Endocrine disrupting chemicals and breast cancer: a systematic review of epidemiological studies

Figures & data

Figure 1. PRISMA flow diagram.

Table 1. Summary of papers for DDT or its metabolites exposure and breast cancer risk.

Study/Country	Study year	Study design	Cases	Controls (or cohorts)	Biological specimen(s)	Biomarker(s)	Breast cancer risk	Reference
Wolff/ US	1985-1991	Case-control	58	171	Serum	p, p’-DDE	↑	WWolff et al. (1993)
López-Carrillo/ Mexico	1994-1996	Hospital based case-control	141	141	Serum	p, p’-DDE p, p’-DDT	No association	(López-Carrillo et al. 1997)
Hunter/ US	1989-1990, 1992	Case-control	236	236	Plasma	p, p’-DDE	No association	(Hunter et al. 1997)
Moysich/ US	1986-1991	Case-control	154	192	Serum	p, p’-DDE	No association	(Moysich et al. 1998)
Stellman/ US	1994-1996	Hospital based case-control	362	293	Serum, adipose tissue	p, p’-DDE o, p’-DDD p, p’-DDT	↑	(Stellman et al. 1998)
Høyer/ US	1996-1997	Case-control	240	447	Serum	p, p’-DDE p, p’-DDT	No association	(Høyer et al. 1998)
Helzlsouer/ US	1974-1989	Nested case-control	235, 105	235, 105	Serum	p, p’-DDE p, p’-DDT	No association	(Helzlsouer et al. 1999)
Dorgan/ US	1977-1987	Case-control	105	208	Serum	o, p’-DDE p, p’-DDE p, p’-DDD o, p’-DDT, p, p’-DDT	No association	(Dorgan et al. 1999)
Mendonça/ Brazil	1995-1996	Hospital based case-control	177	350	Serum	p, p’-DDE	No association	(Mendonça et al. 1999)
Aronson/ Canada	1995-1997	Hospital based case-control	217	213	Adipose tissue	p, p’-DDE p, p’-DDT	No association	(Aronson et al. 2000)
Zheng/ US	1995-1997	Case-control	475	502	Serum	p, p’-DDE	No association	(Zheng, Holford, Tessari, et al. 2000)
Høyer/ Denmark	1976-1978, 1981-1983	Cohort nested case control	155	274	Serum	p, p’-DDT	↑	(Høyer, Jørgensen, Brock, et al. 2000)
Bagga/ US	1995-1996	Case-control	73	73	Adipose tissue	p, p’-DDE p, p’-DDD p, p’-DDT	No association	(Bagga et al. 2000)
Wolff/ US	1987-1992, 1994	Case-control	148	295	Serum	p, p’-DDE	No association	(Wolff, Zeleniuch-Jacquotte, et al. 2000)
Wolff/ US	N.A.	Hospital based case-control	175	355	Serum	p, p’-DDE p, p’-DDT	No association	(Wolff, Zeleniuch-Jacquotte, et al. 2000)
Millikan/ US	1993-1996	Population based case-control	748	659	Plasma	p, p’-DDE	↑	(Millikan et al. 2000)
Stellman/ US	1994-1996	Hospital based case-control	232	323	Adipose tissue	p, p’-DDE	No association	(Stellman et al. 2000)
Elizabeth/ Norway	1973-1991	Nested case-control	150	150	Serum	p, p’-DDE p, p’-DDT	No association	(Ward et al. 2000)
Laden/ US	1976, 1989-1990, 1994	Follow up of prospective cohort study	372	372	Plasma	p, p’-DDE	No association	(Laden, Collman, et al. 2001)
Woolcott/ Canada	1995-1997	Hospital based case-control	217	213	Adipose tissue	p, p’-DDE p, p’-DDT	No association	(Woolcott et al. 2001)
Ahmed/ Egypt	1999-2000	Case-control	64	11	Serum	p, p’-DDE	↑	(Ahmed, Loutfy, and Shiekh 2002)
Gammon/ US	1886-1997	Population based case-control	646	429	Serum	p, p’-DDE	No association	(Gammon et al. 2002)
