World J Oncol

World Journal of Oncology, ISSN 1920-4531 print, 1920-454X online, Open Access

Article copyright, the authors; Journal compilation copyright, World J Oncol and Elmer Press Inc

Journal website https://wjon.elmerpub.com

Original Article

Volume 17, Number 5, October 2026, pages 725-738

Association Between Sleep Disorders and Breast Cancer: An Analysis Based on NHANES and Mendelian Randomization

↓ Figure 2. Forest plot of subgroup analysis. BMI: body mass index; OR: odds ratio; 95% CI: 95% confidence interval.

↓ Figure 3. Scatter plot of sleep disorders and ER− breast cancer. The slope of each line denotes the estimated effect of per Mendelian randomization method. ER−: estrogen receptor-negative; MR: Mendelian randomization; SNP: single nucleotide polymorphism.

↓ Figure 4. Forest plot of sleep disorder-related SNPs associated with ER− breast cancer. The red points demonstrate the integrated estimates using all SNPs together, using IVW method. Horizontal lines represent 95% confidence intervals. ER−: estrogen receptor-negative; IVW: inverse variance weighted; MR: Mendelian randomization; SNP: single nucleotide polymorphism.

↓ Figure 5. Leave-one-out analysis of the causal association of sleep disorders and ER− breast cancer. Black points depict the IVW method was used to assess the causal effect, excluding single specific variant from the analysis. The red point denotes the inverse-variance weighted estimate using all SNPs. ER−: estrogen receptor-negative; IVW: inverse variance weighted; MR: Mendelian randomization.

↓ Figure 6. Funnel plot. Vertical lines represent estimates with all SNPs. Symmetry in the funnel plot demonstrates no obvious horizontal pleiotropy. MR: Mendelian randomization; SNP: single nucleotide polymorphism.

↓ **Table 1.** Comparison of Baseline Characteristics in Groups With and Without Breast Cancer
Variable	Group	Overall	Breast cancer	No cancer	P-value
BMI: body mass index; SD: standard deviation.
N		8,366	290	8,076
Gender (%)	Female	8,366 (100.0)	290 (100.0)	8,076 (100.0)
Age (mean (SD))		50.97 (17.66)	67.69 (10.81)	50.37 (17.56)	< 0.001
Race (%)					< 0.001
	Mexican American	1,439 (17.2)	33 (11.4)	1,406 (17.4)
	Non-Hispanic Black	2,002 (23.9)	51 (17.6)	1,951 (24.2)
	Non-Hispanic White	2,633 (31.5)	150 (51.7)	2,483 (30.7)
	Other Hispanic	1,053 (12.6)	26 (9.0)	1,027 (12.7)
	Other Race including multi-racial	1,239 (14.8)	30 (10.3)	1,209 (15.0)
Education (%)					0.222
	9–11th grade	1,110 (13.3)	35 (12.1)	1,075 (13.3)
	College graduate or above	1,794 (21.4)	76 (26.2)	1,718 (21.3)
	High school graduate	1,865 (22.3)	65 (22.4)	1,800 (22.3)
	Less than 9th grade	1,060 (12.7)	28 (9.7)	1,032 (12.8)
	Some college or AA degree	2,537 (30.3)	86 (29.7)	2,451 (30.3)
Alcohol (%)					0.84
	No	3,351 (40.1)	114 (39.3)	3,237 (40.1)
	Yes	5,015 (59.9)	176 (60.7)	4,839 (59.9)
BMI (mean (SD))		30.24 (7.88)	29.87 (6.85)	30.26 (7.92)	0.409
High blood pressure (%)					< 0.001
	No	5,100 (61.0)	110 (37.9)	4,990 (61.8)
	Yes	3,266 (39.0)	180 (62.1)	3,086 (38.2)
Diabetes (%)					< 0.001
	Borderline	228 (2.7)	11 (3.8)	217 (2.7)
	No	6,888 (82.3)	204 (70.3)	6,684 (82.8)
	Yes	1,250 (14.9)	75 (25.9)	1,175 (14.5)
Folic (mean (SD))		148.61 (145.69)	143.41 (133.88)	148.80 (146.10)	0.536
Smoke (%)					0.02
	No	6,162 (73.7)	196 (67.6)	5,966 (73.9)
	Yes	2,204 (26.3)	94 (32.4)	2,110 (26.1)
Sleep disorders (%)					0.035
	No	6,011 (71.9)	192 (66.2)	5,819 (72.1)
	Yes	2,355 (28.1)	98 (33.8)	2,257 (27.9)

↓ Table 1. Comparison of Baseline Characteristics in Groups With and Without Breast Cancer

Variable

Group

Overall

Breast cancer

No cancer

P-value

BMI: body mass index; SD: standard deviation.

