Case–control study of breast cancer and exposure to synthetic environmental chemicals among Alaska Native women

Figures & data

Table I. Statistics for characteristics and known risk factors for breast cancer of enrolled Alaska Native women (n=170), 1999–2002

	Total^a	Case	Control	p^b
Number of women	170	75	95	–
Mean age at enrolment in years (range)	51 (30–88)	53 (30–78)	50 (30–88)	0.08
Mean age at menarche in years (range)	13 (9–19)	13 (9–19)	13 (10–17)	0.68
	Result n (%)
Ethnicity
Eskimo	93 (54.7)	36 (48.0)	57 (60.0)	0.06
Indian	37 (21.8)	22 (29.3)	15 (15.8)
Aleut	27 (15.9)	9 (12.0)	18 (19.0)
Other	13 (7.6)	8 (10.7)	5 (5.3)
Service units by region at birth
South central (Anchorage)	33 (19.6)	15 (20.3)	18 (19.1)	0.08
Interior (Fairbanks)	8 (4.8)	3 (4.1)	5 (5.3)
Northwest (Barrow, Kotzebue, Nome)	46 (27.4)	17 (23.0)	29 (30.9)
Southwest (Bethel & Dillingham)	44 (26.2)	16 (21.6)	28 (29.8)
Southeast (Sitka–Mt. Edgecumbe; Annette Isl)	17 (10.1)	13 (17.6)	4 (4.3)
Other	20 (12.0)	10 (13.5)	10 (10.6)
Service units by region at time of enrolment
South central (Anchorage)	99 (58.2)	42 (56.0)	57 (60.0)	NA
Interior (Fairbanks)	2 (1.2)	1 (1.3)	1 (1.0)
Northwest (Barrow, Kotzebue, Nome)	32 (18.8)	14 (18.7)	18 (19.0)
Southwest (Bethel & Dillingham)	26 (15.3)	7 (9.3)	19 (20.0)
Southeast (Sitka–Mt. Edgecumbe; Annette Isl)	10 (5.9)	10 (13.3)	0
Other	1 (0.6)	1 (1.3)	0
Highest education level completed
≤8th grade	27 (15.9)	11 (14.7)	16 (16.8)	0.45
9th–11th	18 (10.6)	5 (6.7)	13 (13.7)
High school graduate	109 (64.1)	52 (69.3)	57 (60.0)
≥College graduate	16 (9.4)	7 (9.3)	9 (9.5)
Smoking (yes)
Ever	132 (77.7)	62 (82.7)	70 (73.7)	0.20
Current (n=135)	80 (59.3)	33 (51.6)	47 (66.2)	0.11
Alcohol (yes)
Ever	153 (90.0)	71 (94.7)	82 (86.3)	0.08
Current (n=154)	79 (51.3)	34 (47.9)	45 (54.2)	0.52
Family history of breast cancer (yes)
Mother	7 (4.1)	3 (4.0)	4 (4.2)	0.58
Maternal grandmother	7 (4.1)	4 (5.3)	3 (3.2)	0.29
Paternal grandmother	4 (2.4)	2 (2.7)	2 (2.1)	0.91
Sister	10 (5.9)	3 (5.0)	7 (9.1)	0.51
Daughters	2 (1.2)	0	2 (2.9)	0.50
Pregnancies (yes)
Ever (n=169)	158 (93.5)	71 (96.0)	87 (91.6)	0.35
Live births
Median # births (range)	3 (0–11)	3 (0–10)	3 (0–11)	0.77
Number of women (%)	157 (92.4)	71 (96.0)	86 (90.5)	0.23
Breast fed
Median cumulative months (range)	4 (0–216)	2 (0–88)	8 (0–216)	0.05
Number of women (%)	106 (62.4)	45 (60.0)	61 (64.2)	0.63
Hormone history (yes)
Ever birth control pills	111 (66.9)	49 (65.3)	62 (68.1)	0.74
Ever hormones	62 (36.9)	25 (33.8)	37 (39.4)	0.52
Menopausal status (yes)
# Women not expecting more periods/who are menopausal (%)	87 (53.7)	46 (63.9)	41 (45.6)	0.03

^aDue to missing responses, sums do not always equal to 170. Where this was the case, percentages were calculated using the number of women answering the question.

^bP-values represent comparison between cases and controls, using t-tests for means of continuous variables, Wilcoxon 2-sample test for medians of continuous variables, and Chi-square tests for categorical variables.