Mathur/ India	N.A.	Case-control	135	50	Blood	p, p’-DDE p, p’-DDD p, p’-DDT	↑	(Mathur et al. 2002)
Charlier/ Belgium	1999-2000	Case-control	159	250	Serum	Total DDT	↑	(Charlier et al. 2003)
Pavuk/ Slovakia	1997-1999	Case-control	24	88	Serum	p, p’-DDE p, p’-DDT	↑ for DDE	(Pavuk et al. 2003)
Mucat/ US	1994-1996	Case-control	224	359	Adipose tissue	p, p’-DDE p, p’-DDT o, p’-DDD	No association	(Muscat et al. 2003)
McElroy/ US	1997-2001	Population based case-control study	1481	1301	N.A.	DDT	No association	(McElroy et al. 2004)
Charlier/ Belgium	2001-2002	Case-control	231	290	Serum	p, p’-DDE o, p’-DDT p, p’-DDT	↑ for DDE	(Charlier, Albert, et al. 2004)
Raaschou-Nielsen/ Denmark	1993-1997	Nested case-control	409	409	Adipose tissue	p, p’-DDE p, p’-DDT	No association	(Raaschou-Nielsen et al. 2005)
Li/ China	2003-2004	Case-control	104	154	Serum	p, p’-DDE p, p’-DDT	↑ for DTT among premenopausal women with CYP1A1 m2 variant genotype	(Li et al. 2006)
Gatto/ US	1995-1998	Multi-center population-based case-control study	355	327	Serum	p, p’-DDE	No association	(Gatto et al. 2007)
Cohn/ US	1959-1967	Prospective nested case-control	129	129	Serum	p, p’-DDT	↑	(Cohn et al. 2007)
Iwasaki/ Japan	1990-1995, 2002	Nested case-control	139	139 (24,226)	Plasma	p, p’-DDE p, p’-DDT	No association	(Iwasaki et al. 2008)
Itoh/ Japan	2001-2005	Matched case-control	403	403	Serum	p, p’-DDE o, p’-DDT p, p’-DDT	No association	(Itoh et al. 2009)
Chang/ China	2006-2007	Case-control	70	30	Serum	p, p’-DDT	N.A.	(Chang et al. 2008)
White/ US	1996-1997	Case-control	1,508	1,556	Serum	p, p’-DDE p, p’-DDT	↑	(White et al. 2013)
Tang/ China	2005-2007	Case-control	78	72	Serum	p,p′-DDT p,p′-DDE p,p′-DDD o,p′-DDT o,p′-DDE o,p′-DDD	↑	(Tang et al. 2014)
Holmes/ US	1999-2002	Case-control	75	95	Serum	p, p’-DDE o, p’-DDT p, p’-DDT	No association	(Holmes et al. 2014)
Cohn/ US	N.A.	Case-control	118	354 (9,300)	Serum	p, p’-DDE o, p’-DDT p, p’-DDT	↑ for o, p’-DDT	(Cohn et al. 2015)
Parada/ US	1996-1997, 2011	Population based case-control	224	409	Blood	p, p’-DDE p, p’-DDT	↑	(Parada Jr. et al. 2016)
He/ China	2015-2016	Hospital based case control	56	46	Adipose tissue	p, p’-DDE	↑	(He et al. 2017)
Louis/ US	1993-1997, 2012-2013	Prospective cohort	N.A.	28,909 (2,191 exposed)	N.A.	p, p’-DDT	No association	(Louis et al. 2017)
Cohn/ US	1959-1967, 2010	Prospective, nested case-control	153	432	Serum	p, p’-DDT	↑	(Cohn, Cirillo, and Terry 2019)
Huang/ China	2014-2016	Hospital-based case-control	209	165	Adipose tissue	p, p’-DDE p, p’-DDT	↑	(Huang et al. 2019)
Kaur/ India	2015-2016	Hospital-based case-control	42	42	Serum	p, p’-DDE p, p’-DDT	↑ for DDE	(Kaur et al. 2019)
Paydar/ Iran	2015-2016	Case-control	58	27	Serum	p, p’-DDE p, p’-DDT	↑	(Paydar et al. 2019)
Parada/ US	1993-1996	Population based case-control	748	N.A.	Plasma	p, p’-DDE p, p’-DDT	↑	(Parada et al. 2019)

Table 2. Summary of papers for TCDD or dioxin exposure and breast cancer risk.

