A genome-wide association study of contralateral breast cancer in the Women’s Environmental Cancer and Radiation Epidemiology Study

Table 1 Associations of weighted polygenic risk score comprised of known breast cancer susceptibility SNPs with contralateral breast cancer risk

PRS	CBCs No. (%)	UBCs No. (%)	RR^a	95% CI^a	P^a
Without proxies, 239 SNPs
Continuous weighted PRS	1017 (100)	1466 (100)	1.46	1.25–1.71	< 0.0001
Weighted PRS per Standard Deviation	1017 (100)	1466 (100)	1.25	1.14–1.36	< 0.0001
Median of weighted PRS
Below median	415 (40.8)	733 (50)	Ref	Ref
Above median	602 (59.2)	733 (50)	1.42	1.19–1.69	0.0001
Quartile of weighted PRS
Quartile 1	192 (18.9)	366 (25)	Ref	Ref	Ref
Quartile 2	223 (21.9)	367 (25)	1.03	0.79–1.33	0.85
Quartile 3	260 (25.6)	366 (25)	1.27	0.99–1.63	0.06
Quartile 4	342 (33.6)	367 (25)	1.61	1.25–2.07	0.0002
With proxies, 257 SNPs
Continuous weighted PRS	1017 (100)	1466 (100)	1.39	1.19–1.61	< 0.0001
Weighted PRS per standard deviation	1017 (100)	1466 (100)	1.22	1.11–1.33	< 0.0001
Median of weighted PRS
Below median	416 (40.9)	733 (50)	Ref	Ref
Above median	601 (59.1)	733 (50)	1.41	1.19–1.68	0.0001
Quartile of weighted PRS
Quartile 1	211 (20.7)	367 (25)	Ref	Ref
Quartile 2	205 (20.2)	366 (25)	0.87	0.67–1.12	0.28
Quartile 3	256 (25.2)	367 (25)	1.14	0.89–1.46	0.32
Quartile 4	345 (33.9)	366 (25)	1.50	1.18–1.92	0.001

Non-Hispanic white women only, WECARE I and WECARE II Studies combined
CBC, contralateral breast cancer; CI, confidence interval; No., number; PRS, polygenic risk score; RR, rate ratio; UBC, unilateral breast cancer
^aAdjusted for the top five principal components, age at first breast cancer diagnosis, age at menarche, age at menopause, number of full-term pregnancies, stage of first breast cancer, histology of first breast cancer, family history of breast cancer, chemotherapy, and hormone therapy

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