8,366

290

8,076

Gender (%)

Female

8,366 (100.0)

290 (100.0)

8,076 (100.0)

Age (mean (SD))

50.97 (17.66)

67.69 (10.81)

50.37 (17.56)

< 0.001

Race (%)

< 0.001

Mexican American

1,439 (17.2)

33 (11.4)

1,406 (17.4)

Non-Hispanic Black

2,002 (23.9)

51 (17.6)

1,951 (24.2)

Non-Hispanic White

2,633 (31.5)

150 (51.7)

2,483 (30.7)

Other Hispanic

1,053 (12.6)

26 (9.0)

1,027 (12.7)

Other Race including multi-racial

1,239 (14.8)

30 (10.3)

1,209 (15.0)

Education (%)

0.222

9–11th grade

1,110 (13.3)

35 (12.1)

1,075 (13.3)

College graduate or above

1,794 (21.4)

76 (26.2)

1,718 (21.3)

High school graduate

1,865 (22.3)

65 (22.4)

1,800 (22.3)

Less than 9th grade

1,060 (12.7)

28 (9.7)

1,032 (12.8)

Some college or AA degree

2,537 (30.3)

86 (29.7)

2,451 (30.3)

Alcohol (%)

0.84

3,351 (40.1)

114 (39.3)

3,237 (40.1)

Yes

5,015 (59.9)

176 (60.7)

4,839 (59.9)

BMI (mean (SD))

30.24 (7.88)

29.87 (6.85)

30.26 (7.92)

0.409

High blood pressure (%)

< 0.001

5,100 (61.0)

110 (37.9)

4,990 (61.8)

Yes

3,266 (39.0)

180 (62.1)

3,086 (38.2)

Diabetes (%)

< 0.001

Borderline

228 (2.7)

11 (3.8)

217 (2.7)

6,888 (82.3)

204 (70.3)

6,684 (82.8)

Yes

1,250 (14.9)

75 (25.9)

1,175 (14.5)

Folic (mean (SD))

148.61 (145.69)

143.41 (133.88)

148.80 (146.10)

0.536

Smoke (%)

0.02

6,162 (73.7)

196 (67.6)

5,966 (73.9)

Yes

2,204 (26.3)

94 (32.4)

2,110 (26.1)

Sleep disorders (%)

0.035

6,011 (71.9)

192 (66.2)

5,819 (72.1)

Yes

2,355 (28.1)

98 (33.8)

2,257 (27.9)

↓ **Table 2.** Association of Sleep Disorders and Breast Cancer
	Model 1	Model 2	Model 3
OR: odds ratio; 95% CI: 95% confidence interval.
No sleep disorders	Reference		Reference		Reference
Sleep disorders	1.096 (0.775, 1.551)	0.604	0.859 (0.592, 1.247)	0.426	0.814 (0.553, 1.196)	0.298

↓ Table 2. Association of Sleep Disorders and Breast Cancer

Model 1

Model 2

Model 3

OR (95% CI)

OR: odds ratio; 95% CI: 95% confidence interval.

No sleep disorders

Reference

Sleep disorders

1.096 (0.775, 1.551)

0.604

0.859 (0.592, 1.247)

0.426

0.814 (0.553, 1.196)

0.298

↓ **Table 3.** MR Results of Sleep Disorders and ER+ Breast Cancer
ID.exposure	ID.outcome	Exposure	Outcome	MR method	OR (95% CI)	P-value
ER+: estrogen receptor-positive; MR: Mendelian randomization; OR: odds ratio; 95% CI: 95% confidence interval.
finn-b-F5_SLEEP	ieu-a-1127	Sleep disorders	ER+ breast cancer	MR-Egger	0.98(0.93, 1.03)	0.568
finn-b-F5_SLEEP	ieu-a-1127	Sleep disorders	ER+ breast cancer	Weighted median	0.98(0.94, 1.02)	0.349
finn-b-F5_SLEEP	ieu-a-1127	Sleep disorders	ER+ breast cancer	Inverse variance weighted	0.98(0.94, 1.02)	0.304
finn-b-F5_SLEEP	ieu-a-1127	Sleep disorders	ER+ breast cancer	Simple mode	0.98(0.93, 1.03)	0.537
finn-b-F5_SLEEP	ieu-a-1127	Sleep disorders	ER+ breast cancer	Weighted mode	0.98(0.94, 1.02)	0.465

↓ Table 3. MR Results of Sleep Disorders and ER+ Breast Cancer

ID.exposure

ID.outcome

Exposure

Outcome

MR method

OR (95% CI)

P-value

ER+: estrogen receptor-positive; MR: Mendelian randomization; OR: odds ratio; 95% CI: 95% confidence interval.

finn-b-F5_SLEEP

ieu-a-1127

Sleep disorders

ER+ breast cancer

MR-Egger

0.98(0.93, 1.03)

0.568

finn-b-F5_SLEEP

ieu-a-1127

Sleep disorders

ER+ breast cancer

Weighted median

0.98(0.94, 1.02)