Study/Country	Study year	Study design	Cases	Controls (or cohorts)	Biological specimen	Biomarker(s)	Breast cancer risk	Reference
Warner/ Italy	1996	Retrospective cohort	N.A.	981	Serum	TCCD	↑	(Warner et al. 2002)
Warner/ Italy	1996	Follow-up	N.A.	981	Serum	TCCD	↑	(Warner et al. 2011)
Danjou/ France	1990-2008	Prospective cohort, Nested case-control	419	716	N.A.	N.A.	No association	(Danjou et al. 2019)
VoPham/ US	1989-2013	Prospective cohort	N.A.	3,840	N.A.	N.A.	No association	(VoPham et al. 2020)

Table 3. Summary of papers for BPA exposure and breast cancer risk.

Study/Country	Study year	Study design	Cases	Controls (or cohorts)	Biological specimen	Biomarker(s)	Breast cancer risk	Reference
Trabert/ Poland	2000-2003	Population-based case-control	575	575	Urine	BPA-G	No association	(Trabert et al. 2014)
Morgan/ US	1999-2004	Cross-sectional	31	115	Serum	BPA	No association	(Morgan et al. 2017)

Table 4. Summary of papers for phthalates or its metabolites exposure and breast cancer risk.

Study/Country	Study year	Study design	Cases	Controls (or cohorts)	Biological specimen	Biomarker(s)	Breast cancer risk	Reference
Reeves/US	1993-1998	Nested case-control	419	838	Urine	13 Phthalates	No association	(Reeves et al. 2019)
Parada/US	1997-1998	Case-control	710	598	Urine	11 Phthalates metabolites	↑ for MCPP, MCNP, MCOP	(Parada et al. 2018)
Holmes/US	1999-2002	Case-control	75	95	Urine	10 Phthalates metabolites	↑ for MEHP, DEHP	(Holmes et al. 2014)
Morgan/US	2003-2004 2005-2006, 2007-2008, 2009-2010	Cross-sectional survey	43	1,964	Urine	13 Phthalates metabolites for 2003-2004, 15 Phthalates metabolites for 2005-2006, 2007-2008, 2009-2010	No association	(Morgan et al. 2017)
Lizbeth López-Carrillo, Merida-Ortega/Northern Mexico	2007-2008	Population-based case control	233	221	Urine	10 Phthalates metabolites	↑ for López-Carrillo et al. 2010 study; ↑ when interact with dietary flavonoids for Merida-Ortega 2016 study	(López-Carrillo et al. 2010; Mérida-Ortega et al. 2016)

Table 5. Summary of papers for PFOA exposure and breast cancer risk.

Study/Country	Study year	Study design	Cases	Controls (or cohorts)	Biological specimen	Biomarker(s)	Breast cancer risk	Reference
Bonefeld-Jørgensen/ Greenland	2000-2003	Case-control	31	115	Serum	PFOA	↑	(Bonefeld-Jørgensen et al. 2011)
Bonefeld-Jørgensen/ Denmark	1996-2002, 2010	Case-control	250	233	Serum	PFOA	No association	(Bonefeld-Jørgensen et al. 2014)
Wielsøe/ Greenland	2000-2003, 2011-2014	Case-control	3,166	11,562	Serum	PFOA	↑	(Wielsøe, Kern, and Bonefeld-Jørgensen 2017)
Hurley/ US	2011-2015	Nested case-control	902	858	Serum	PFOA	No association	(Hurley et al. 2018)
Mancini/ France	1925-1950, 1990	Nested case-control	194	194	Serum	PFOA	↑	(Mancini et al. 2020)

Table 6. Summary of papers for PCBs exposure and breast cancer risk.

