The association between sex and most childhood cancers is not mediated by birthweight

Lindsay A. Williams, Michaela R Richardson, Rebecca D. Kehm, Colleen C. McLaughlin, Beth A. Mueller, Eric J. Chow, Logan G Spector

Research output: Contribution to journalArticle

2 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)7-12
Number of pages6
JournalCancer Epidemiology
Volume57
DOIs
StatePublished - Dec 2018

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Confidence Intervals
Neoplasms
Lymphoid Leukemia
Hepatoblastoma
Sex Factors
Burkitt Lymphoma
Rhabdomyosarcoma
X Chromosome
Hodgkin Disease
Thyroid Neoplasms
Sex Characteristics
Non-Hodgkin's Lymphoma
Registries
Odds Ratio
Parturition
Gene Expression
Population

Keywords

  • Birthweight
  • Childhood cancer
  • Mediation analysis
  • Sex-disparity

Cite this

The association between sex and most childhood cancers is not mediated by birthweight. / Williams, Lindsay A.; Richardson, Michaela R; Kehm, Rebecca D.; McLaughlin, Colleen C.; Mueller, Beth A.; Chow, Eric J.; Spector, Logan G.

In: Cancer Epidemiology, Vol. 57, 12.2018, p. 7-12.

Research output: Contribution to journalArticle

Williams, Lindsay A. ; Richardson, Michaela R ; Kehm, Rebecca D. ; McLaughlin, Colleen C. ; Mueller, Beth A. ; Chow, Eric J. ; Spector, Logan G. / The association between sex and most childhood cancers is not mediated by birthweight. In: Cancer Epidemiology. 2018 ; Vol. 57. pp. 7-12.
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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.",
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T1 - The association between sex and most childhood cancers is not mediated by birthweight

AU - Williams, Lindsay A.

AU - Richardson, Michaela R

AU - Kehm, Rebecca D.

AU - McLaughlin, Colleen C.

AU - Mueller, Beth A.

AU - Chow, Eric J.

AU - Spector, Logan G

PY - 2018/12

Y1 - 2018/12

N2 - 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.

AB - 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.

KW - Birthweight

KW - Childhood cancer

KW - Mediation analysis

KW - Sex-disparity

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