Genetic Polymorphisms in the Estrogen Receptor α Gene and Risk of Breast Cancer: Results from the Shanghai Breast Cancer Study

Qiuyin Cai; Xiao-Ou Shu; Fan Jin; Qi Dai; Wanqing Wen; Jia-Rong Cheng; Yu-Tang Gao; Wei Zheng

DOI: Published September 2003

Article Figures & Data

Tables

Table 1

Comparison of cases and controls by selected demographic factors and major risk factors for breast cancer from the Shanghai Breast Cancer Study, 1996–1998

	Subjects included in whole study			Subjects with genotying data			P
		Cases (n = 1459) (1)	Controls (n = 1556) (2)	Cases (n = 1069) (3)	Controls (n = 1166) (4)	Case (3 versus 1)	Control (4 versus 2)	Case versus control (3 versus 4)
Demographic factors
Age (yr)^a	47 (42, 53)	46 (40, 54)	47 (42, 53)	46 (40, 54)	0.088	0.666	0.230
Education ≥ high school, %	45.2	44.3	43.7	42.7	0.346	0.274	0.642
Major risk factor
First-degree relative with breast cancer, %	3.7	2.4	3.3	2.3	0.510	0.853	0.168
Ever diagnosed with breast fibroadenoma, %	9.6	5.0	9.9	5.2	0.759	0.783	<0.001
Smoking, %	2.6	2.5	2.4	2.7	0.797	0.811	0.734
Drinking, %	4.0	4.1	3.4	4.0	0.298	0.921	0.464
Hormone replacement therapy, %	2.9	2.7	2.7	2.5	0.788	0.721	0.838
No regular leisure physical activity, %	81.3	74.8	80.9	74.4	0.782	0.758	<0.001
WHR^a	0.81 (0.77, 0.84)	0.80 (0.76, 0.84)	0.81 (0.77, 0.84)	0.80 (0.76, 0.83)	0.209	0.495	<0.001
WHR >0.84, %	26.7	21.3	26.3	20.6	0.769	0.554	0.001
BMI^a	23.2 (21.2, 25.5)	22.8 (20.7, 25.1)	23.1 (21.2, 25.6)	22.9 (20.8, 25.2)	0.892	0.296	0.035
≥25, %	30.4	25.8	31.0	26.9	0.694	0.412	0.036
Age at menarche (yr)^a	14 (13, 16)	15 (13, 16)	14 (13, 16)	15 (13, 16)	0.650	0.596	0.001
Age at menarche ≤13 yr, %	31.6	26.5	31.6	25.9	0.981	0.637	0.003
Premenopausal, %	65.5	63.8	67.2	64.1	0.263	0.824	0.130
Age at menopause ≥50 yr^b, %	40.5	37.2	41.0	37.2	0.906	0.966	0.282
No live birth, %	5.1	3.9	4.9	4.1	0.811	0.787	0.393
Age at first live birth ≥30 yr^a, %	22.2	16.5	22.0	16.3	0.900	0.906	<0.001
Calorie intake (Kcal)^a	1796 (1541, 2128)	1782 (1529, 2075)	1795 (1536, 2132)	1784 (1535, 2087)	0.994	0.678	0.278
Fat (g)^a	32.9 (25.0, 43.5)	32.5 (24.6, 43.2)	33.1 (24.9, 44.0)	32.5 (24.5, 43.0)	0.787	0.958	0.088
Protein (g)^a	73.5 (60.2, 91.0)	71.9 (59.5, 87.1)	73.3 (60.2, 91.0)	71.8 (59.1, 87.0)	0.737	0.969	0.013
Carbohydrate (g)^a	313.0 (272.7, 366.1)	310.2 (269.8, 360.0)	313.9 (272.8, 366.5)	312.9 (270.3, 361.5)	0.999	0.534	0.852

^a Median (25^th, 75^th percentile) are presented, P were derived from test.
^b Among postmenopausal women.
^c Among parous women.

Table 2

Polymorphisms of ER-αPvuII and XbaI and breast cancer risk, Shanghai Breast Cancer Study, 1996–1998

	Case (%) (n = 1069)	Control (%) (n = 1166)	OR^a	95% CI	FAR 95% CI
PvuII
PP	12.9	16.3	1.0	(ref)^b
Pp/pp	87.1	83.7	1.4	(1.1–1.7)
Pp	48.3	46.8	1.3	(1.0–1.7)	(1.2–1.5)
pp	38.8	36.9	1.4	(1.1–1.8)	(1.2–1.6)
Trend test			P = 0.042
XbaI
XX	3.4	4.2	1.0	(ref)
Xx/xx	96.6	95.8	1.2	(0.8–1.9)
Xx	46.5	43.6	1.3	(0.8–2.0)	(1.1–1.4)
xx	50.1	52.3	1.2	(0.7–1.8)	(1.0–1.3)
Trend test			P = 0.660
PvuII and XbaI
PPXX	2.7	3.2	1.0	(ref)
PPXx	8.0	9.5	1.0	(0.6–1.7)	(0.7–1.3)
PPxx	2.3	3.7	0.7	(0.3–1.4)	(0.4–1.2)
PpXX	0.6	0.7	1.0	(0.3–3.4)	(0.4–3.0)
PpXx	27.9	27.2	1.2	(0.7–2.0)	(1.0–1.4)
Ppxx	19.7	18.8	1.3	(0.7–2.1)	(1.0–1.5)
ppXX	0	0	-
ppXx	10.6	7.3	1.7	(1.0–3.1)	(1.3–2.3)
ppxx	28.2	29.6	1.1	(0.7–1.9)	(1.0–1.3)

