The Impact of Lifestyle Factors and Occupational Exposure on Multiple Myeloma Risk in the Multiethnic Cohort Study

Introduction Multiple Myeloma (MM) is the second most common hematologic malignancy, accounting for approximately 13% of blood neoplasms and 2% of all cancers, and the most common hematologic malignancy in African Americans. Age, male sex, African American race, family history, and excess body weight are established risk factors in Whites and African Americans but have not been examined in other racial/ethnic groups. The impact of diet on MM risk is limited, and the association between occupational exposure and MM remains inconsistent. Methods We analyzed data from 91,517 men and 109,893 women aged 45 and older at enrollment in the Multiethnic Cohort Study (MEC). Cox proportional hazard regressions were used to estimate the Hazard Ratios (HRs) and 95% confidence intervals (CIs) for the association between MM risk and various factors including demographic information, body mass index (BMI), medication history, dietary habits, and occupational factors. Heterogeneity of the association between MM risk and BMI across five race/ethnicity groups was tested using the likelihood ratio test. Results Among the 201,050 participants, 942 developed MM during the follow-up period from 1998 to 2019. Within MM cases, 24.6% were non-Hispanic Whites, 33.0% were African Americans, 7.4% were Native Hawaiians, 13.8 were Japanese Americans, and 23.4% were Latinos. Females were less likely to develop MM than males (HR=0.67, 95% CI: 0.58-0.77). Compared to Non-Hispanic Whites, African Americans were at a higher risk of MM (HR=2.71, 95% CI: 2.22-3.31), as were Native Hawaiians (HR=1.57, 95% CI: 1.17-2.10) and Latinos (HR=1.32, 95% CI: 1.06-1.65). In contrast, Japanese Americans had a lower risk of MM (HR=0.59, 95% CI: 0.46-0.74). At the cohort entry, African Americans, Native Hawaiians, and Latinos were more likely to be obese or morbidly obese compared to non-Hispanic Whites (p<.001), while Japanese Americans had a lower prevalence of obesity and morbid obesity (p<.001). Compared to participants with normal weight, no statistically significant association between MM risk and being underweight or overweight was found, after adjusting for age, sex, race/ethnicity, family history, education level, smoking status, alcohol use, history of type II diabetes and asthma, and aspirin use. However, a marginal association was observed between obesity and increased MM risk (HR=1.212, 95% CI: 1.00-1.474, p=0.06), and morbid obesity was significantly associated with an increased risk of MM (HR=2.03, 95% CI: 1.38-3.00). Although the potential positive association was observed in African Americans, Native Hawaiians, and Latinos after stratifying by race/ethnicity, the estimated effect sizes did not reach statistical significance. Furthermore, there was no heterogeneity in the association between BMI and MM risk across the five race/ethnic groups (p for heterogeneity=0.23), indicating that the relationship does not differ by race/ethnic groups. Type II diabetes was associated with a reduced risk of MM (HR=0.71, 95% CI: 0.67-0.91). No significant association was observed between MM risk and any of the 11 dietary patterns analyzed, even when stratified by sex. Participants employed in chemical production or use have an elevated risk of MM (HR=1.71, 95% CI:1.09-2.67). Conclusion This study presented novel evidence of excess and decreased MM risk in Native Hawaiians and Japanese, respectively, and highlighted the importance of the metabolic and occupational risk factors for MM. The risk differences among African Americans, Native Hawaiians and Latinos corresponded to their weight differences at the cohort entry, which may help explain the race/ethnic variations in MM risk. Additionally, the inverse association between diabetes and MM risk was consistent with findings from a previous study on monoclonal gammopathy of undetermined significance (MGUS) in the MEC, an association potentially attributed due to the protective effects of Metformin.