Lindsay A Williams1, Michaela Richardson1, Rebecca D Kehm2, Colleen C McLaughlin3, Beth A Mueller4, Eric J Chow4, Logan G Spector5. 1. Division of Epidemiology & Clinical Research, Department of Pediatrics, University of Minnesota, Minneapolis, MN, United States. 2. Department of Epidemiology, Mailman School of Public Health, Columbia University, NY, United States. 3. Albany College of Pharmacy and Health Sciences, Albany, NY, United States. 4. Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, WA, United States. 5. Division of Epidemiology & Clinical Research, Department of Pediatrics, University of Minnesota, Minneapolis, MN, United States; Masonic Cancer Center, University of Minnesota, Minneapolis, MN, United States. Electronic address: spector@umn.edu.
Abstract
BACKGROUND: Male sex is associated with an increased risk of childhood cancer as is high birthweight. Given that sex determination precedes birthweight we conducted a mediation analysis to estimate the direct effect of sex in association with childhood cancer tumor type with birthweight as the mediator. METHODS: Cases (n = 12,632) and controls (n = 64,439) (ages 0-14 years) were identified from population-based cancer and birth registries in Minnesota, New York, and Washington states (1970-2014). An inverse odds weighting (IOW) mediation analysis was used to estimate odds ratios (OR) and 95% confidence intervals (95% CI) as the measure of association between sex and cancer. RESULTS: A significant indirect effect was observed for sex and lymphoid leukemia, mediated by birthweight (indirectOR: 1.03; 95% CI: 1.02-1.04). We observed significant direct effects for male sex and lymphoid leukemia (directOR: 1.16; 95% CI: 1.08-1.25), Hodgkin lymphoma (directOR: 1.48; 95% CI: 1.22-1.81), Burkitt lymphoma (directOR: 5.02; 95% CI: 3.40-7.42), other non-Hodgkin lymphoma (directOR: 1.42; 95% CI: 1.18-1.70), intracranial embryonal tumors (directOR: 1.49; 95% CI: 1.26-1.76), hepatoblastoma (directOR: 1.90; 95% CI: 1.40-2.59), and rhabdomyosarcoma (directOR: 1.47; 95% CI: 1.19-1.81). There were also inverse associations for extracranial GCTs (directOR: 0.41; 95% CI: 0.26-0.63) and thyroid carcinoma (directOR: 0.35; 95% CI: 0.25-0.50). CONCLUSION: Significant direct effects for sex and numerous childhood cancer types suggests sex-specific factors such as differences in gene expression from the autosomes or the X chromosome, rather than birthweight, may underlie sex differences in tumor risk.
BACKGROUND: Male sex is associated with an increased risk of childhood cancer as is high birthweight. Given that sex determination precedes birthweight we conducted a mediation analysis to estimate the direct effect of sex in association with childhood cancertumor type with birthweight as the mediator. METHODS: Cases (n = 12,632) and controls (n = 64,439) (ages 0-14 years) were identified from population-based cancer and birth registries in Minnesota, New York, and Washington states (1970-2014). An inverse odds weighting (IOW) mediation analysis was used to estimate odds ratios (OR) and 95% confidence intervals (95% CI) as the measure of association between sex and cancer. RESULTS: A significant indirect effect was observed for sex and lymphoid leukemia, mediated by birthweight (indirectOR: 1.03; 95% CI: 1.02-1.04). We observed significant direct effects for male sex and lymphoid leukemia (directOR: 1.16; 95% CI: 1.08-1.25), Hodgkin lymphoma (directOR: 1.48; 95% CI: 1.22-1.81), Burkitt lymphoma (directOR: 5.02; 95% CI: 3.40-7.42), other non-Hodgkin lymphoma (directOR: 1.42; 95% CI: 1.18-1.70), intracranial embryonal tumors (directOR: 1.49; 95% CI: 1.26-1.76), hepatoblastoma (directOR: 1.90; 95% CI: 1.40-2.59), and rhabdomyosarcoma (directOR: 1.47; 95% CI: 1.19-1.81). There were also inverse associations for extracranial GCTs (directOR: 0.41; 95% CI: 0.26-0.63) and thyroid carcinoma (directOR: 0.35; 95% CI: 0.25-0.50). CONCLUSION: Significant direct effects for sex and numerous childhood cancer types suggests sex-specific factors such as differences in gene expression from the autosomes or the X chromosome, rather than birthweight, may underlie sex differences in tumor risk.
Authors: Kimberly R Kukurba; Princy Parsana; Brunilda Balliu; Kevin S Smith; Zachary Zappala; David A Knowles; Marie-Julie Favé; Joe R Davis; Xin Li; Xiaowei Zhu; James B Potash; Myrna M Weissman; Jianxin Shi; Anshul Kundaje; Douglas F Levinson; Philip Awadalla; Sara Mostafavi; Alexis Battle; Stephen B Montgomery Journal: Genome Res Date: 2016-04-21 Impact factor: 9.043
Authors: Tone Bjørge; Henrik Toft Sørensen; Tom Grotmol; Anders Engeland; Olof Stephansson; Mika Gissler; Steinar Tretli; Rebecca Troisi Journal: Pediatrics Date: 2013-10-28 Impact factor: 7.124
Authors: Lindsay A Williams; Michaela Richardson; Erin L Marcotte; Jenny N Poynter; Logan G Spector Journal: Pediatr Blood Cancer Date: 2019-02-28 Impact factor: 3.167
Authors: Erin L Marcotte; Jeremy M Schraw; Tania A Desrosiers; Wendy N Nembhard; Peter H Langlois; Mark A Canfield; Robert E Meyer; Sharon E Plon; Philip J Lupo Journal: JNCI Cancer Spectr Date: 2020-06-11
Authors: Logan G Spector; Aubrey K Hubbard; Brandon J Diessner; Mitchell J Machiela; Beau R Webber; Joshua D Schiffman Journal: Int J Cancer Date: 2021-05-17 Impact factor: 7.316