Abstract 5882: Birth characteristics and risk of early-onset myeloproliferative neoplasms in a population-based case-control study

Abstract

Abstract Background: Philadelphia chromosome negative myeloproliferative neoplasms (MPN) have driver mutations that are acquired early in life, but median age at diagnosis for MPN is 65-69 years and they are infrequent among children, adolescents, and young adults. No epidemiological studies have examined the risk factors for early-onset MPN (EO-MPN), likely due to its rarity, and the etiology remains unclear. Methods: We evaluated associations between birth characteristics and EO-MPN risk in a population-based case-control study nested within a California birth cohort. The study included 219 cases of MPN (75 with polycythemia vera [PV], 114 with essential thrombocythemia [ET], and 30 with primary myelofibrosis) diagnosed at the age of 0-37 years in California during 1988-2015, as well as 10,950 controls randomly selected from the statewide birth cohort and frequency-matched on year of birth. Data on birth characteristics including gestational age, sex, birthweight, birth order, pregnancy complications (e.g., eclampsia, toxemia, diabetes), mode of delivery, and parental ages were retrieved from birth records maintained by the California Department of Public Health. Odds ratios (OR) and 95% confidence intervals (CI) were estimated from an unconditional multivariable logistic regression model that included year of birth and birth characteristics. Results: A higher birthweight was associated with a significantly lower risk of EO-MPN (age at diagnosis: 0-37 years), and the OR for the birthweight z-score was 0.87 (95% CI: 0.78-0.98). Individuals whose mothers experienced complications during pregnancy had a higher EO-MPN risk (OR=1.54, 95% CI: 1.08-2.19). Compared to individuals born to mothers at the age of 25-29 years, those born to mothers ≥35 years had a significantly increased risk of EO-MPN (OR=1.64, 95% CI: 1.09-2.47). Stratified analyses by MPN subtype identified male sex and pre-term birth as risk factors for PV, and lower birthweight, complications during pregnancy, and older paternal age as risk factors for ET. Associations between birth characteristics and risk of EO-MPN also exhibited variations based on age of diagnosis, with lower birthweight being a risk factor for those diagnosed at 0-19 years (n=71 cases) and pregnancy complications being a risk factor for those diagnosed at 20-37 years (n=148 cases). Conclusion: In this first-ever population-based study that examined EO-MPN, our findings support a role of birth characteristics in the etiology of this rare phenotype and underscore etiological heterogeneity by MPN subtype and age of diagnosis. Citation Format: Nikolai A. Podoltsev, Rong Wang, Joseph L. Wiemels, Libby M. Morimoto, Catherine Metayer, Xiaomei Ma. Birth characteristics and risk of early-onset myeloproliferative neoplasms in a population-based case-control study [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 5882.