Table 2.

Results of association analyses between the PRS₃₁₃ and contralateral breast cancer risk.

		BRCA1 heterozygotes (ER-negative PRS313)					BRCA2 heterozygotes (ER-positive PRS313)
		UBC cases, n	CBC cases, n	HRa	95% CI	P	UBC cases, n	CBC cases, n	HRa	95% CI	P
PRS continuous	All CBC	5,189	1,402	1.12	1.06–1.18	5.98×10-5	3,561	647	1.15	1.07–1.25	1.94×10-4
	Invasive CBC	5,324	1,267	1.13	1.07–1.20	3.15×10-5	3,663	545	1.15	1.06–1.25	6.02×10-4
Categorical PRS percentiles	0–5	260	48	0.81	0.59–1.11	0.188	166	28	1.06	0.71–1.58	0.782
	5–10	259	54	0.77	0.57–1.03	0.082	198	26	0.68	0.44–1.04	0.074
	10–20	519	131	0.94	0.76–1.15	0.544	355	51	0.91	0.66–1.25	0.554
	20–40	1,038	230	0.83	0.70–0.98	0.031	697	108	0.87	0.68–1.13	0.295
	40–60 (reference)	1,037	282	1.00			695	123	1.00
	60–80	1,038	313	1.04	0.88–1.22	0.664	734	128	0.96	0.75–1.23	0.748
	80–90	519	170	1.11	0.92–1.34	0.255	358	90	1.35	1.03–1.77	0.030
	90–95	259	82	1.18	0.92–1.51	0.185	178	46	1.35	0.96–1.90	0.082
	95–100	260	92	1.24	0.98–1.56	0.074	180	47	1.31	0.94–1.82	0.116
PRS*age BC1 continuous	Main effect	5,189	1,402	1.48	1.15–1.89	2.03×10-3	3,561	647	1.53	1.11–2.12	0.010
	Interaction effect			0.99	0.99–1.00	0.025			0.99	0.99–1.00	0.089
PRS effect per age group	<40	2,339	815	1.22	1.14–1.31	4.79×10-8	1,238	268	1.23	1.09–1.38	5.78×10-4
	40–50	1,821	456	0.99	0.90–1.09	0.785	1,306	261	1.19	1.05–1.34	6.91×10-3
	≥50	1,029	131	1.03	0.86–1.24	0.715	1,017	118	0.97	0.81–1.15	0.698
Variant classb	Class I	3,354	904	1.11	1.03–1.18	4.32×10-3	3,207	570	1.16	1.07–1.26	1.99×10-4
	Class II	1,345	374	1.15	1.04–1.28	4.75×10-3	125	25	0.91	0.65–1.28	0.594

BC1 first primary breast cancer, CBC contralateral breast cancer, CI confidence interval, HR hazard ratio, PRS polygenic risk score, UBC unilateral breast cancer.

^aHRs for association with breast cancer and the continuous PRS₃₁₃ are reported per standard deviation of the PRS in population-based controls.

^bClass I pathogenic variants result in an unstable or no protein. Class II pathogenic variants yield stable mutant proteins.