Individual and joint contributions of genetic and methylation risk scores for enhancing lung cancer risk stratification: data from a population-based cohort in Germany

Table 3 Joint associations of GRS and MRS with LC incidence

Group	MRS risk group^a	GaRS risk group^a	Cases	Controls	OR (95%CI)
Group	MRS risk group^a	GaRS risk group^a	Cases	Controls	Model 1^b	Model 2^c	Model 3^d
All participants	Low	Low	8	368	Ref.	Ref.	Ref.
(N_case/control = 143/1460)		High	9	362	0.91 (0.33–2.51)	0.86 (0.31–2.38)	0.77 (0.25–2.40)
	High	Low	41	330	5.61 (2.62–13.51)	5.11 (2.36–12.37)	2.29 (0.92–6.32)
		High	85	400	9.08 (4.40–21.35)	7.88 (3.75–18.73)	3.50 (1.44–9.50)
	p trend				< 0.0001	< 0.0001	0.0005
Ever smokers	Low	Low	10	164	Ref.	Ref.	Ref.
(N_case/control = 123/712)		High	17	192	1.48 (0.62–3.67)	1.47 (0.61–3.70)	1.38 (0.51–3.95)
	High	Low	29	162	3.99 (1.78–9.61)	4.06 (1.80–9.87)	1.83 (0.68–5.25)
		High	67	194	7.19 ( 3.39-16.69	7.03 (3.26-16.57)	3.35 (1.32-9.30)
	p trend				< 0.0001	< 0.0001	0.0038
Heavy smokers	Low	Low	6	46	Ref.	Ref.	Ref.
(N_case/control = 69/205)		High	15	56	2.48 (0.76–9.01)	2.12 (0.62–8.02)	1.78 (0.50–6.89)
	High	Low	14	43	2.81 (0.82–10.77)	3.13 (0.88–12.52)	1.96 (0.53–8.03)
		High	34	60	4.01 (1.33–13.92)	4.44 (1.42–16.06)	3.58 (1.10–13.25)
	p trend				0.0225	0.0097	0.0319

GRS genetic risk score, MRS methylation risk score, LC lung cancer, OR odds ratio, CI confidence interval, Ref. reference category
^aThe GRS/MRS median value was used as cut-point for low-/high-risk groups
^bModel 1: adjusted for batch (3 subsets) and leukocyte composition
^cModel 2: like model 1, additionally adjusted for age and sex
^dModel 3: like model 2, additionally adjusted for smoking status and pack-years

ISSN: 1868-7083