Table 3.
Genotype-smoking associations stratified by study design
| XRCC1 | ||||||||||
|---|---|---|---|---|---|---|---|---|---|---|
| Arg399Gln | Arg194Trp | Arg280His | ||||||||
| N | ORz (95% CI) |
Ratio of ORs (95%CI) † |
N | ORz (95% CI) * |
Ratio of ORs (95%CI) † |
N | ORz (95% CI)* |
Ratio of ORs (95%CI) † |
||
| Ever-never smoking | ||||||||||
| Case-based categories | ||||||||||
| Case-control | ||||||||||
| Population-based | 8 | 1.1 (0.9, 1.5) | Ref | 4 | 1.0 (0.9, 1.3) | Ref | 2 | 0.9 (0.7, 1.3) | Ref | |
| Hospital-based | 9 | 1.0 (0.9, 1.2) | 0.9 (0.7, 1.2) | 5 | 0.9 (0.8, 1.1) | 0.9 (0.7, 1.2) | 2 | 1.1 (0.8, 1.4) | 1.2 (0.8, 1.8) | |
| Other | 1 | 0.9 (0.6, 1.3) | 0.8 (0.4, 1.3) | 2 | 1.1 (0.9, 1.5) | 1.1 (0.8, 1.5) | 0 | |||
| Other | 3 | 1.0 (0.8, 1.4) | 0.9 (0.6, 1.4) | 1 | 0.7 (0.3, 1.4) | 0.7 (0.3, 1.4) | 1 | 0.5 (0.2, 1.1) | 0.5 (0.2, 1.3) | |
| Non-case-based categories | ||||||||||
| Case-control | ||||||||||
| Population controls | 8 | 1.1 (0.9, 1.5) | Ref | 4 | 1.0 (0.9, 1.3) | Ref | 2 | 0.9 (0.7, 1.3) | Ref | |
| Patient controls ‡ | 6 | 1.1 (0.9, 1.2) | 0.9 (0.7, 1.3) | 5 | 0.9 (0.8, 1.1) | 0.9 (0.7, 1.2) | 2 | 1.1 (0.8, 1.4) | 1.2 (0.8, 1.8) | |
| Non-patient controls§ | 4 | 0.9 (0.8, 1.1) | 0.8 (0.6, 1.1) | 2 | 1.1 (0.9, 1.5) | 1.1 (0.8, 1.5) | 0 | |||
| Other | 3 | 1.0 (0.8, 1.4) | 0.9 (0.6, 1.4) | 1 | 0.7 (0.3, 1.4) | 0.7 (0.3, 1.4) | 1 | 0.5 (0.2, 1.1) | 0.5 (0.2, 1.3) | |
| XRCC1 | |||||||||
|---|---|---|---|---|---|---|---|---|---|
| Arg399Gln | Arg194Trp | Arg280His | |||||||
| N | ORz (95% CI) |
Ratio of ORs (95%CI) † |
N | ORz (95% CI) * |
Ratio of ORs (95%CI) † |
N | ORz (95% CI) * |
Ratio of ORs (95%CI) † |
|
| Current-not current smoking | |||||||||
| Case-based categories | |||||||||
| Case-control | |||||||||
| Population-based | 1 | 1.2 (1.0, 1.5) | Ref | 1 | 1.1 (0.8, 1.6) | NA | 1 | 0.9 (0.6, 1.4) | NA |
| Hospital-based | 3 | 0.9 (0.7, 1.2) | 0.7 (0.5, 1.0) | 2 | 0.9 (0.7, 1.3) | 0 | |||
| Unknown | 1 | 1.6 (0.7, 3.7) | 1.3 (0.5, 3.2) | 1 | 0.9 (0.4, 2.2) | 1 | 1.1 (0.2, 5.8) | ||
| Other | 6 | 0.8 (0.6, 1.1) | 0.7 (0.5, 1.0) | 2 | 1.5 (0.8, 2.7) | 2 | 0.5 (0.2, 1.0) | ||
| Non-case-based categories | |||||||||
| Case-control | |||||||||
| Population controls | 1 | 1.2 (1.0, 1.5) | Ref | 1 | 1.1 (0.8, 1.6) | NA | 1 | 0.9 (0.6, 1.4) | NA |
| Patient controls ‡ | 2 | 0.8 (0.6, 1.2) | 0.7 (0.5, 1.0) | 1 | 1.1 (0.6, 2.1) | 0 | |||
| Non-patient controls § | 1 | 1.0 (0.7, 1.5) | 0.8 (0.5, 1.3) | 1 | 0.8 (0.6, 1.2) | 0 | |||
| Unknown | 1 | 1.6 (0.7, 3.7) | 1.3 (0.5, 3.2) | 1 | 0.9 (0.4, 2.2) | 1 | 1.1 (0.2, 5.8) | ||
| Other | 6 | 0.8 (0.6, 1.1) | 0.7 (0.5, 1.0) | 2 | 1.5 (0.8, 2.7) | 2 | 0.5 (0.2, 1.0) | ||
