Reproductive aging-associated common genetic variants and the risk of breast cancer

He, Chunyan; Chasman, Daniel I; Dreyfus, Jill; Hwang, Shih-Jen; Ruiter, Rikje; Sanna, Serena; Buring, Julie E; Fernández-Rhodes, Lindsay; Franceschini, Nora; Hankinson, Susan E; Hofman, Albert; Lunetta, Kathryn L; Palmieri, Giuseppe; Porcu, Eleonora; Rivadeneira, Fernando; Rose, Lynda M; Splansky, Greta L; Stolk, Lisette; Uitterlinden, André G; Chanock, Stephen J; Crisponi, Laura; Demerath, Ellen W; Murabito, Joanne M; Ridker, Paul M; Stricker, Bruno H; Hunter, David J

doi:10.1186/bcr3155

Breast Cancer Research

Table 2 Association of candidate single-nucleotide polymorphism loci and the risk of breast cancer

From: Reproductive aging-associated common genetic variants and the risk of breast cancer

SNP	Gene(s)^a	Distance from gene	Chromosome	Position (Build 36)	Risk/Reference alleles^b	Effect allele	Allele frequency^c of cases/controls^d	Effect	SE	OR (95% CI)^e	Pvalue^f	Direction^g	Pvalue for heterogeneity^h
Age at menarche
rs1079866	INHBA	~250 kb	7	41436618	C/G	c	0.87/0.85	0.132	0.044	1.14 (1.05-1.24)	0.003	++--+-	0.37
rs7821178	PXMP3	~181 kb	8	78256392	A/C	a	0.35/0.33	0.081	0.031	1.08 (1.02-1.15)	0.009	++--++	0.43
rs7642134	VGLL3	~70 kb	3	86999572	A/G	a	0.39/0.38	0.058	0.03	1.06 (1.00-1.12)	0.056	++++-+	0.83
rs10980926	ZNF483	Intronic	9	113333455	G/A	g	0.64/0.65	-0.057	0.031	0.94 (0.89-1.00)	0.066	---+--	0.58
rs1398217	FUSSEL18	Intronic	18	43006236	G/C	g	0.42/0.42	0.048	0.03	1.05 (0.99-1.11)	0.10	++-+++	0.40
rs17188434	NR4A2	~84 kb	2	156805022	C/T	c	0.07/0.07	0.075	0.059	1.08 (0.96-1.21)	0.20	+++---	0.34
rs13187289	PHF15	~12 kb	5	133877076	C/G	c	0.80/0.80	-0.038	0.038	0.96 (0.89-1.04)	0.32	---+-+	0.03
rs12617311	PLCL1	~195 kb	2	199340810	A/G	a	0.32/0.32	-0.032	0.033	0.97 (0.91-1.03)	0.33	--+-+-	0.81
rs17268785	CCDC85A	Intronic	2	56445587	A/G	a	0.84/0.84	0.037	0.041	1.04 (0.96-1.12)	0.37	-+-+++	0.89
rs2002675	TRA2B, ETV5	~4 kb, ~135 kb	3	187112262	A/G	a	0.58/0.57	0.022	0.03	1.02 (0.96-1.08)	0.47	++++--	0.92
rs466639	RXRG	Intronic	1	163661506	T/C	t	0.12/0.12	-0.032	0.046	0.97 (0.89-1.06)	0.49	-+-+--	0.35
rs1659127	MKL2	~28 kb	16	14295806	G/A	g	0.67/0.66	0.022	0.033	1.02 (0.96-1.09)	0.50	+++++-	0.28
rs9635759	CA10	~94 kb	17	46968784	G/A	g	0.69/0.70	-0.021	0.034	0.98 (0.92-1.05)	0.54	-+--+-	0.32
rs10899489	GAB2	Intronic	11	77773021	C/A	c	0.85/0.84	0.025	0.041	1.03 (0.95-1.11)	0.54	++++--	0.97
rs10423674	CRTC1	Intronic	19	18678903	C/A	c	0.67/0.67	0.017	0.032	1.02 (0.96-1.08)	0.59	+++-+-	0.60
rs7759938	LIN28B	~26 kb	6	105485647	T/C	t	0.69/0.69	-0.017	0.032	0.98 (0.92-1.05)	0.60	+-+---	0.53
rs2090409	TMEM38B	~400 kb	9	108006909	A/C	a	0.33/0.33	0.012	0.031	1.01 (0.95-1.08)	0.69	--++-+	0.21
rs6438424	3q13.32	Intergenic	3	119057512	A/C	a	0.50/0.50	0.002	0.029	1.00 (0.95-1.06)	0.94	---+++	0.88
rs6589964	BSX	~18 kb	11	122375893	A/C	a	0.48/0.48	-0.001	0.031	1.00 (0.94-1.06)	0.99	--++++	0.20
Age at natural menopause
rs2517388	ASH2L	Intronic	8	38096889	G/T	g	0.17/0.16	0.096	0.042	1.10 (1.01-1.20)	0.023	+++-+-	0.08
rs4693089	HEL308	Intronic	4	84592646	G/A	g	0.47/0.48	-0.06	0.031	0.94 (0.89-1.00)	0.054	------	0.38
rs11668344	TMEM150B	Intronic	19	60525476	A/G	a	0.64/0.64	-0.049	0.03	0.95 (0.90-1.01)	0.11	+-----	0.02
rs2307449	POLG	Intronic	15	87664932	T/G	t	0.60/0.61	-0.045	0.031	0.96 (0.90-1.02)	0.15	-+--+-	0.20
