes (eg, DLBCL, 16 FL, 17 CLL, 18 MZL, 19 LPL/WM, 20 and PTCL 21 ) remained unchanged after adjusting for extensive subtype-specific risk factors, suggesting that the association of family history may be predominately driven by shared genetics over a shared environment (Table 1). 12,[22][23][24][25][26][27] Although the International Lymphoma Epidemiology Consortium did not report pooled results for risk of HL, a large case-control study conducted in Scandinavia 26 reported an elevated risk of HL with a family history of HL (OR 5 3.3), NHL (OR 5 3.3), and CLL (OR 5 6.3).…”