Study/Country	Study year	Study design	Cases	Controls (or cohorts)	Biological specimen(s)	Biomarker(s)	Breast cancer risk	Reference
Hunter/ US	1989-1990, 1992	Case-control	230	230	Plasma	Total PCBs	No association	(Hunter et al. 1997)
Moysich/ US	1986-1991	Case-control	154	192	Serum	73 PCB congeners	No association	(Moysich et al. 1998)
Høyer/ US	1996-1997	Case-control	240	477	Serum	28 PCB congeners	No association	(Høyer et al. 1998)
Stellman/ US	1994-1996	Hospital-based case-control	362	293	Adipose tissue, serum	14 PCB congeners	No association	(Stellman et al. 1998)
Dorgan/ US	1977-1987	Case-control	105	208	Serum	27 PCB congeners	No association	(Dorgan et al. 1999)
Helzlsouer/ US	1974, 1989	Nested case-control	235	105	Serum	26 PCB congeners	No association	(Helzlsouer et al. 1999)
Laden/ US	1989-1990, 1992	Nested case-control	240	240	Plasma	16 PCB congeners	Not mentioned	(Laden et al. 1999)
Moysich/ US	1989-1991	Case-control	154	192	Serum	56 PCB congeners	CYP1A1 isoleucine-to-valine substitution may be a risk factor for breast cancer among women with elevated PCB body burden.	(Moysich et al. 1999)
Aronson/ Canada	N.A.	Hospital-based case-control	217	213	Biopsy tissue	14 PCB congeners	↑	(Aronson et al. 2000)
Hoyer/ Denmark	1976-1978, 1981-1983	Nested case-control	155	274	Serum	PCB 118, PCB 138, PCB 153, PCB 180	↑ for PCB118 and PCB138	(Høyer, Jørgensen, Brock, et al. 2000)
Millikan/US	1993-1996	Population-based case-control	748	659	Plasma	35 PCB congeners	↑ for total PCB	(Millikan et al. 2000)
Stellman/ US	1994-1996	Hospital-based case-control	232	323	Adipose tissue	14 PCB congeners	↑ for PCB183	(Stellman et al. 2000)
Ward/ Norway	19973-1991	Nested case-control	150	150	Serum	26 PCB congeners	No association	(Ward et al. 2000)
Wolff/ US	1987-1992, 1994	Prospective cohort, case-control	148	295 (14,275)	Blood	29 PCB congeners	No association	(Wolff, Zeleniuch-Jacquotte, et al. 2000)
Zheng/ US	1995-1997	Case-control	475	502	Serum	9 PCB congeners	No association	(Zheng, Holford, Tessari, et al. 2000)
Zheng/ US	1994-1997	Case-control	304	186	Adipose tissue	9 PCB congeners	No association	(Zheng, Holford, Tessari, et al. 2000)
Hoyer/ Denmark	1976-78, until 1993	Nested case-control	268	536	Serum	28 PCB congeners	No association	(Høyer et al. 2001)
Laden/ US	1976, 1989-1990, follow up through 1994	Nested case-control	370	370	Plasma	PCB 118, PCB 138, PCB 153, PCB 180	No association	(Laden, Collman, et al. 2001)
Woolcott/ Canada	1995-1997	Case-control	217	213	Adipose tissue	14 PCB congeners	↑ and PCBs were associated with poor prognosis	(Woolcott et al. 2001)
Ahmed/ Egypt	1999-2000	Cohort	64	11	Serum	Not specified	No association	(Ahmed, Loutfy, and Shiekh 2002)
Demers/ Canada	1994-1997	Case-control	314	523	Plasma lipid	14 PCB congeners	↑ for dioxin-like PCBs	(Demers et al. 2002)
Gammon/ US	1996-1997	Case-control	646	429	Serum	24 PCB congeners	No association	(Gammon et al. 2002)
Laden/ US	1976, 1989-1990 (blood), follow up through 1994	Nested case-control	367	367	Plasma	21 PCB congeners	↑ for women who have the variant CYP1A1-exon7polymorphism.	(Laden et al. 2002)
Lopez-Carrillo/ Mexico	1994-1996	Case-control	95	95	Serum	Not specified	No association	(López-Carrillo et al. 2002)
