Table 5.

XPD Lys751Gln and Smoking: Overall and by study characteristics

	Ever-never *				Current-Not current †				PY ‡,§
	N	Q p- value	ORz (95% CI)	Ratio of ORs (95% CI) □	N	Q p- value	ORz (95% CI)	Ratio of ORs (95% CI)	N	Q p-value	ORz (95% CI)	Ratio of ORs (95% CI)
Overall
	12	0.5	0.9 (0.8, 1.1)		6	0.2	1.1 (0.9, 1.3)		7	0.019	1.2 (1.0, 1.5)
By Study Characteristic
Continent
North America	4	0.4	0.9 (0.8, 1)	Ref	1	---	0.9 (0.7, 1.3)	Ref	3	0.006	1.5 (0.7, 3.2)	Ref
Europe	6	0.3	1.0 (0.8, 1.3)	1.2 (0.9, 1.5)	5	0.2	1.2 (0.9, 1.5)	1.2 (0.8, 1.8)	3	0.503	1.0 (0.7, 1.4)	0.7 (0.3, 1.5)
Asia	2	0.5	1.0 (0.6, 1.7)	1.1 (0.7, 1.9)	0				1	na	0.8 (0.3, 1.7)	0.5 (0.1, 1.9)
Ethnicity/nationality
Single-ethnicity studies **	6	0.3	1.0 (0.8, 1.2)	Ref	1	---	1.2 (0.8, 1.8)	na	5	0.097	1.4 (0.9, 2.1)	na
Multi-ethnic studies ††	2	0.6	0.8 (0.7, 1.0)	0.8 (0.6, 1.1)	1	---	0.9 (0.7, 1.3)		1	---	0.8 (0.5, 1.3)
Unknown ethnicity	4	0.7	1.0 (0.8, 1.3)	1.1 (0.8, 1.4)	4	0.1	1.1 (0.8, 1.5)		1	---	0.8 (0.4, 1.4)
White >=99% ‡‡	4	0.2	1.0 (0.8, 1.2)	Ref	1	---	1.2 (0.8, 1.8)	na	4	0.181	1.6 (1.0, 2.4)	na
African American >=99%	0			1.0 (0.6, 1.8)	0				0
Han >=99%	2	0.5	1.0 (0.6, 1.7)	0.8 (0.6, 1.1)	0				1	---	0.8 (0.3, 1.7)
HWE p-value
Continuous (single ethnicity)	6	0.3	1.0 (0.8, 1.2)	0.8 (0.5, 1.2)	1	---	1.2 (0.8, 1.8)	na	5	0.097	1.4 (0.9, 2.1)	2.2 (0, 93.7)
HWE p <0.05	1	---	1.1 (0.8, 1.7)	Ref	2	0.6	1.3 (0.9, 1.8)	Ref	0			na
HWE p <0.10	2	0.9	1.1 (0.8, 1.5)	Ref	2	0.6	1.3 (0.9, 1.8)	Ref	1	---	0.8 (0.4, 1.4)	na
HWE p >=0.10	10	0.4	0.9 (0.8, 1.0)	0.8 (0.6, 1.1)	4	0.1	1.0 (0.8, 1.3)	0.8 (0.5, 1.2)	6	0.022	1.2 (0.8, 1.9)
Age
Age non-missing (continuous)	12	0.5	0.9 (0.8, 1.1)	1.0 (1.0, 1.0)	6	0.2	1.1 (0.9, 1.3)	1.0 (1.0, 1.0)	7	0.019	1.1 (0.8, 1.7)	1.0 (0.9, 1.1)
<= 47.9y §§	0			na	3	0.5	1.4 (1.0, 1.9)	Ref	0			na
> 47.9 y	12	0.5	0.9 (0.8, 1.1)	0 (0, 0)	3	0.4	0.9 (0.7, 1.2)	0.7 (0.5, 1.0)	7	0.019	1.1 (0.8, 1.7)
<=59y ***	7	0.6	0.9 (0.8, 1.0)	Ref	6	0.2	1.1 (0.9, 1.3)	na	4	0.054	1.4 (0.8, 2.4)	Ref
>59y	5	0.2	1.0 (0.8, 1.2)	1.1 (0.9, 1.4)	0				3	0.362	0.9 (0.6, 1.2)	0.6 (0.3, 1.2)
At or below median	6	0.5	0.9 (0.8, 1.1)	Ref	3	0.5	1.4 (1.0, 1.9)	Ref	4	0.054	1.4 (0.8, 2.4)	Ref
Above median	6	0.3	1.0 (0.8, 1.1)	1.1 (0.9, 1.4)	3	0.4	0.9 (0.7, 1.2)	0.7 (0.5, 1.0)	3	0.362	0.9 (0.6, 1.2)	0.6 (0.3, 1.2)
Gender
Percent male, mixed gender only	8	0.9	1.0 (0.9, 1.2)	0.8 (0.3, 2.4)	2	0.3	1.5 (1.0, 2.3)	na	5	0.006	1.2 (0.7, 2)	0 (0, 0.1)
All female	2	0.1	0.9 (0.7, 1.1)	Ref	1	---	0.9 (0.7, 1.3)	Ref	1	na	0.9 (0.4, 1.9)	na
Mixed gender	8	0.9	1.0 (0.9, 1.2)	1.1 (0.9, 1.5)	2	0.3	1.5 (1.0, 2.3)	1.6 (0.9, 2.7)	5	0.006	1.2 (0.7, 2)
All male	2	0.2	0.7 (0.5, 1.1)	0.8 (0.5, 1.3)	3	0.2	1.0 (0.8, 1.4)	1.1 (0.7, 1.7)	1	na	1.3 (0.7, 2.5)
Study outcome
Lung cancer	3	0.5	1.0 (0.8, 1.2)	Ref	0				3	0.080	1.6 (0.8, 3.1)	Ref
Other cancer	8	0.2	0.9 (0.8, 1.1)	0.9 (0.7, 1.2)	2	0.4	0.9 (0.7, 1.2)	Ref	4	0.565	0.9 (0.7, 1.2)	0.5 (0.3, 0.9)
Non-cancer disease	0				0				0
Non-disease	1	---	1.0 (0.6, 1.6)	1.0 (0.6, 1.7)	4	0.7	1.3 (1.0, 1.8)	1.5 (1.0, 2.2)	0
Lung cancer	3	0.5	1.0 (0.8, 1.2)	Ref	0			na	3	0.080	1.6 (0.8, 3.1)	Ref
All other	9	0.3	0.9 (0.8, 1.1)	0.9 (0.7, 1.2)	6	0.2	1.1 (0.9, 1.3)		4	0.565	0.9 (0.7, 1.2)	0.5 (0.3, 0.9)
MAF
MAF non-missing	12	0.5	0.9 (0.8, 1.1)	1.3 (0.3, 6.2)	6	0.2	1.1 (0.9, 1.3)	0 (0, 3772.6)	7			1.2 (0, 45.7)
MAF (cutpoints assigned by median across SNP)
0.01–0.37	7	0.5	0.9 (0.8, 1.0)	Ref	2	0.3	1.0 (0.7, 1.3)	Ref	5	0.016	1.3 (0.8, 2.1)	Ref
>0.37–0.50	5	0.7	1.1 (0.9, 1.4)	1.2 (1.0, 1.6)	4	0.2	1.1 (0.9, 1.5)	1.1 (0.7, 1.8)	2	0.768	0.8 (0.5, 1.3)	0.7 (0.3, 1.5)
MAF-assigned ethnicity
White	8	0.4	1.0 (0.9, 1.2)	Ref	5	0.2	1.2 (0.9, 1.5)	na	5	0.052	1.3 (0.9, 2.1)	na
African American	0				0				0
Han	2	0.5	1.0 (0.6, 1.7)	1.0 (0.6, 1.7)	0			na	1	---	0.8 (0.3, 1.7)	na
Multi-ethnic studies	2	0.6	0.8 (0.7, 1.0)	0.8 (0.6, 1.0)	1	---	0.9 (0.7, 1.3)		1	---	0.8 (0.5, 1.3)
Smoking prevalence ‡‡‡
Continuous	12	0.5	0.9 (0.8, 1.1)	0.3 (0.1, 1.1)	6	0.2	1.1 (0.9, 1.3)	2 (0.5, 8.6)	7			0.3 (0, 7.8)
>0–0.507	3	0.9	1.2 (0.9, 1.6)	Ref	5	0.2	1.1 (0.9, 1.3)	na	5	0.010	1.0 (0.6, 1.6)	Ref
>0.507–1	9	0.5	0.9 (0.8, 1.0)	0.7 (0.5, 1.0)	1	---	1.2 (0.8, 1.8)		2	0.359	1.5 (0.9, 2.6)	1.6 (0.7, 3.9)