0.349

finn-b-F5_SLEEP

ieu-a-1127

Sleep disorders

ER+ breast cancer

Inverse variance weighted

0.98(0.94, 1.02)

0.304

finn-b-F5_SLEEP

ieu-a-1127

Sleep disorders

ER+ breast cancer

Simple mode

0.98(0.93, 1.03)

0.537

finn-b-F5_SLEEP

ieu-a-1127

Sleep disorders

ER+ breast cancer

Weighted mode

0.98(0.94, 1.02)

0.465

↓ **Table 4.** MR Results of Sleep Disorders and ER− Breast Cancer
ID.exposure	ID.outcome	Exposure	Outcome	MR method	OR (95% CI)	P-value
ER−: estrogen receptor-negative; MR: Mendelian randomization; OR: odds ratio; 95% CI: 95% confidence interval.
finn-b-F5_SLEEP	ieu-a-1128	Sleep disorders	ER− breast cancer	MR Egger	1.055 (0.978, 1.139)	0.301
finn-b-F5_SLEEP	ieu-a-1128	Sleep disorders	ER− breast cancer	Weighted median	1.067 (0.997, 1.141)	0.061
finn-b-F5_SLEEP	ieu-a-1128	Sleep disorders	ER− breast cancer	Inverse variance weighted	1.070 (1.013, 1.130)	0.016
finn-b-F5_SLEEP	ieu-a-1128	Sleep disorders	ER− breast cancer	Simple mode	1.061 (0.963, 1.168)	0.319
finn-b-F5_SLEEP	ieu-a-1128	Sleep disorders	ER− breast cancer	Weighted mode	1.060 (0.986, 1.139)	0.213

↓ Table 4. MR Results of Sleep Disorders and ER− Breast Cancer

ID.exposure

ID.outcome

Exposure

Outcome

MR method

OR (95% CI)

P-value

ER−: estrogen receptor-negative; MR: Mendelian randomization; OR: odds ratio; 95% CI: 95% confidence interval.

finn-b-F5_SLEEP

ieu-a-1128

Sleep disorders

ER− breast cancer

MR Egger

1.055 (0.978, 1.139)

0.301

finn-b-F5_SLEEP

ieu-a-1128

Sleep disorders

ER− breast cancer

Weighted median

1.067 (0.997, 1.141)

0.061

finn-b-F5_SLEEP

ieu-a-1128

Sleep disorders

ER− breast cancer

Inverse variance weighted

1.070 (1.013, 1.130)

0.016

finn-b-F5_SLEEP

ieu-a-1128

Sleep disorders

ER− breast cancer

Simple mode

1.061 (0.963, 1.168)

0.319

finn-b-F5_SLEEP

ieu-a-1128

Sleep disorders

ER− breast cancer

Weighted mode

1.060 (0.986, 1.139)

0.213

↓ **Table 5.** Heterogeneity Testing of Sleep Disorders Genetic Variations in ER− Breast Cancer in a GWAS Dataset
ID.exposure	ID.outcome	Exposure	Outcome	Method	Q	Q_df	Q_pval
ER−: estrogen receptor-negative; GWAS: genome-wide association study; MR: Mendelian randomization.
finn-b-F5_SLEEP	ieu-a-1128	Sleep disorders	ER− breast cancer	MR Egger	0.231	2	0.891
finn-b-F5_SLEEP	ieu-a-1128	Sleep disorders	ER− breast cancer	Inverse variance weighted	0.489	3	0.921

↓ Table 5. Heterogeneity Testing of Sleep Disorders Genetic Variations in ER− Breast Cancer in a GWAS Dataset

ID.exposure

ID.outcome

Exposure

Outcome

Method

Q_df

Q_pval

ER−: estrogen receptor-negative; GWAS: genome-wide association study; MR: Mendelian randomization.

finn-b-F5_SLEEP

ieu-a-1128

Sleep disorders

ER− breast cancer

MR Egger

0.231

0.891

finn-b-F5_SLEEP

ieu-a-1128

Sleep disorders

ER− breast cancer

Inverse variance weighted

0.489

0.921

↓ **Table 6.** Pleiotropy of Sleep Disorders Genetic Variations in ER− Breast Cancer in a GWAS Dataset
ER−: estrogen receptor-negative; GWAS: genome-wide association study; SE: standard error.
ID.exposure	ID.outcome	Exposure	Outcome	Egger_intercept	SE	P-value
finn-b-F5_SLEEP	ieu-a-1128	Sleep disorders	ER− breast cancer	0.006	0.012	0.662

↓ Table 6. Pleiotropy of Sleep Disorders Genetic Variations in ER− Breast Cancer in a GWAS Dataset

ER−: estrogen receptor-negative; GWAS: genome-wide association study; SE: standard error.

ID.exposure

ID.outcome

Exposure

Outcome

Egger_intercept

P-value

finn-b-F5_SLEEP

ieu-a-1128

Sleep disorders

ER− breast cancer

0.006

0.012

0.662