rs16991615	MCM8	Missense	20	5896227	A/G	a	0.07/0.06	0.079	0.06	1.08 (0.96-1.22)	0.18	+++--+	0.80
rs12294104	C11orf46, PPED2	~24 kb,~49 kb	11	30339475	T/C	t	0.17/0.17	0.046	0.039	1.05 (0.97-1.13)	0.24	++-++-	0.56
rs12461110	NLRP11	Missense	19	61012475	G/A	g	0.64/0.65	-0.036	0.031	0.96 (0.91-1.03)	0.24	--++-+	0.32
rs2303369	FNDC4	Intronic	2	27568920	C/T	c	0.62/0.63	-0.031	0.03	0.97 (0.91-1.03)	0.31	--++-+	0.22
rs4886238	TDRD3	Intronic	13	60011740	A/G	a	0.35/0.34	0.029	0.031	1.03 (0.97-1.09)	0.35	++----	0.79
rs2277339	PRIM1	Missense	12	55432336	T/G	t	0.90/0.89	0.037	0.05	1.04 (0.94-1.14)	0.46	++++--	0.47
rs10852344	GSPT1, TNFRSF17	~7 kb, ~42 kb	16	11924420	C/T	c	0.41/0.41	0.020	0.030	1.02 (0.96-1.08)	0.50	++--++	0.87
rs10183486	TLK1	Intronic	2	171699217	C/T	c	0.62/0.62	-0.015	0.031	0.99 (0.93-1.05)	0.63	--+--+	0.98
rs4246511	RHBDL2	Intronic	1	39152972	T/C	t	0.27/0.27	0.016	0.035	1.02 (0.95-1.09)	0.66	++---+	0.69
rs2153157	SYCP2L	Intronic	6	11005474	A/G	a	0.50/0.50	0.011	0.029	1.01 (0.96-1.07)	0.70	++-+-+	0.59
rs1635501	EXO1	Intronic	1	240107398	T/C	t	0.53/0.52	0.011	0.034	1.01 (0.95-1.08)	0.74	+-+--+	0.31
rs365132	UIMC1	Synonymous	5	176311180	T/G	t	0.50/0.50	-0.009	0.03	0.99 (0.93-1.05)	0.76	+-+--+	0.58
rs1046089	BAT2	Missense	6	31710946	G/A	g	0.65/0.65	-0.008	0.031	0.99 (0.93-1.05)	0.79	-+-+-+	0.24
Breast cancer
rs2981582	FGFR2	Intronic	10	123342307	A/G	a	0.44/0.38	0.188	0.03	1.21 (1.14-1.28)	4.7 × 10^-10	++++++	0.10
rs3803662	TOX3	~6 kb	16	51143842	A/G	a	0.31/0.25	0.166	0.032	1.18 (1.11-1.26)	2.6 × 10^-7	++++-+	0.31
rs11249433	FCGR1B	~245 kb	1	120982136	G/A	g	0.44/0.46	0.149	0.031	1.16 (1.09-1.23)	1.9 × 10^-6	+++++-	0.26
rs7716600	MRPS30	~59 kb	5	44910762	A/C	a	0.24/0.20	0.148	0.035	1.16 (1.08-1.24)	2.3 × 10^-5	++++++	0.80
rs13387042	TNP1	~181 kb	2	217614077	A/G	a	0.55/0.50	0.114	0.029	1.12 (1.06-1.19)	1.0 × 10^-4	++-+++	0.20
rs889312	MAP3K1	~43 kb	5	56067641	C/A	c	0.30/0.32	0.122	0.032	1.13 (1.06-1.20)	1.5 × 10^-4	++++++	0.65
rs13281615	8q24.21	Intergenic	8	128424800	G/A	g	0.43/0.50	0.107	0.03	1.11 (1.05-1.18)	3.0 × 10^-4	++++--	0.01
rs999737	RAD51L1	Intronic	14	68104435	C/T	c	0.77/0.80	0.079	0.035	1.08 (1.01-1.16)	0.024	++++-+	0.31
rs3817198	LSP1	Intronic	11	1865582	C/T	c	0.32/0.34	0.049	0.032	1.05 (0.99-1.12)	0.13	+++-++	0.45
rs1045485	CASP8	Missense	2	201857834	G/C	g	0.88/0.92	0.067	0.045	1.07 (0.98-1.17)	0.13	++--++	0.75

^aNearest gene(s); ^bthe risk allele refers to the allele associated with a younger age at menarche, an older age at natural menopause, or an increased risk of breast cancer; ^ceffect allele frequency; ^deffect allele frequency in case or control subjects, respectively; ^eper effect allele change in log odds ratio (OR) of breast cancer; ^fP value from meta-analysis with additive genetic coding after adjustment for age and top genetic principle components; ^gdirection of effect allele association with breast cancer in the six studies in order: Nurses' Health Study, Women's Genome Health Study, SardiNIA Breast Cancer Study, Rotterdam Study I and II, Framingham Heart Study, and Atherosclerosis Risk in Communities Study; ^hP value from heterogeneity test across studies with 5 degrees of freedom. CI, confidence interval; SE, standard error; SNP, single-nucleotide polymorphism.

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