Single nucleotide polymorphisms associated with risk for contralateral breast cancer in the Women's Environment, Cancer, and Radiation Epidemiology (WECARE) Study

Teraoka, Sharon N; Bernstein, Jonine L; Reiner, Anne S; Haile, Robert W; Bernstein, Leslie; Lynch, Charles F; Malone, Kathleen E; Stovall, Marilyn; Capanu, Marinela; Liang, Xiaolin; Smith, Susan A; Mychaleckyj, Josyf; Hou, Xuanlin; Mellemkjaer, Lene; Boice, John D; Siniard, Ashley; Duggan, David; Thomas, Duncan C

doi:10.1186/bcr3057

Table 1 Risk of contralateral breast cancer associated with radiation dose by single-nucleotide polymorphism genotype

From: Single nucleotide polymorphisms associated with risk for contralateral breast cancer in the Women's Environment, Cancer, and Radiation Epidemiology (WECARE) Study

		Homozygous; reference allele			Heterozygous			Homozygous; risk allele			Pvalue^e
SNP^a/gene region	RT dose^b	Cases^c (CBC)	Controls (UBC)	RR^d (95% CI)	Cases^c (CBC)	Controls (UBC)	RR^d (95% CI)	Cases^c (CBC)	Controls (UBC)	RR^d (95% CI)
rs2981582/FGFR2	0	93	75	1.0	139	119	1.0	66	39	1.0
	0 < 1.0	40	172	0.9 (0.6-1.5)	88	253	1.3 (0.9-1.9)	40	108	1.0 (0.6-1.8)	0.39
	1.0+	41	131	1.2 (0.8-2.0)	74	212	1.4 (1.0-2.1)	25	85	0.8 (0.4-1.4)
rs1219648/FGFR2	0	80	74	1.0	147	117	1.0	71	42	1.0
	0 < 1.0	40	165	1.1 (0.7-1.8)	85	256	1.2 (0.8-1.7)	44	112	1.1 (0.7-1.9)	0.37
	1.0+	34	124	1.3 (0.8-2.2)	79	216	1.4 (1.0-2.0)	27	89	0.8 (0.5-1.5)
rs3803662/TOX3	0	116	115	1.0	141	97	1.0	40	21	1.0
	0 < 1.0	85	238	1.6 (1.1-2.3)	66	242	0.9 (0.6-1.3)	17	52	0.9 (0.4-2.0)	0.07
	1.0+	63	199	1.5 (1.0-2.3)	57	175	1.1 (0.7-1.6)	19	54	0.8 (0.4-1.8)
rs13281615/8q24	0	89	67	1.0	141	128	1.0	70	39	1.0
	0 < 1.0	45	159	1.0 (0.6-1.6)	80	269	1.2 (0.9-1.7)	42	103	1.1 (0.6-1.9)	0.99
	1.0+	41	132	1.2 (0.7-2.0)	71	226	1.3 (0.9-1.8)	28	71	1.2 (0.6-2.1)
rs13387042/2q35	0	66	55	1.0	147	114	1.0	86	62	1.0
	0 < 1.0	31	118	1.1 (0.6-1.8)	75	259	1.1 (0.8-1.5)	61	155	1.3 (0.8-2.1)	0.45
	1.0+	34	107	1.1 (0.6-1.9)	59	202	1.1 (0.8-1.7)	46	120	1.4 (0.9-2.2)
rs11235127	0	205	162	1.0	81	66	1.0	13	5	1.0
/TMEM135	0 < 1.0	109	374	1.1 (0.8-1.5)	50	144	1.3 (0.8-2.1)	9	15	0.7 (0.2-3.1)	0.78
	1.0+	91	306	1.2 (0.9-1.6)	39	108	1.3 (0.8-2.3)	9	13	1.1 (0.3-4.3)
rs7313833/PTHLH	0	124	103	1.0	134	97	1.0	41	31	1.0
	0 < 1.0	57	232	1.0 (0.6-1.4)	83	257	1.1 (0.8-1.6)	27	40	2.3 (1.1-4.9)	0.42
	1.0+	56	194	1.1 (0.8-1.7)	62	185	1.2 (0.8-1.8)	21	45	1.7 (0.8-3.6)
rs7696175/4p14	0	114	72	1.0	127	110	1.0	58	51	1.0
	0 < 1.0	65	185	1.0 (0.7-1.6)	77	242	1.4 (1.0-2.0)	26	103	0.9 (0.5-1.7)	0.97
	1.0+	49	141	1.1 (0.7-1.7)	69	208	1.5 (1.0-2.1)	21	79	1.0 (0.5-1.8)
rs2107425/H19	0	132	96	1.0	137	110	1.0	29	27	1.0
	0 < 1.0	86	265	1.1 (0.8-1.6)	64	211	1.1 (0.7-1.6)	16	56	1.4 (0.6-3.1)	0.14
	1.0+	60	217	0.9 (0.6-1.4)	66	167	1.6 (1.1-2.3)	14	43	1.5 (0.6-3.5)

^aSingle-nucleotide polymorphisms (SNPs) that had a main effect on contralateral breast cancer (CBC) risk with a P value of less than 0.1 were selected for radiation therapy (RT) dose interaction analysis (rs2107425 did not meet this criterion but is included because of a report [36] that occupational radiation dose affects rs2107425-associated breast cancer risk). ^bRadiation dose to the contralateral breast (mean = 1.1 Gy) in the quadrant where the second primary tumor occurred. ^cTotal number of case subjects and matched control subjects for whom there were location-specific dose estimates ranged from 604 to 607 cases and 1,184 to 1,195 controls, depending on the number of genotyped subjects per SNP. ^dRate ratio (RR) adjusted for age at diagnosis of first primary tumor and the weighting factor that accounts for the counter-matched design. ^eOne degree of freedom trend test for modification of radiation dose effect by SNP genotype. CI, confidence interval; UBC, unilateral breast cancer.

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