Table 4.
XRCC1 Arg399Gln 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 | ||||||||||||
| Not stratified by ethnicity w/in study | 21 | 0.01 | 11 | 0.4 | 9 | 0.3 | ||||||
| Stratified by ethnicity within study ** | 23 | 0.02 | 12 | 0.3 | na | |||||||
| By Study Characteristic | ||||||||||||
| Continent | ||||||||||||
| North America | 7 | 0.01 | 1.1 (0.9, 1.3) | Ref | 2 | 0.6 | 1.2 (1.0, 1.5) | Ref | 2 | 0.1 | 1.2 (0.8, 1.7) | 1.1 (0.7, 1.7) |
| Europe | 11 | 0.2 | 1.1 (0.9, 1.3) | 1.0 (0.8, 1.3) | 5 | 0.5 | 0.8 (0.6, 1.0) | 0.7 (0.5, 0.9) | 5 | 0.8 | 1.1 (0.9, 1.4) | Ref |
| Asia | 3 | 0.1 | 1.1 (0.7, 1.9) | 1.0 (0.7, 1.6) | 4 | 0.7 | 1.0 (0.8, 1.3) | 0.8 (0.6, 1.1) | 2 | 0.6 | 1.9 (1.2, 2.9) | 1.7 (1.0, 2.7) |
| Ethnicity/nationality ** | ||||||||||||
| Single-ethnicity studies **,†† | 14 | 0.3 | 1.0 (0.9, 1.2) | Ref | 4 | 0.1 | 1.0 (0.8, 1.2) | Ref | 5 | 0.4 | 1.1 (0.9, 1.5) | Ref |
| Multi-ethnic studies †† | 2 | 0.01 | 1.2 (0.7, 2.1) | 1.2 (0.9, 1.7) | 1 | na | 0.9 (0.2, 3.4) | 0.9 (0.2, 3.5) | 0 | |||
| Unknown ethnicity | 7 | 0.1 | 1.1 (0.9, 1.3) | 1.1 (0.8, 1.4) | 7 | 0.6 | 0.9 (0.7, 1.1) | 0.9 (0.6, 1.3) | 4 | 0.2 | 1.3 (1.1, 1.7) | 1.2 (0.8, 1.8) |
| White >=99% ‡‡ | 10 | 0.6 | 1.0 (0.9, 1.1) | Ref | 2 | 0.2 | 0.9 (0.6, 1.2) | na | 5 | 0.4 | 1.1 (0.9, 1.5) | na |
| African American >=99% | 2 | 0.03 | 1.1 (0.5, 2.5) | 1.1 (0.7, 1.8) | 1 | na | 2.1 (1.1, 3.9) | 0 | ||||
| Han >=99% | 2 | 0.2 | 1.4 (0.8, 2.5) | 1.5 (0.8, 2.5) | 1 | na | 1.0 (0.7, 1.4) | 0 | ||||
| Multi-ethnic studies | 2 | 0.01 | 1.2 (0.7, 2.1) | 1.3 (0.9, 1.8) | 1 | na | 0.9 (0.2, 3.4) | 0 | ||||
| HWE p-value ** | ||||||||||||
| Single-ethnicity (continuous) | 13 | 0.2 | 1.0 (0.9, 1.2) | 0.8 (0.5, 1.3) | 4 | 0.1 | 1.0 (0.8, 1.2) | 1.3 (0.2, 7.2) | 5 | 0.4 | 1.1 (0.9, 1.5) | 16.9 (0.4, 713) |
| p <0.05 | 0 | |||||||||||
| p< 0.10 | 1 | --- | 0.9 (0.6, 1.3) | na | 0 | 0 | ||||||
| p>=0.10 | 21 | 0.02 | 1.1 (1.0, 1.2) | 12 | 9 | |||||||
| Age | ||||||||||||
| Age non-missing | 20 | 0.01 | 1.1 (1.0, 1.2) | 1.0 (1.0, 1.0) | 10 | 0.3 | 1.0 (0.9, 1.1) | 1.0 (1.0, 1.0) | 9 | 0.3 | 1.2 (1.0, 1.5) | 1.0 (1.0, 1.1) |
| <= 47.9y §§ | 1 | --- | 0.8 (0.4, 1.6) | na | 5 | 0.3 | 0.9 (0.7, 1.1) | Ref | 0 | na | ||
| > 47.9 y | 19 | 0.01 | 1.1 (1.0, 1.2) | 5 | 0.4 | 1.1 (0.9, 1.3) | 1.2 (0.9, 1.7) | 9 | 0.3 | 1.2 (1.0, 1.5) | ||
| <=59y ** | 8 | 0.1 | 1.1 (0.9, 1.3) | Ref | 8 | 0.6 | 0.9 (0.7, 1.1) | Ref | 3 | 0.1 | 1.1 (0.8, 1.6) | Ref |
