Table 2.

Multivariable model fits for STC rates in association with the standardized PRS and clinical risk factors in SJLIFE^a

Characteristics	Overall survivors			Survivors with neck-RT			Survivors without neck-RT
	RR	(95% CI)	P	RR	(95% CI)	P	RR	(95% CI)	P
Age at diagnosis, years
0–4	1.00	(Ref.)		1.00	(Ref.)		1.00	(Ref.)
5–9	0.28	(0.10–0.78)	0.015	0.26	(0.07–1.03)	0.06	0.33	(0.07–1.50)	0.15
10–14	1.20	(0.64–2.23)	0.58	1.46	(0.64–3.34)	0.37	0.67	(0.21–2.09)	0.49
≥15	0.61	(0.31–1.20)	0.15	0.74	(0.32–1.71)	0.49	0.47	(0.12–1.82)	0.28
Sex
Men	1.00	(Ref.)		1.00	(Ref.)		1.00	(Ref.)
Women	1.50	(0.89–2.53)	0.13	1.17	(0.63–2.17)	0.62	2.97	(1.05–8.39)	0.039
Treatment group
Anthracycline dose in the 2–3 tertiles with Epipodophyllotoxin without neck-RT	4.81	(1.83–12.65)	0.001	-			5.23	(1.82–15.03)	0.002
Neck-RT >0-<20 Gy without Epipodophyllotoxin	7.25	(2.08–25.32)	0.002	1.00	(Ref.)		-
Neck-RT ≥20-<30 Gy without Epipodophyllotoxin	14.55	(7.03–30.09)	<0.001	1.95	(0.60–6.36)	0.27	-
Neck-RT ≥30 Gy without Epipodophyllotoxin	5.61	(2.14–14.74)	<0.001	0.73	(0.19–2.76)	0.65	-
Neck-RT >0-<20 Gy with Epipodophyllotoxin	35.94	(10.20–126.56)	<0.001	4.52	(0.94–21.76)	0.06	-
Neck-RT ≥20-<30 Gy with Epipodophyllotoxin	28.50	(11.19–72.60)	<0.001	3.56	(0.96–13.19)	0.06	-
Neck-RT ≥30 Gy with Epipodophyllotoxin	13.32	(2.96–60.01)	<0.001	1.72	(0.29–10.13)	0.55	-
None of the above	1.00	(Ref.)						(Ref.)
Standardized PRSb, continuous (per one standard deviation)	1.57	(1.24–1.98)	<0.001	1.68	(1.29–2.18)	<0.001	1.36	(0.85–2.15)	0.24

Abbreviations: PRS (polygenic risk score), STC (subsequent thyroid cancer), RT (radiotherapy), RR (relative rate), and SJLIFE (St. Jude Lifetime Cohort Study).

^aAdjusted for attained age modeled by restricted cubic splines.

^bStandardized PRS was calculated as a weighted sum of the number of risk alleles carried by survivors and standardized by a mean of 0 and a SD of 1.