Table II. Geometric mean serum concentrations (lipid adjusted), 95% confidence intervals, and p-values of selected persistent pesticides, polychlorinated biphenyls (PCB), and polybrominated diphenyl ethers (PBDE), and urinary concentrations (µg/g creatinine) of phthalate metabolites in a population of Alaska Native women: 1999–2002

	Geometric mean (ng/g lipid) (95% confidence interval)
Analyte	Total (N=170)	Case (N=75)	Control (N=95)	p
Persistent pesticides (ng/g lipid)
p,p′-Dichlorodiphenylethylene (DDE)	3,912 (3,372–4,539)	3,866 (3,103–4,866)	3,944 (3,229–4,817)	0.91
Hexachlorobenzene	404 (340–480)	340 (270–433)	464 (365–590)	0.08
Mirex	39.9 (33.3–47.8)	33.1 (25.8–42.5)	45.6 (35.5–59.2)	0.08
Oxychlordane	241 (200–290)	215 (166–276)	265 (200–347)	0.28
β-Hexachlorocyclohexane	151 (126–180)	143 (110–183)	158 (123–202)	0.57
γ-Hexachlorocyclohexane	8.02 (7.60–8.47)	8.33 (7.77–8.94)	7.77 (5.99–8.50)	0.23
o,p′-Dichlorodiphenyltrichloroethane (DDT)	15.6 (14.1–17.3)	15.0 (13.1–17.3)	16.1 (13.9–18.7)	0.51
p,p′-DDT	62.8 (55.0–71.8)	56.3 (46.5–68.0)	68.7 (56.8–82.3)	0.16
trans-Nonachlor	344 (282–420)	302 (226–403)	380 (290–503)	0.27
Polychlorinated biphenyls (ng/g lipid)
138/158	413 (347–491)	386 (304–490)	436 (340–558)	0.50
153	590 (494–705)	541 (424–689)	632 (491–815)	0.39
180	345 (297–401)	325 (266–398)	362 (291–450)	0.49
Polybrominated diphenyl ether (ng/g lipid)
47	30.4 (24.9–37.2)	38.8 (28.6–52.7)	25.1 (19.3–32.7)	0.04
Phthalate metabolites (µg/g creatinine)
Mono-butyl phthalate (MBP)	15.9 (13.3–19.1)	14.6 (10.7–19.8)	17.1 (13.8–21.2)	0.41
Mono-benzyl phthalate (MBzP)	7.1 (6.1–8.4)	7.6 (5.8–10.0)	6.7 (5.6–8.2)	0.46
Mono-(2-ethyl-5-hydroxyhexyl) phthalate (MEHHP)	32.8 (27.7–38.9)	36.4 (27.6–48.0)	30.1 (24.4–37.2)	0.28
Mono-(2-ethylhexyl) phthalate (MEHP)	4.2 (3.3–5.4)	5.3 (3.6–7.7)	3.5 (2.6–4.7)	0.10
Mono-(2-ethyl-5-oxohexyl) phthalate (MEOHP)	21.9 (18.7–25.7)	24.3 (18.8–31.5)	20.1 (16.4–24.5)	0.24
Mono-ethyl phthalate (MEP)	57.4 (45.8–71.9)	50.5 (36.4–70.0)	63.8 (46.8–87.0)	0.31
Mono-methyl phthalate (MMP)	1.7 (1.4–2.1)	1.7 (1.3–2.3)	1.7 (1.4–2.2)	0.98

Table III. Univariate and multivariable odds ratios (OR), 95% confidence intervals, and p-values for the association between breast cancer and selected persistent pesticides, polychlorinated biphenyls (PCB), polybrominated diphenyl ethers (PBDE), and phthalate metabolites among Alaska Native women – 1999–2002