| XRCC1 | |||||||||
|---|---|---|---|---|---|---|---|---|---|
| Arg399Gln | Arg194Trp | Arg280His | |||||||
| N | ORz (95% CI) * |
Ratio of ORs (95%CI) † |
N | ORz (95% CI) * |
Ratio of ORs (95%CI) † |
N | ORz (95% CI) * |
Ratio of ORs (95%CI) † |
|
| Pack-years | |||||||||
| Case-based categories | |||||||||
| Case-control | |||||||||
| Population-based | 2 | 0.9 (0.6, 1.4) | Ref | 0 | NA | 1 | 0.5 (0.2, 1.5) | NA | |
| Hospital-based | 7 | 1.3 (1.1, 1.6) | 1.5 (0.9, 2.4) | 2 | 1.1 (0.7, 1.6) | 2 | 1.1 (0.7, 1.8) | ||
| Non-case-based categories | |||||||||
| Case-contrl | |||||||||
| Population controls | 2 | 0.9 (0.6, 1.4) | Ref | 0 | NA | 1 | 0.5 (0.2, 1.5) | NA | |
| Patient controls ‡ | 4 | 1.4 (1.1, 1.7) | 1.5 (0.9, 2.5) | 2 | 1.1 (0.7, 1.6) | 2 | 1.1 (0.7, 1.8) | ||
| Non-patient controls § | 3 | 1.3 (0.9, 1.8) | 1.4 (0.8, 2.5) | 0 | 0 | ||||
| XPD | XRCC3 | ||||||||
|---|---|---|---|---|---|---|---|---|---|
| Lys751Gln | Asp312Asn | Thr241Met | |||||||
| N | ORz (95% CI) * | Ratio of ORs (95%CI) † |
N | ORz (95% CI)* | Ratio of ORs (95%CI) † |
N | ORz (95% CI) * | Ratio of ORs (95%CI) † |
|
| Ever-never smoking | |||||||||
| Case-based categories | |||||||||
| Case-control | |||||||||
| Population-based | 4 | 1.0 (0.8, 1.1) | Ref | 2 | 1.3 (1.0, 1.8) | Ref | 2 | 1.0 (0.8, 1.3) | Ref |
| Hospital-based | 7 | 0.9 (0.8, 1.1) | 0.9 (0.7, 1.2) | 7 | 1.0 (0.9, 1.2) | 0.8 (0.6, 1.1) | 4 | 1.0 (0.7, 1.3) | 1.0 (0.6, 1.4) |
| Other | 0 | 0 | 0 | ||||||
| Other | 1 | 1.0 (0.6, 1.6) | 1.0 (0.6, 1.7) | 0 | 3 | 1.2 (0.9, 1.6) | 1.2 (0.8, 1.8) | ||
| Non-case-based categories | |||||||||
| Case-control | |||||||||
| Population controls | 4 | 1.0 (0.8, 1.1) | Ref | 2 | 1.3 (1.0, 1.8) | Ref | 2 | 1.0 (0.8, 1.3) | Ref |
| Patient controls ‡ | 3 | 0.8 (0.6, 1.1) | 0.8 (0.5, 1.2) | 3 | 1.1 (0.9, 1.3) | 0.8 (0.6, 1.1) | 4 | 1.0 (0.7, 1.3) | 1.0 (0.6, 1.4) |
| Non-patient controls § | 4 | 1.0 (0.8, 1.2) | 1.0 (0.7, 1.4) | 4 | 1.0 (0.8, 1.2) | 0.7 (0.5, 1.1) | 0 | ||
| Other | 1 | 1.0 (0.6, 1.6) | 1.0 (0.5, 1.7) | 0 | 3 | 1.2 (0.9, 1.6) | 1.2 (0.8, 1.8) | ||
| XPD | XRCC3 | ||||||||
|---|---|---|---|---|---|---|---|---|---|
| Lys751Gln | Asp312Asn | Thr241Met | |||||||
| N | ORz (95% CI) * | Ratio of ORs (95%CI) † |
N | ORz (95% CI)* | Ratio of ORs (95%CI) † |
N | ORz (95% CI) * | Ratio of ORs (95%CI) † |
|
| Current-not current smoking | |||||||||
| Case-based categories | |||||||||
| Case-control | |||||||||
| Population-based | 1 | 1.0 (0.7, 1.3) | NA | 0 | 1 | 1.0 (0.7, 1.5) | Ref | ||
| Hospital-based | 1 | 0.7 (0.5, 1.2) | 1 | 1.1 (0.7, 1.9) | NA | 2 | 0.9 (0.6, 1.2) | 0.8 (0.5, 1.4) | |