^a Adjusted for age.
^b ref., reference.

Table 3

Polymorphisms of ER-α PvuII and XbaI and breast cancer risk by age at diagnosis and menopausal status, Shanghai Breast Cancer Study, 1996–1998

	Age ≤45									Age >45
		Case % (n = 471)	Control % (n = 558)	OR^a	95% CI	FAR 95% CI	Case % (n = 598)	Control % (n = 608)	OR^a	95% CI	FAR 95% CI
PvuII
PP	12.2	15.5	1.0	(ref)^b		13.5	17.1	1.0	(ref)
Pp/pp	87.8	84.5	1.4	(1.0–2.0)		86.5	82.9	1.3	(1.0–1.8)
Pp	46.7	48.2	1.3	(0.9–1.9)	(1.1–1.5)	49.7	45.5	1.4	(1.0–1.9)	(1.2–1.6)
pp	41.2	36.4	1.5	(1.0–2.2)	(1.2–1.9)	36.9	37.4	1.3	(0.9–1.8)	(1.0–1.5)
Trend test			P = 0.036					P = 0.406
XbaI
XX	4.1	4.5	1.0	(ref)		2.9	3.8	1.0	(ref)
Xx/xx	95.9	95.5	1.1	(0.6–2.0)		97.1	96.2	1.4	(0.7–2.6)
Xx	48.6	43.1	1.2	(0.6–2.3)	(1.0–1.5)	44.8	44.0	1.4	(0.7–2.6)	(1.1–1.6)
xx	47.3	52.3	1.0	(0.5–1.8)	(0.8–1.2)	52.4	52.2	1.4	(0.7–2.6)	(1.2–1.6)
Trend test			P = 0.203					P = 0.548

	Premenopausal									Postmenopausal
		Case % (n = 715)	Control % (n = 746)	OR^a	95% CI	FAR 95% CI	Case % (n = 349)	Control % (n = 417)	OR^a	95% CI	FAR 95% CI
PvuII
PP	13.0	15.9	1.0	(ref)		12.9	17.0	1.0	(ref)
Pp/pp	87.0	84.1	1.3	(1.0–1.8)		87.1	83.0	1.4	(0.9–2.1)
Pp	47.6	47.6	1.3	(0.9–1.8)	(1.1–1.5)	50.0	45.3	1.4	(0.9–2.2)	(1.2–1.8)
pp	39.4	36.5	1.4	(1.0–1.9)	(1.2–1.7)	37.1	37.7	1.3	(0.8–2.0)	(1.0–1.7)
Trend test			P = 0.057					P = 0.448
XbaI
XX	3.6	4.1	1.0	(ref)		2.9	4.1	1.0	(ref)
Xx/xx	96.4	95.9	1.0	(0.6–1.8)		97.1	95.9	1.5	(0.7–3.3)
Xx	47.8	44.9	1.1	(0.6–1.9)	(1.0–1.3)	43.8	41.4	1.5	(0.7–3.5)	(1.2–1.9)
xx	48.5	51.0	1.0	(0.6–1.7)	(0.9–1.2)	53.3	54.5	1.4	(0.6–3.3)	(1.2–1.8)
Trend test	P = 0.456							P = 0.899

^a Adjusted for age.
^b ref, reference.

Table 4

Polymorphisms of ER-α PvuII and XbaI and breast cancer risk by selected estrogen exposure-related factors and lifestyle factors, Shanghai Breast Cancer Study, 1996–1998