Muscat/ US	1994-1996	Case-control	224	N.A.	Adipose tissue	14 PCB congeners	↑ recurrence	(Muscat et al. 2003)
Pavuk/ Slovakia	1997-1999	Case-control	24	88	Serum	15 PCB congeners	↓ but not statistically significant	(Pavuk et al. 2003)
Charlier/ Belgium	N.A.	Case-control	60	60	Serum	7 PCB congeners	↑ for PCB153	(Charlier, Albert, et al. 2004)
Li/ US	1993-1996, 1996-2001	Population-based case-control	612	599	Serum	35 PCB congeners	↑ for CYP1A1 M2 and M3-containing genotypes and high levels of PCB exposure	(Li et al. 2004)
McElroy/ Belgium	1997-2001	Population-based case-control	1,481	1,301	N.A.	N.A.	No association	(McElroy et al. 2004)
Rusiecki/ US	1994-1997	Hospital-based case-control	266	347	Adipose tissue, serum	9 PCB congeners	No association	(Rusiecki et al. 2004)
Zhang/ US	1999-2002	Case-control	374	406	Serum	9 PCB congeners	↑ for CYP1A1 M2 and PCB exposure	(Zhang et al. 2004)
Raaschou-Nielsen/ Denmark	1993-1997	Nested case-control	409	409	Adipose tissue	18 PCB congeners	No association	(Raaschou-Nielsen et al. 2005)
Prince/ US	Updated through 1998	Cohort	N.A.	2,572	N.A.	N.A.	No association	(Prince et al. 2006)
Gatto/ US	1995-1998	Multi-center population-based case-control	355	327	Serum	N.A.	No association	(Gatto et al. 2007)
Silver/ US	1970-1999	Occupation cohort	281	5,471	N.A.	N.A.	No association	(Silver et al. 2008)
Itoh/ Japan	2001-2005	Matched case-control	403	403	Serum	More than 41 PCB congeners	No association	(Itoh et al. 2009)
Villeneuve/ France, Denmark	1995-1997	Case-control	104	1,901	N.A.	N.A.	↑	(Villeneuve et al. 2010)
Bonefeld-Jorgensen/ Greenland	2000-2003	Case-control	31	115	Serum	12 PCB congeners	↑ for high PCB exposure (PCBs > 2645 ug/kg lipid)	Bonefeld-Jørgensen et al. 2011)
Recio-Vega/ Mexico	N.A.	Case-control	70	70	Serum	20 PCB congeners	↑	( Recio‐Vega et al. 2011)
Cohn/ US	1959-1967	Nested case-control	112	112	Serum	16 PCB congeners	↑ for PCB203 ↓ for PCB167 and PCB187	(Cohn et al. 2012)
Arrebola/ Spain	2003-2004	Cohort	N.A.	368	Adipose tissue	PCB 138, PCB 153, PCB 180	No association	(Arrebola et al. 2015)
Ruder/ US	1957-1977, 1939-1976, 1946-1977, 2008	Cohort	N.A.	24,865	N.A.	N.A.	No association	(Ruder et al. 2014)
Arrebola/ Spain	2012-2014	Cohort	103	N.A.	Adipose tissue, serum	PCB 138, PCB 153, PCB 180	PCB associated with breast cancer aggressiveness	(Arrebola et al. 2016)
Donat-Vargas/ Sweden	1997 (14 years follow-up)	Population-based prospective cohort	1,593	35,184	N.A.	N.A.	No association	(Donat-Vargas et al. 2016)
He/ China	2014-2015	Cohort	N.A.	223	Adipose tissue	7 PCB congeners	↑	(He et al. 2017)
Morgan/ US	1999-2004	Cohort	43	1,964	Serum	6 PCB congeners	↑ for PCB138	(Morgan et al. 2017)
Ruder/ US	1957-1977, 1939-1976, 1946-1977, 2008	Cohort	N.A.	24,865	N.A.	N.A.	No association	(Ruder et al. 2017)
Wielsøe/ Greenland	2000-2003, 2011-2014	Case-control	7	84	Serum	14 PCB congeners	↑	(Wielsøe, Kern, and Bonefeld-Jørgensen 2017)
Huang/ China	2014-2016	Hospital-based case-control	209	165	Adipose tissue	7 PCB congeners	↑ for PCB118, PCB138, PCB153, and PCB180 ↓ for PCB28, PCB52 and PCB101	(Huang et al. 2019)
Rusiecki/ US	1998	Cohort	N.A.	210	Serum	27 PCB congeners	↑	(Rusiecki et al. 2020)