Analyte	Univariate OR (95% confidence interval) p-value	Multivariable OR (95% confidence interval) p-value
Persistent pesticides
p,p′-Dichlorodiphenylethylene (DDE)	1.05 (0.57–1.92) 0.88	0.60 (0.26–1.43) 0.25
Hexachlorobenzene	0.78 (0.43–1.44) 0.44	0.47 (0.19–1.16) 0.10
Mirex	0.82 (0.45–1.50) 0.55	0.65 (0.28–1.55) 0.33
Oxychlordane	1.05 (0.57–1.92) 0.88	0.91 (0.35–2.35) 0.84
β-Hexachlorocyclohexane	1.19 (0.65–2.18) 0.58	1.21 (0.44–3.31) 0.71
γ-Hexachlorocyclohexane	1.70 (0.92–3.12) 0.09	1.88 (0.88–4.03) 0.10
o,p′-Dichlorodiphenyltrichloroethane (DDT)	0.99 (0.54–1.82) 0.99	1.00 (0.48–2.11) 1.00
p,p′-DDT	0.55 (0.30–1.01) 0.05	0.49 (0.22–1.10) 0.08
trans-Nonachlor	0.98 (0.53–1.80) 0.95	0.65 (0.26–1.66) 0.37
Polychlorinated biphenyls
138/158	0.95 (0.52–1.75) 0.88	0.64 (0.27–1.52) 0.31
153	0.95 (0.52–1.75) 0.88	0.55 (0.22–1.41) 0.21
180	0.87 (0.47–1.59) 0.64	0.43 (0.17–1.09) 0.08
Polybrominated diphenyl ether
47	1.79 (0.97–3.32) 0.06	1.58 (0.75–3.33) 0.23
Phthalate metabolites
Mono-butyl phthalate (MBP)	0.78 (0.43–1.45) 0.44	0.66 (0.32–1.39) 0.28
Mono-benzyl phthalate (MBzP)	1.22 (0.66–2.25) 0.52	1.53 (0.73–3.22) 0.26
Mono-(2-ethyl-5-hydroxyhexyl) phthalate (MEHHP)	1.28 (0.69–2.35) 0.44	1.50 (0.71–3.17) 0.28
Mono-(2-ethylhexyl) phthalate (MEHP)	2.16 (1.16–4.05) 0.02	2.43 (1.12–5.24) 0.02
Mono-(2-ethyl-5-oxohexyl) phthalate (MEOHP)	0.95 (0.52–1.76) 0.88	1.15 (0.54–2.44) 0.71
Mono-ethyl phthalate (MEP)	0.71 (0.39–1.31) 0.28	0.55 (0.26–1.18) 0.13
Mono-methyl phthalate (MMP)	0.95 (0.52–1.76) 0.88	0.86 (0.40–1.85) 0.70

Table IV. Geometric mean serum concentrations (ng/g lipid) of selected persistent pesticides, polychlorinated biphenyls (PCB), and polybrominated diphenyl ethers (PBDE), and urinary concentrations (µg/g creatinine) of phthalate metabolites in a population of Alaska Native women with specific tumour hormone receptor status – 1999–2002

	Geometric mean (95% confidence interval)
	ER+/PR+ cases (n=40)	ER–/PR– cases (n=13)	p
Persistent pesticides
p,p′-Dichlorodiphenylethylene (DDE)	3,103 (2,231–4,316)	4,273 (2,566–7,115)	0.31
Hexachlorobenzene	290 (200–420)	441 (240–804)	0.25
Mirex	26.8 (18.7–38.5)	40.9 (18.2–91.8)	0.27
Oxychlordane	166 (113–242)	273 (134–556)	0.19
β-Hexachlorocyclohexane	110 (74–162)	185 (103–334)	0.16
γ-Hexachlorocyclohexane	7.92 (7.24–8.76)	8.58 (6.69–11.02)	0.49
o,p′-Dichlorodiphenyltrichloroethane (DDT)	13.9 (11.3–17.1)	17.0 (11.7–24.5)	0.35
p,p′-DDT	49.4 (37.0–66.7)	66.0 (40.9–108)	0.32
trans-Nonachlor	217 (141–337)	416 (192–907)	0.13
Polychlorinated biphenyls
138/158	327 (237–455)	503 (270–925)	0.19
153	424 (296–614)	672 (340–1326)	0.22
180	273 (202–372)	354 (198–626)	0.41
Polybrominated diphenyl ethers
47	34.1 (21.3–54.1)	51.9 (23.1–116.8)	0.36
Phthalate metabolites
Mono-butyl phthalate (MBP)	15.3 (9.0–26.1)	12.8 (6.7–24.8)	0.71
Mono-benzyl phthalate (MBzP)	8.3 (5.4–12.8)	6.2 (3.1–12.7)	0.51
Mono-(2-ethyl-5-hydroxyhexyl) phthalate (MEHHP)	35.5 (24.5–51.4)	49.4 (20.7–119.1)	0.40
Mono-(2-ethylhexyl) phthalate (MEHP)	4.6 (2.8–7.6)	11.1 (3.7–33.8)	0.10
Mono-(2-ethyl-5-oxohexyl) phthalate (MEOHP)	23.3 (16.8–32.5)	36.6 (16.1–83.9)	0.21
Mono-ethyl phthalate (MEP)	49.6 (32.3–76.1)	47.7 (23.0–98.9)	0.93
Mono-methyl phthalate (MMP)	1.54 (1.1–2.2)	1.48 (0.5–4.4)	0.95