Comparison of Chronic Health Conditions and Health Behaviors in Long-Term Young Adult Hodgkin Lymphoma (YAHL) Survivors to That of Their Unaffected Co-Twin Controls

Abstract

Background: Long-term survivors of young adult Hodgkin lymphoma (YAHL) are at risk of experiencing late effects due to cancer diagnosis and treatment. Many studies have compared survivors to unrelated controls from various sources, which could introduce confounding. Unaffected co-twins of cases are an ideal comparison because they are matched on many exposures, extending to in utero, are the same age and cohort, and are partially or completely matched on genome. Here we compare medical conditions, life milestones, lifestyle and behaviors, and psychological well-being in 35 long-term YAHL survivors and their unaffected co-twin controls(70 individual twins, 35 twin pairs) to obtain a more valid risk estimate of the contribution of the cancer and its treatment. Methods: Participants were enrolled in either the International Twin Study (national volunteer twin registry) or California Twin Program (population-based twin registry based on California birth certificates linked to the Department of Motor Vehicles) and completed online questionnaires including chronic health conditions, health behaviors, the achievement of developmental milestones (e.g., college degree attainment, employment, and having children), and life satisfaction. Twin comparisons were made using conditional logistical regression with p-values estimated using McNemar's test. Adjustment was not necessary as twins were mostly matched on potential confounders. All analyses were performed in STATA, version 17.0. Results: The mean age at diagnosis among survivors was 27 years (median: 26, range 16-48 years). The mean age at participation of survivors and unaffected co-twins was 56 years of age (median: 55, range: 40-74 years), with an average interval of 29 years between diagnosis and participation. 57% of YAHL survivors and 6% co-twin controls were female. 89% of participants were non-Hispanic white. 54% were monozygotic (MZ); 32% were like-sex dizygotic (DZ) and 14% were unlike-sex DZ. We observed significant increases in chronic medical conditions among YAHL survivors who were 4.33 times as likely to report a secondary malignancy as their unaffected co-twin controls (p=022). Breast cancer was the most commonly reported cancer, occurring in 8 survivors and one co-twin control (odds ratio [OR]=8.0, p= 0.05); all survivors with breast cancer had radiation therapy. Thyroid disease occurred in 23 survivors (18 had hypothyroidism) and 5 co-twin controls (OR=¥, p <0.001). Cardiovascular disease (any) occurred in 16 survivors and 5 co-twin controls (OR=12.0, p=0.017). Six survivors and no co-twin controls were affected with lung disease, mainly pulmonary fibrosis (p=0.031). After 29 years post-diagnosis, there were no significant differences between YAHL survivors and their twins with respect to healthcare utilization, substance use, physical activity, or developmental milestones relative to their unaffected co-twin. In particular, both twins had similar numbers of children and educational attainment. Life satisfaction was significantly lower among YAHL survivors (OR=¥, p=.043) but was unrelated to the occurrence of chronic conditions (p = 0.10). Conclusions: Decades after diagnosis, excess chronic conditions and lower life satisfaction were observed among YAHL survivors compared to their unaffected co-twin. The risk of cancer and chronic disease attributable to YAHL and its treatment is a more valid estimate when compared to unaffected co-twin controls of the survivors, who may also develop chronic conditions due to other factors in common. There were no differences in engagement in health behaviors or achievement of developmental milestones, potentially due to the importance of shared early-life experiences on these characteristics.