Table 7. Summary of papers for PBDEs exposure and breast cancer risk.

Study/Country	Study year	Study design	Cases	Controls (or cohorts)	Biological specimen	Biomarker(s)	Breast cancer risk	Reference
Holmes/ US	1999-2002	Case-control	75	95	Urine	8 PBDE congeners	↑ for BDE-47	(Holmes et al. 2014)
Hurley/ US	2006-2014	Nested case-control	902	936	Serum	19 PBDE congeners	No association	(Hurley et al. 2019)
Hurley/ US	2006-2014	Case-control	78	56	Adipose tissues	5 PBDE congeners	No association	(Hurley et al. 2011)
Mancini/ France	1994-1999, identified up to 2013	Nested case-control	197	197	Plasma	6 PBDE congeners	No association	(Mancini et al. 2020)
McElroy/ US	1996-2000	Case-control	3,753	5,155	N.A.	N.A.	No association	(McElroy et al. 2004)
He/ China	2014-2016	Case-control	209	165	Adipose tissues	14 PBDE congeners	↑	(He et al. 2018)
Kachuri/ Canada	2012-2015	Case-control	305	144	Serum	8 PBDE congeners	↑	(Kachuri et al. 2018)

Table 8. Summary of papers for oral contraceptive pills exposure and breast cancer risk.

Study/Country	Study year	Study design	Cases	Controls (or cohorts)	Biological specimen	Breast cancer risk	Reference
Kumle/ Norway, Sweden	1991-1999	Prospective cohort	1,008	106,844	N.A.	↑	(Kumle et al. 2002)
Rosenberg/ US	1976-1996, 1993-2007	Case control	907	1,711	N.A.	↑	(Rosenberg et al. 2009)
Urban/ South Afirca	1995-2006	Hospital-based prospective case control	1,664	1,492	N.A.	↑ with use but no association with duration of use	(Urban et al. 2012)
Bethea/ US	1995-2011, 1993-2001, 2003	Prospective cohort; Population-based case control; Population-based case control	N.A.; 1,424; 370	59,000; 2,020; 207	N.A.	↑ with dosage, recency and duration of use	(Bethea et al. 2015)
Nur/ Sweden	1993-2012	Population-based prospective cohort	2,120	N.A.	N.A.	No association with breast cancer-related mortality	(Nur et al. 2019)
Mørch/ Denmark	1995-2012	Prospective cohort	N.A.	1,797,932	N.A.	↑	(Mørch et al. 2017)
Wahidin/ Indoesia	2013	Hospital-based case control	381	381	N.A.	↑ with use and duration of use	(Wahidin, Djuwita, and Adisasmita 2018)
Bardaweel/ Jordan	2017	Case control	225	225	N.A.	↑	(Bardaweel et al. 2019)

Table 9. Summary of papers for genistein exposure and breast cancer risk.

