Table 6.
XRCC3 Thr241Met 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 | |||||||||||||
| 9 | 0.5 | 1.0 (0.9, 1.2) | 7 | 0.7 | 0.9 (0.8, 1.1) | 4 | 0.7 | 0.8 (0.6, 1.2) | |||||
| By Study Characteristic | |||||||||||||
| Continent | |||||||||||||
| North America | 2 | 0.1 | 0.9 (0.6, 1.3) | Ref | 1 | --- | 0.8 (0.5, 1.2) | na | 2 | 0.3 | 0.7 (0.4, 1.3) | Ref | |
| Europe | 7 | 0.7 | 1.1 (0.9, 1.3) | 1.1 (0.8, 1.7) | 5 | 0.9 | 0.9 (0.7, 1.1) | 2 | 0.6 | 0.9 (0.6, 1.4) | 1.2 (0.6, 2.5) | ||
| Asia | 0 | 1 | --- | 2.0 (0.6, 6.6) | 0 | ||||||||
| Ethnicity/nationality | |||||||||||||
| Single-ethnicity studies ** | 3 | 0.7 | 0.8 (0.6, 1.1) | Ref | 3 | 0.3 | 0.8 (0.6, 1.1) | Ref | 2 | 0.9 | 1.0 (0.6, 1.7) | na | |
| Multi-ethnic studies †† | 2 | 0.2 | 1.0 (0.7, 1.3) | 1.2 (0.8, 1.9) | 1 | --- | 1.0 (0.7, 1.5) | 1.2 (0.7, 2) | 1 | --- | 0.6 (0.3, 1.2) | ||
| Unknown ethnicity | 4 | 0.9 | 1.2 (1.0, 1.5) | 1.5 (1.0, 2.2) | 3 | 0.7 | 0.9 (0.7, 1.3) | 1.1 (0.7, 1.7) | 1 | --- | 0.8 (0.4, 1.4) | ||
| White >=99% ‡‡ | 3 | 0.7 | 0.8 (0.6, 1.1) | Ref | 2 | 0.9 | 0.8 (0.6, 1.1) | Ref | 2 | 0.9 | 1.0 (0.6, 1.7) | na | |
| Han >=99% | 0 | 1 | --- | 2.0 (0.6, 6.6) | 0 | ||||||||
| HWE p-value | |||||||||||||
| Continuous (single ethnicity) | 3 | 0.7 | 0.8 (0.6, 1.1) | 1.0 (0.3, 3.4) | 3 | 0.3 | 0.8 (0.6, 1.1) | 0.4 (0.1, 1.6) | 2 | 0.9 | 1.0 (0.6, 1.7) | ||
| HWE p <0.05 | 0 | 1 | --- | 2.0 (0.6, 6.6) | na | 0 | na | ||||||
| HWE p <0.10 | 0 | na | 1 | --- | 2.0 (0.6, 6.6) | na | 0 | na | |||||
| HWE p >=0.10 | 9 | 0.5 | 1.0 (0.9, 1.2) | 6 | 0.9 | 0.9 (0.7, 1.1) | 4 | 0.7 | 0.8 (0.6, 1.2) | ||||
| Age | |||||||||||||
| Age non-missing | 9 | 0.5 | 1.0 (0.9, 1.2) | 1.0 (1.0, 1.0) | 7 | 0.7 | 0.9 (0.8, 1.1) | 0.9 (0.8, 1.1) | 4 | 0.7 | 0.8 (0.6, 1.2) | 0.9 (0.8, 1.1) | |
| <= 47.9y §§ | 1 | --- | na | 2 | 0.6 | 0.8 (0.6, 1.1) | Ref | 0 | na | ||||
| > 47.9 y | 8 | 0.4 | 1.0 (0.9, 1.2) | 5 | 0.6 | 1.0 (0.8, 1.2) | 1.2 (0.8, 1.9) | 4 | 0.7 | 0.8 (0.6, 1.2) | |||
| <=59y *** | 5 | 0.3 | 1 (0.8, 1.2) | Ref | 6 | 0.9 | 0.9 (0.7, 1.1) | na | 1 | --- | 1.1 (0.4, 2.7) | na | |
| >59y | 4 | 0.7 | 1.1 (0.9, 1.5) | 1.2 (0.8, 1.6) | 1 | --- | 2.0 (0.6, 6.6) | 3 | 0.5 | 0.8 (0.5, 1.1) | |||
| At or below median | 5 | 0.3 | 1.0 (0.8, 1.2) | Ref | 4 | 0.8 | 0.8 (0.7, 1.1) | Ref | 3 | 0.8 | 0.9 (0.6, 1.4) | na | |
| Above median | 4 | 0.7 | 1.1 (0.9, 1.5) | 1.2 (0.8, 1.6) | 3 | 0.5 | 1.0 (0.8, 1.4) | 1.2 (0.8, 1.8) | 1 | --- | 0.6 (0.3, 1.2) | ||
| Gender | |||||||||||||
| Percent male, mixed gender only | 6 | 0.3 | 1 (0.9, 1.3) | 1.1 (0.1, 12.6) | 4 | 0.5 | 1.0 (0.8, 1.3) | 0.1 (0, 3.4) | |||||