	PvuII polymorphism							XbaI polymorphism
		PP			Pp or pp			XX		Xx or xx
		Case/control	OR^a (95% CI)	Case/control	OR^a (95% CI)	Case/control	OR^a (95% CI)	Case/control	OR^a (95% CI)
Age at menarche (yr)
≤13	98/140	1.0 (ref)	619/707	1.3 (1.0–1.7)	29/37	1.0 (ref)^b	698/813	1.1 (0.6–1.8)
>13	38/47	1.0 (ref)	298/250	1.5 (1.0–2.4)	7/11	1.0 (ref)	327/289	1.5 (0.6–4.1)
Age at menopause (yr)^c
<50	26/45	1.0 (ref)	176/209	1.4 (0.8–2.4)	7/13	1.0 (ref)	196/246	1.5 (0.6–3.9)
≥50	18/24	1.0 (ref)	122/128	1.3 (0.7–2.4)	3/4	1.0 (ref)	139/148	1.3 (0.3–5.7)
Years of menstruation^d
<Median (30 yr)	54/85	1.0 (ref)	396/470	1.4 (0.9–2.0)	19/26	1.0 (ref)	431/538	1.0 (0.6–1.9)
≥Median (30 yr)	82/102	1.0 (ref)	523/489	1.3 (1.0–1.8)	17/22	1.0 (ref)	596/566	1.4 (0.7–2.6)
Ever diagnosed with breast fibroadenoma
No	119/179	1.0 (ref)	830/906	1.4 (1.1–1.8)	32/46	1.0 (ref)	924/1046	1.2 (0.8–2.0)
Yes	16/8	1.0 (ref)	89/53	0.9 (0.4–2.2)	4/2	1.0 (ref)	102/58	0.9 (0.2–5.0)
BMI
<25	93/136	1.0 (ref)	635/706	1.4 (1.0–1.8)	29/34	1.0 (ref)	704/807	1.0 (0.6–1.6)
≥25	43/51	1.0 (ref)	284/253	1.3 (0.9–2.1)	7/14	1.0 (ref)	323/297	2.1 (0.9–5.4)
BMI^c
<25	22/43	1.0 (ref)	168/211	1.6 (0.9–2.7)	6/10	1.0 (ref)	185/245	1.4 (0.5–3.8)
≥25	22/26	1.0 (ref)	130/126	1.3 (0.7–2.4)	4/7	1.0 (ref)	150/149	1.8 (0.5–6.4)
WHR
≤0.84	102/154	1.0 (ref)	674/757	1.4 (1.0–1.8)	27/38	1.0 (ref)	756/878	1.2 (0.7–2.0)
>0.84	34/33	1.0 (ref)	245/202	1.2 (0.7–2.0)	9/10	1.0 (ref)	271/226	1.3 (0.5–3.2)
Regular exercise during past 10 years
Yes	26/56	1.0 (ref)	176/240	1.5 (0.9–2.6)	4/8	1.0 (ref)	199/286	1.3 (0.4–4.3)
No	110/131	1.0 (ref)	742/719	1.3 (1.0–1.7)	32/40	1.0 (ref)	827/818	1.2 (0.8–2.0)
Caloric intake
<Medium	64/94	1.0 (ref)	452/484	1.4 (1.0–1.9)	17/24	1.0 (ref)	505/556	1.3 (0.7–2.5)
≥Medium	72/93	1.0 (ref)	467/475	1.3 (1.0–1.9)	19/24	1.0 (ref)	522/548	1.1 (0.6–2.0)
Fat intake
<Medium	62/83	1.0 (ref)	436/490	1.2 (0.8–1.7)	16/26	1.0 (ref)	489/550	1.5 (0.8–2.8)
≥Medium	74/104	1.0 (ref)	483/469	1.5 (1.1–2.1)	20/22	1.0 (ref)	538/554	1.0 (0.6–1.9)
Protein intake
<Medium	60/95	1.0 (ref)	440/482	1.4 (1.0–2.0)	17/26	1.0 (ref)	489/553	1.4 (0.7–2.5)
≥Medium	76/92	1.0 (ref)	479/477	1.3 (0.9–1.8)	19/22	1.0 (ref)	538/551	1.1 (0.6–2.0)
Carbohydrate intake
<Medium	62/98	1.0 (ref)	458/480	1.5 (1.0–2.1)	20/19	1.0 (ref)	505/556	0.9 (0.5–1.6)
≥Medium	74/89	1.0 (ref)	461/479	1.2 (0.9–1.7)	16/29	1.0 (ref)	522/548	1.6 (0.9–3.0)

^a Adjusted for age.
^b ref, reference.
^c Among postmenopausal women only.
^d Years of menstruation = menopausal age or age at interview for premenopausal women − menarche age.

Table 5

Association of ER-α PvuII and XbaI polymorphisms with ER/PR status among breast cancer patients, Shanghai Breast Cancer Study, 1996–1998

	PvuII (%)					XbaI (%)
		PP	Pp	pp	XX	Xx	xx
ER status
Positive	13.5	48.6	37.9	3.0	46.0	51.0
Negative	12.8	45.0	42.2	3.1	48.1	48.8
	P = 0.516			P = 0.857
PR status
Positive	14.4	46.6	39.0	2.7	46.5	50.8
Negative	11.6	48.2	40.2	3.6	47.0	49.4
	P = 0.599			P = 0.788
ER/PR status
Both positive	14.6	48.3	37.1	3.0	46.3	50.7
One positive	10.9	43.8	45.3	2.1	46.1	51.8
Both negative	12.6	47.5	39.9	3.8	48.1	48.1
Unknown	23.8	50.4	37.5	4.0	46.0	50.0
	P = 0.639			P = 0.940