| >59y | 12 | 0.02 | 1.1 (0.9, 1.3) | 1.0 (0.8, 1.3) | 2 | 0.2 | 1.1 (0.9, 1.4) | 1.3 (1.0, 1.7) | 6 | 0.4 | 1.3 (1.0, 1.6) | 1.2 (0.8, 1.8) |
| At or below median | 12 | 0.1 | 1 (0.9, 1.2) | Ref | 5 | 0.3 | 0.9 (0.7, 1.1) | Ref | 5 | 0.4 | 1.2 (1.0, 1.5) | Ref |
| Above median | 8 | 0.02 | 1.2 (0.9, 1.4) | 1.1 (0.9, 1.4) | 5 | 0.4 | 1.1 (0.9, 1.3) | 1.2 (0.9, 1.7) | 4 | 0.2 | 1.3 (1.0, 1.8) | 1.1 (0.7, 1.6) |
| Gender | ||||||||||||
| Percent male (mixed gender only) | 13 | 0.1 | 1.0 (0.9, 1.2) | 1.4 (0.6, 3.5) | 4 | 0.7 | 1.0 (0.8, 1.3) | 0.9 (0.1, 8) | 6 | 0.1 | 1.3 (1.0, 1.5) | 1 (0.1, 11.4) |
| All female | 5 | 0.01 | 1.1 (0.8, 1.4) | Ref | 2 | 0.3 | 1.2 (0.9, 1.5) | Ref | 1 | -- | 0.9 (0.4, 1.8) | Ref |
| Mixed gender | 13 | 0.1 | 1.0 (0.9, 1.2) | 1.0 (0.7, 1.3) | 4 | 0.7 | 1.0 (0.8, 1.3) | 0.9 (0.6, 1.2) | 6 | 0.1 | 1.3 (1.0, 1.5) | 1.4 (0.7, 2.9) |
| All male | 3 | 0.7 | 1.2 (0.9, 1.6) | 1.1 (0.7, 1.7) | 4 | 0.7 | 0.7 (0.6, 1.0) | 0.6 (0.4, 0.9) | 2 | 0.7 | 1.3 (0.8, 2.2) | 1.5 (0.6, 3.6) |
| Study outcome | ||||||||||||
| Lung cancer | 6 | 0.4 | 1.0 (0.9, 1.1) | Ref | 1 | --- | 0.9 (0.6, 1.3) | Ref | 6 | 0.2 | 1.3 (1.1, 1.6) | Ref |
| Other cancer | 12 | 0.02 | 1.2 (1.0, 1.4) | 1.2 (1.0, 1.6) | 3 | 0.3 | 1.1 (0.9, 1.3) | 1.2 (0.8, 2) | 3 | 0.7 | 1.0 (0.7, 1.5) | 0.8 (0.5, 1.2) |
| Non-cancer disease | 0 | 1 | --- | 1.6 (0.6, 3.7) | 1.8 (0.7, 4.7) | 0 | ||||||
| Non-disease | 3 | 0.7 | 1.0 (0.8, 1.4) | 1.1 (0.7, 1.6) | 6 | 0.6 | 0.8 (0.6, 1.1) | 0.9 (0.6, 1.5) | 0 | |||
| Lung cancer | 6 | 0.4 | 1.0 (0.9, 1.1) | Ref | 1 | --- | 0.9 (0.6, 1.3) | na | 6 | 0.2 | 1.3 (1.1, 1.6) | Ref |
| All other | 15 | 0.04 | 1.2 (1.0, 1.3) | 1.2 (1.0, 1.5) | 10 | 0.3 | 1 (0.9, 1.2) | 3 | 0.7 | 1 (0.7, 1.5) | 0.8 (0.5, 1.2) | |
| MAF † | ||||||||||||
| MAF (cutpoints assigned by tertiles across SNP) | ||||||||||||
| 0.10–0.27 | 6 | 0.1 | 1.1 (0.7, 1.5) | Ref | 4 | 0.1 | 1.1 (0.9, 1.4) | Ref | 2 | 0.6 | 1.9 (1.2, 2.9) | Ref |
| >0.27–0.36 | 10 | 0.01 | 1.1 (1.0, 1.3) | 1.1 (0.8, 1.5) | 4 | 0.4 | 0.9 (0.6, 1.4) | 0.8 (0.5, 1.4) | 7 | 0.5 | 1.1 (0.9, 1.4) | 0.6 (0.4, 1.0) |
| >0.36–0.50 | 6 | 0.9 | 1 (0.8, 1.2) | 1 (0.7, 1.4) | 4 | 0.7 | 0.8 (0.7, 1.1) | 0.8 (0.5, 1.1) | 0 | |||
| MAF-assigned ethnicity | ||||||||||||
| White | 15 | 0.3 | 1.1 (0.9, 1.2) | Ref | 6 | 0.5 | 0.9 (0.7, 1.1) | Ref | 7 | 0.5 | 1.1 (0.9, 1.4) | Ref |
| African American ‡‡‡ | 3 | 0.1 | 1 (0.5, 1.8) | 0.9 (0.6, 1.5) | 1 | 2.1 (1.1, 3.9) | 2.4 (1.2, 4.7) | 0 | ||||
