Table 3 Burden of APOBEC3-induced mutations in cases and controls from the NCI-Kaiser PaP cohort. Mutations are compared in CIN3+ cases vs. controls and for nonsynonymous (nonsyn) vs. synonymous (syn) mutations by variant allele fraction.

VAF	Parameter	Interpretation	Mutation burden^a	95% CI	P-value^d
Low^b	r_syn	Enrichment of synonymous mutations in cases vs. controls	0.68	(0.34–1.36)	0.28
	r_nonsyn	Enrichment of nonsynonymous mutations in cases vs. controls	0.71	(0.61–0.83)	1.2 × 10⁻⁵
	W	Selection of nonsynonymous mutations vs. synonymous mutations in controls	1.00	(0.70–1.44)	0.99
High^c	r_syn	Enrichment of synonymous mutations in cases vs. controls	1.27	(0.73–2.21)	0.40
	r_nonsyn	Enrichment of nonsynonymous mutations in cases vs. controls	0.82	(0.68–1.00)	0.05
	W	Selection of nonsynonymous mutations vs. synonymous mutations in controls	0.55	(0.35–0.85)	7.9 × 10⁻³

VAF variant allele fraction, CIN3+ cervical intraepithelial neoplasia grade 3 and cancer cases, CI confidence intervals.
^aMutation burden ratio of APOBEC3-induced mutations was calculated using a Poisson regression model to compare the mutation burden or enrichment of APOBEC3-induced mutations per virus between cases and controls for nonsynonymous and synonymous mutations (r); selection of nonsynonymous mutations in the controls was estimated adjusting for the number of cases and controls and the potential APOBEC3-mutable bases that result in nonsynonymous and synonymous mutations (w).
^bLow VAF is defined as VAF >10% and < = 60%.
^cHigh VAF is defined as VAF >60%.
^dP-values are generated by the Wald test of a Poisson regression model.

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