Global DNA methylation levels in white blood cell DNA from sisters discordant for breast cancer from the New York site of the Breast Cancer Family Registry

Figures & data

Table 1. Demographics, mutation status and DNA methylation levels of the study population, New York site of the BCFR

	Affected Sisters		Unaffected Sisters
	n = 273		n = 335
	N	Mean (SD) or %	N	Mean (SD) or %
Age
Continuous	273	49.6 (11.4)	335	48.2 (11.2)
Race^‡
White	169	62.6%	189	56.4%
Hispanic	67	24.8%	102	30.4%
Other	34	12.6%	44	13.1%
Smoking status
Current	15	5.5%	41	12.2%
Former	96	35.2%	101	30.1%
Never	162	59.3%	193	57.6%
BRCA1 Mutation
Positive	22	8.1%	13	3.9%
Negative	251	91.9%	322	96.1%
BRCA2 Mutation
Positive	12	4.4%	9	2.7%
Negative	261	95.6%	326	97.3%
[^3H]-methyl acceptance assay (DPM/μg)
Continuous	233	97111 (76348)	295	88030 (70841)
LUMA (% DNA meth)
Continuous	263	67.1 (7.6)	321	67.5 (7.3)

‡ Race information was not available for three unaffected subjects

Table 2. Correlation of the global DNA methylation measures between sisters discordant for breast cancer by blood cell type, New York site of the BCFR

	Granulocytes			Total White Blood Cells			Pooled Source
	N	r	p value	N	r	p value	N	r	p value
[^3H]-methyl acceptance assay (DPM/μg)	64	-0.08	0.51	134	0.24	0.006	198	0.19	0.006
LUMA (% DNA methylation)	80	0.21	0.06	155	0.13	0.10	235	0.16	0.01

Table 3. Conditional Logistic Regression analysis of global DNA methylation biomarkers and breast cancer risk (pooled and by source), New York site of the BCFR

DNA Methylation			Odds Ratios and 95% Confidence Intervals for Overall Pooled sample and Stratified by Source^a
											[^3H]-methyl acceptance assay ^b			Pooled (n = 458)			Granulocytes (n = 156)			Total WBC (n = 302)
OR	95% CI	OR	95% CI	OR	95% CI
Quartile (DPM/μg DNA)	Q4 (> 115215); lower overall methylation	1.81	0.99–3.32	2.42	0.86–6.83	1.51	0.68–3.38
	Q3 (68940 – 115215)	1.81	1.02–3.20	1.34	0.46–3.87	1.76	0.84–3.67
	Q2 (41692 – 68940)	0.82	0.46–1.46	0.91	0.42–2.00	0.67	0.28–1.61
	Q1 (≤ 41692); higher overall methylation	1		1		1
Continuous (log DPM/μg DNA)	1 unit change, less methylation	1.34	1.03–1.74	1.18	0.82–1.70	1.49	1.03–2.16
LUMA ^c			Pooled (n = 551)			Granulocytes (n = 201)			Total WBC (n = 350)
			OR	95% CI		OR	95% CI		OR	95% CI
	Quartile (DNA meth %)	Q1 (≤ 62.9), lower overall methylation	0.92	0.53–1.59		1.18	0.43–3.24		0.8	0.41–1.55
		Q2 (62.9 - 68.0)	0.71	0.40–1.24		1.12	0.39–3.21		0.58	0.29–1.14
		Q3 (68.0 - 73.0)	1.26	0.75–2.12		1.9	0.79–4.55		0.98	0.51–1.91
		Q4 (> 73.0); higher overall methylation	1			1			1
	Continuous	1 unit change, less methylation	1.00	0.97–1.02		1.02	0.97–1.07		0.99	0.96–1.02

^a OR = odds ratio, 95% CI = 95% confidence intervals; adjusted for age at blood draw and smoking status. ^bHigher values on assay mean lower DNA methylation. ^cLower values on assay mean lower DNA methylation

Figure 1. Global DNA methylation measured by [³H]-methyl acceptance assay and breast cancer risk (pooled and by source), for specimens collected less than two years and more than two years after breast cancer diagnosis in the New York site of the BCFR. The OR is per unit change in log DPM/μg DNA