Study/ Country	Study year	Study design	Cases	Controls (or cohorts)	Biological specimen	Biomarker(s)	Breast cancer risk	Reference
Ingram/ Australia	1992-1994	Case-control	144	144	Urine	Genistein	No association	(Ingram et al. 1997)
Murkies/ Australia	1997-1998	Case-control	25	155	Urine	Genistein	↓	(Murkies et al. 2000)
Dai/ China	1996-1998	Population-based case control	1,459	1,556	N.A.	N.A.	↓	(Dai et al. 2001)
Horn-Ross/ US	1995-1998	Population-based case-control	1,326	1,657	N.A.	N.A.	No association	(Horn-Ross et al. 2001)
Tonkelaar/ Netherlands	1974-1984, 1977-1985	Nested case-control	88	268	Urine	Genistein	No association	(Tonkelaar et al. 2001)
Peterson/ Greece	1989-1991	Case-control	820	1,548	N.A.	N.A.	No association	(Peterson et al. 2003)
Yamamoto/ Japan	1990-1999	Population-based prospective cohort	179	21,852	N.A.	N.A.	↓	(Yamamoto et al. 2003)
Keinan-Boker/ Netherlands	1993-1997	Population-based prospective cohort	280	15.555	N.A.	N.A.	No association	(Keinan-Boker et al. 2004)
Sartippour/ US	1999-2001	Pilot	17	N.A.	Serum	Genistein	No association	(Sartippour et al. 2004)
Silvia/ United Kingdom	1995-1999	Population-based case-control	240	477	N.A.	N.A.	↓	(Silva et al. 2004)
Wu/ US	1995-1998	Population-based case-control	97	97	Plasma	Genistein	↓	(Wu et al. 2004)
Bosetti/ Italy	1991-1994	Case-control	2,569	2,588	N.A.	N.A.	↓	(Bosetti et al. 2005)
Hirose/ Japan	1988-2002	Population-based case-control	167	854	N.A.	N.A.	↓ for premenopausal women	(Hirose et al. 2005)
Lee/ Taiwan	1996-1999	Population-based case-control	250	219	N.A.	N.A.	↓ for older subjects (>40), but not for younger subjects (<40)	(Lee et al. 2005)
Shannon/ China	1989-1991, 1995-2000	Population-based case-control	378	1,070	N.A.	N.A.	No association	(Shannon et al. 2005)
Ho/ Hong Kong	1998	Population-based case-control	174	10,968	N.A.	N.A.	↓	(Ho et al. 2006)
Thanos/ Canada	2002-2003	Population-based case-control	3,024	3,420	N.A.	N.A.	↓	(Thanos et al. 2006)
Touillaud/ France	1990-1991, 1993-1995	Population-based prospective cohort	402	117,652	N.A.	N.A.	No association	(Touillaud et al. 2006)
Do/ Korea	1999-2003	Population-based case-control	359	708	N.A.	N.A.	↓	(Do et al. 2007)
Fink/ US	1996-1997	Population-based case-control	1,434	1,440	N.A.	N.A.	↓ for postmenopausal breast cancer	(Fink et al. 2007)
Nishio/ Japan	1988-1990	Population-based prospective cohort	N.A.	30,454	N.A.	N.A.	No association	(Nishio et al. 2007)
Verheus/ Netherlands	2003	Nested case-control	383	383	Plasma	Genistein	↓	(Verheus et al. 2007)
Ward/ United Kingdom	1993-1997, 1993-2006	Population-based prospective cohort	237	952	Serum, urine	Genistein	No association	(Ward et al. 2008)
Wu/ Singapore	1993-2005	Population-based prospective cohort	629	35,303	N.A.	N.A.	↓	(Wu et al. 2008)
Guha/ US	1997-2000, 2000-2002	Prospective cohort	N.A.	1,954	N.A.	N.A.	↓ breast cancer recurrence	(Guha et al. 2009)
Iwasaki/ Japan and Brazil	2001-2005, 2001-2006	Hospital-based case-control	850	850	N.A.	N.A.	↓ for Japanese Brazilians, non-Japanese Brazilians, and premenopausal Japanese; ↓ for all three populations combined	(Iwasaki et al. 2009)
Toi/ Japan	2007-2009	Population-based case-control	306	662	N.A.	N.A.	↓	(Toi et al. 2013)
Wada/ Japan	1992-2008	Population-based prospective cohort	172	15,607	N.A.	N.A.	↓ for postmenopausal breast cancer, but no association for premenopausal breast cancer	(Wada et al. 2013)
Wei/ China	2004-2008	Prospective cohort	N.A.	300,852	N.A.	N.A.	No association	(Wei et al. 2019)

Table 10. Summary of papers for mycoestrogen exposure and breast cancer risk.

Study/Country	Study year	Study design	Cases	Controls (or cohorts)	Exposure	Biological specimen	Biomarker(s)	Breast cancer risk	References
Pillay/ South Africa	N.A.	Case-control	28	24	Dietary	Serum	ZEA, α-ZOL, β-ZOL	No association	(Pillay et al. 2002)
Belhassen/ Tunisia	2012	Case-control	69	41	N.A.	Urine	ZEA, α-ZOL, β-ZOL, α-ZAL, β-ZAL, ZAN	↑ for α-ZAL; no association for ZON and other metabolites	(Belhassen et al. 2015)

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