| Other | 0 | 0 | 1 | 2.0 (0.6, 6.6) | 2.0 (0.6, 6.8) | ||||
| Other | 4 | 1.4 (1.0, 1.8) | 0 | 3 | 0.9 (0.6, 1.2) | 0.8 (0.5, 1.4) | |||
| Non-case-based categories | |||||||||
| Case-control | |||||||||
| Population controls | 1 | 1.0 (0.7, 1.3) | NA | 0 | 1 | 1.0 (0.7, 1.5) | Ref | ||
| Patient controls ‡ | 1 | 0.7 (0.5, 1.2) | 1 | 1.1 (0.7, 1.9) | NA | 2 | 0.9 (0.6, 1.2) | 0.8 (0.5, 1.4) | |
| Non-patient controls § | 0 | 0 | 1 | 2.0 (0.6, 6.6) | 2.0 (0.6, 6.8) | ||||
| Other | 4 | 1.4 (1.0, 1.8) | 0 | 3 | 0.9 (0.6, 1.2) | 0.8 (0.5, 1.4) | |||
| XPD | XRCC3 | ||||||||
|---|---|---|---|---|---|---|---|---|---|
| Lys751Gln | Asp312Asn | Thr241Met | |||||||
| N | ORz (95% CI) * | Ratio of ORs (95%CI) † |
N | ORz (95% CI)* | Ratio of ORs (95%CI) † |
N | ORz (95% CI) * | Ratio of ORs (95%CI) † |
|
| Pack-years | |||||||||
| Case-based categories | |||||||||
| Case-control | |||||||||
| Population-based | 2 | 0.8 (0.5, 1.3) | Ref | 0 | 1 | 0.8 (0.4, 1.4) | NA | ||
| Hospital-based | 5 | 1.3 (0.8, 2.1) | 1.5 (0.7, 3.5) | 4 | 1.1 (0.8, 1.5) | NA | 3 | 0.8 (0.5, 1.3) | |
| Other | 0 | 0 | 0 | ||||||
| Non-case-based categories | |||||||||
| Case-control | |||||||||
| Population controls | 2 | 0.8 (0.5, 1.3) | Ref | 0 | 1 | 0.8 (0.4, 1.4) | NA | ||
| Patient controls ‡ | 2 | 1.0 (0.6, 1.6) | 1.2 (0.5, 2.6) | 1 | 0.9 (0.5, 1.4) | NA | 2 | 0.8 (0.5, 1.3) | |
| Non-patient controls § | 3 | 1.6 (0.8, 3.1) | 2.0 (0.9, 4.3) | 3 | 1.3 (0.9, 1.8) | 1 | 1.1 (0.4, 2.7) | ||
Abbreviations: CI=Confidence interval, HWE = Hardy Weinberg equilibrium, MAF=minor allele frequency, na=not applicable, ORz=control-only genotype-smoking odds ratio, PY=pack-years, N=number of studies, Ref=referent, Q=Cochran’s test of homogeneity, Arg=Arginine, Gln=Glutamine, Trp=Tryptophan, His=Histidine, Met=methionine, Asp=Aspartic acid, Asn=Asparagine
Unadjusted OR (95% CI): Genotype contrast for all SNPs is A/A (ref) vs. any a, where A is the more common allele and a is the less common; random effects for XRCC1 Arg399Gln ever-never & XPD Lys751Gln, fixed effects for others
Ratio of Odds Ratios: Meta-regression used to compare odds ratios in given study design stratum to the odds ratio in the designated reference stratum
Patient controls: controls are persons attending a hospital or disease clinic for treatment or diagnosis, does not include patients at wellness or check-up clinics
Non-patient controls: Case-control study participants who are not patients (i.e. not treated at hospital or disease clinic); they may be friend and family controls, cohort members in a nested case-control etc.; also excludes population-based controls