Abbreviations: CI=Confidence interval, na=not applicable, HWE = Hardy Weinberg equilibrium, PY=pack-years, OR_z=control-only genotype-smoking odds ratio,), N=number of studies, Ref=referent, Q=Cochran’s test of homogeneity, SNP=single nucleotide polymorphism, Arg=Arginine, Gln=Glutamine, Trp=Tryptophan, His=Histidine, Met=methionine, Asp=Aspartic acid, Asn=Asparagine

^*OR=Unadjusted odds ratio for XPD Lys751Gln: Lys/Lys (ref) vs. any Gln, never smoking (ref) vs. ever smoking, fixed effects

^†OR=Unadjusted odds ratio for XPD Lys751Gln: Lys/Lys (ref) vs. any Gln, not current smoker (ref) vs. current smoker, fixed effects

^‡OR=Unadjusted odds ratio for XPD Lys751Gln: Lys/Lys (ref) vs. any Gln, lightest non-zero smokers (ref) vs. heaviest smokers; stratified random effects

^§PY contrast is between lightest non-zero category of pack-years (ref) vs. heaviest category of PY

^□Ratio of Odds Ratios: Compares OR in given study characteristic stratum to the OR in the designated reference stratum for that study characteristic by meta-regression

^**Studies w 99%–100% of 1 ethnicity are classified as single-ethnicity

^††Only includes studies with explicitly stated ethnic makeup

^‡‡White = Caucasian, white or non-Hispanic white; African American = African American or black; Han = Han, Han Chinese or ethnic Chinese

^§§Median of studies included in XRCC1 751 current/not current smoker analyses.

^□□Categories based on thirds from studies included in XRCC1 399 PY analyses (<=59y, >59y–63y, >63y)

^***Median of all studies w age info (all SNPs) w age info [range:23.6–69y, mean: 56.7y SD: 9.8y]

^†††Median proportion male in all studies (all SNPs, all smoking exposures): 0.69

^‡‡‡Smoking prevalence is contrast-specific (defined as "ever", "current" or "heavier PY" as appropriate)