| Han | 3 | 0.1 | 1.1 (0.7, 1.9) | 1.0 (0.7, 1.5) | 4 | 0.7 | 1.0 0.8, 1.3) | 1.1 (0.8, 1.6) | 2 | 0.6 | 1.9 (1.2, 2.9) | 1.6 (1.0, 2.6) |
| Multi-ethnic studies | 2 | 0.01 | 1.2 (0.7, 2.1) | 1.2 (0.8, 1.7) | 1 | -- | 0.9 0.2, 3.4) | 1 (0.3, 4.1) | 0 | |||
| Smoking prevalence §§§ | ||||||||||||
| Continuous | 21 | 0.01 | 1.7 (0.6, 4.7) | 11 | 0.4 | 1.0 (0.9, 1.1) | 0.2 (0.1, 0.7) | 9 | 0.3 | 1.2 (1.0, 1.5) | 0.7 (0.2, 2.6) | |
| >0–0.507 | 5 | 0.2 | 1 (0.8, 1.2) | Ref | 9 | 0.5 | 1.0 (0.9, 1.2) | Ref | 6 | 0.4 | 1.3 (1.1, 1.6) | Ref |
| >0.507–1 | 16 | 0.01 | 1.1 (1.0, 1.3) | 1.1 (0.9, 1.5) | 2 | 0.8 | 0.7 (0.5, 1.1) | 0.7 (0.5, 1.1) | 3 | 0.3 | 0.9 (0.6, 1.4) | 0.7 (0.4, 1.1) |
Abbreviations: CI=Confidence interval, na=not applicable, HWE = Hardy Weinberg equilibrium PY=pack-years, ORz=control-only genotype-smoking odds ratio (bolded), N=number of studies, Ref=referent, Q=Cochran’s test of homogeneity, SNP=single nucleotide polymorphism, MAF=minor allele frequency, Arg=Arginine, Gln=Glutamine, Trp=Tryptophan, His=Histidine, Met=methionine, Asp=Aspartic acid, Asn=Asparagine
OR=Unadjusted odds ratio for XRCC1 Arg399Gln: XRCC1 Arg/Arg (ref) vs. any Gln, never moking (ref) vs. ever smoking, random effects estimates
OR=Unadjusted odds ratio for XRCC1 Arg399Gln: XRCC1 Arg/Arg (ref) vs. any Gln, not current smoker (ref) vs. current smoker, fixed effects estimates
OR=Unadjusted odds ratio for XRCC1 Arg399Gln: XRCC1 Arg/Arg (ref) vs. any Gln, lightest smokers (ref) vs. heaviest smokers [lightest excludes never smokers], fixed effects
PY contrast is between lightest non-zero category of pack-years (ref) vs. heaviest category of PY
Ratio of Odds Ratios: Compares odds ratio in given study characteristic stratum to the odds ratio in the designated reference stratum for that study characteristic by meta-regression
Studies that can be stratified by ethnicity are included as separate single-ethnicity studies; 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; Japan, Korea and China may include ethnic minorities.
Median of studies included in XRCC1 399 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: 56.51y SD: 9.84y]
Median proportion male in all studies (all SNPs, all smoking exposures): 0.69
For 399 ever-never 1 study from Hungary is included using MAF as proxy for ethnicity
Smoking prevalence is contrast-specific (defined as "ever", "current" or "heavier PY" as appropriate)