. 2021 Jul 28;114(1):109–122. doi: 10.1093/jnci/djab147

Table 3.

PRS interactions with age and BRCA1 and BRCA2 pathogenic variant characteristics for BRCA1 and BRCA2 carriers with breast cancer risk and prostate cancer risk.

Model and category	Breast cancer (PRS_ER+)^a				Prostate cancer (PRS_PC)
	BRCA1 carriers		BRCA2 carriers		BRCA1 carriers		BRCA2 carriers
	OR (95% CI)	P ^b	OR (95% CI)	P ^b	OR (95% CI)	P ^b	OR (95% CI)	P ^b
PRS x age interaction^c
PRS	1.88 (0.68 to 5.18)	.22	1.34 (0.71 to 2.53)	.37	0.64 (0.20 to 2.04)	.45	2.03 (0.91 to 4.52)	.08
PRS x age	1.00 (0.98 to 1.01)	.56	1.00 (0.99 to 1.01)	.98	1.02 (1.00 to 1.03)	.09	1.00 (0.98 to 1.01)	.55
P_LRT^d		.90		.86		.43		.79
Gene pathogenic variant class^e
Class I	1.38 (1.03 to 1.84)	.03	1.31 (1.13 to 1.52)	<.001	1.57 (1.13 to 2.19)	.008	1.57 (1.31 to 1.89)	<.001
Class II	1.71 (0.72 to 4.07)	.23	1.39 (0.67 to 2.86)	.38	3.00 (1.36 to 6.60)	.006	2.04 (0.63 to 6.55)	.23
P_LRT^d		.76		.69		.26		.97
BRCA1 pathogenic variant location (OCCR)
5’ to c.2281	1.50 (1.00 to 2.26)	.05	NA		NA		NA
c.2282 to c.4071	1.17 (0.79 to 1.72)	.44	NA		NA		NA
c.4072 to 3’	1.61 (0.87 to 2.98)	.13	NA		NA		NA
P_LRT^d		.85
BRCA2 pathogenic variant location (OCCR)
5’ to c.2830	NA		1.43 (1.09 to 1.88)	.009	NA		NA
c.2831 to c.6401	NA		1.24 (0.99 to 1.55)	.06	NA		NA
c.6402 to 3’	NA		1.33 (1.04 to 1.70)	.02	NA		NA
P_LRT^d				.61
BRCA2 pathogenic variant location (PCCR)
5’ to c.755	NA		NA		NA		1.67 (1.06 to 2.62)	.03
c.756 to c.1000	NA		NA		NA		1.77 (1.07 to 2.95)	.03
c.1001 to c.7913	NA		NA		NA		1.49 (1.18 to 1.89)	<.001
c.7914 to 3’	NA		NA		NA		1.76 (1.24 to 2.50)	.002
P_LRT^d								.52

^{^a}

The associations with breast cancer risk are reported for the ER-positive breast cancer PRS (PRS_ER+). CI = confidence interval; OCCR = ovarian cancer cluster region; OR = odds ratio per PRS standard deviation, estimated from a multinomial logistic regression; PCCR = prostate cancer cluster region; PRS = polygenic risk score; NA = not applicable.

^{^b}

P value was calculated using a 2-sided Wald test, unless otherwise indicated.

^{^c}

The PRS term is applicable at age 0 years and the PRS x age interaction term is a per-year effect. Age in years.

^{^d}

P values were calculated using a 2-sided likelihood ratio test. The likelihood ratio test compared the model that estimated the interaction term with a nested model that omitted the interaction term.

^{^e}

Class I pathogenic variant = loss-of-function pathogenic variants expected to result in unstable or no protein; class II pathogenic variant = pathogenic variants likely to yield stable mutant proteins.