| All female | 0 | 0 | 0 | ||||||||||
| Mixed gender | 6 | 0.3 | 1.0 (0.9, 1.3) | Ref | 4 | 0.5 | 1.0 (0.8, 1.3) | Ref | 3 | 0.6 | 0.8 (0.5, 1.1) | na | |
| All male | 3 | 0.8 | 1.0 (0.8, 1.4) | 1.0 (0.7, 1.4) | 3 | 0.8 | 0.8 (0.6, 1.1) | 0.9 (0.6, 1.3) | 1 | --- | 1.0 (0.5, 1.9) | ||
| Study outcome | |||||||||||||
| Lung cancer | 0 | 0 | 1 | --- | 1.1 (0.4, 2.7) | na | |||||||
| Other cancer | 5 | 0.4 | 1 (0.8, 1.2) | Ref | 4 | 0.5 | 1.0 (0.7, 1.2) | Ref | 3 | 0.5 | 0.8 (0.5, 1.1) | ||
| Non-cancer disease | 0 | 0 | 0 | ||||||||||
| Non-disease | 4 | 0.7 | 1.2 (0.9, 1.6) | 1.2 (0.8, 1.7) | 3 | 0.7 | 0.9 (0.6, 1.2) | 0.9 (0.6, 1.3) | 0 | ||||
| Lung cancer | 0 | 0 | na | 1 | --- | 1.1 (0.4, 2.7) | na | ||||||
| All other | 9 | 0.5 | 1.0 (0.9, 1.2) | na | 6 | 0.7 | 0.9 (0.8, 1.1) | 3 | 0.5 | 0.8 (0.5, 1.1) | |||
| MAF | |||||||||||||
| MAF non-missing | 9 | 0.5 | 1.0 (0.9, 1.2) | 0.9 (0, 235.8) | 7 | 0.7 | 0.9 (0.8, 1.1) | 0.2 (0, 4.6) | 4 | 0.7 | 0.8 (0.6, 1.2) | 0 (0, 45050) | |
| MAF (cutpoints assigned by median across SNP) | |||||||||||||
| 0.01–0.37 | 5 | 0.3 | 1.0 (0.8, 1.3) | Ref | 2 | 0.1 | 0.9 (0.6, 1.4) | Ref | 4 | 0.7 | 0.8 (0.6, 1.2) | na | |
| >0.37–0.50 | 4 | 0.5 | 1.0 (0.8, 1.3) | 1.0 (0.7, 1.4) | 5 | 0.9 | 0.9 (0.7, 1.1) | 1.0 (0.6, 1.7) | 0 | ||||
| MAF-assigned ethnicity | |||||||||||||
| White | 7 | 0.5 | 1.1 (0.9, 1.3) | Ref | 5 | 0.9 | 0.9 (0.7, 1.1) | na | 3 | 0.8 | 0.9 (0.6, 1.4) | na | |
| Han | 0 | 1 | --- | 2.0 (0.6, 6.6) | 0 | ||||||||
| Multi-ethnic studies | 2 | 0.2 | 1.0 (0.7, 1.3) | 0.9 (0.7, 1.3) | 1 | --- | 1.0 (0.7, 1.5) | 1 | --- | 0.6 (0.3, 1.2) | |||
| Smoking prevalence 13 | |||||||||||||
| Continuous | 9 | 0.5 | 1.0 (0.9, 1.2) | 0.1 (0, 1.8) | 7 | 0.7 | 0.9 (0.8, 1.1) | 0.5 (0.1, 3.1) | 4 | 0.7 | 0.8 (0.6, 1.2) | 2.4 (0.1, 56.6) | |
| >0–0.507 | 0 | na | 6 | 0.7 | 0.9 (0.8, 1.2) | na | 2 | 0.5 | 0.7 (0.4, 1.1) | na | |||
| >0.507–1 | 9 | 0.5 | 1.0 (0.9, 1.2) | 1 | --- | 0.8 (0.6, 1.2) | 2 | 0.9 | 1.0 (0.6, 1.7) | ||||
Abbreviations: CI=Confidence interval, na=not applicable, HWE = Hardy Weinberg equilibrium, PY=pack-years, ORz=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 XRCC3 Thr241Met: Thr/Thr (ref) vs. any Met, never smoking (ref) vs. ever smoking, fixed effects
OR=Unadjusted odds ratio for XRCC3 Thr241Met: Thr/Thr (ref) vs. any Met, not current smoker (ref) vs. current smoker, fixed effects
OR=Unadjusted odds ratio for XRCC3 Thr241Met: Thr/Thr (ref) vs. any Met, 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 odds ratio in given study characteristic stratum to the odds ratio 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)