Background
Methods
Study population
Data collection
Tobacco exposure information
Genotype analysis
Repair | Gene | exon/intron | Enzyme | Polymorphism* | Genotype | Fragment sizes (bp) | |
---|---|---|---|---|---|---|---|
NER |
XPC
| intron 9 | - | insertion 83 pb | - |
PAT -/-
PAT +/+ | 266 344 |
XPD
| exon 10 |
StyI | G23591A (rs 1799793) | Asp312Asn |
Asp/Asp
Asn/Asn
| 244+507 33+244+474 | |
XPD
| exon 23 |
PstI | A35931C (rs 13181) | Lys751Gln |
Lys/Lys
Gln/Gln
| 146+290 63+146+227 | |
BER |
XRCC1 | exon 10 |
MspI | G28152A (rs 25487) | Arg399Gln |
Arg/Arg
Gln/Gln
| 132+278+461 278+593 |
DSBR |
XRCC3 | exon 7 |
NcoI | C18067T (rs 861539) | Thr241Met |
Thr/Thr
Met/Met
| 136 39+97 |
Product | Primer sequence | Size (bp) | PCR Conditions |
---|---|---|---|
XPC (PAT) | (F) TAG CAC CCA GCA GTC AAA G (R) TGT GAA TGT GCT TAA TGC TG | 266/344 | 30 cycles: 94°C 30s, 58°C 30s, 72°C 30s |
XPD exon 10 | (F) CTG TTG GTG GGT GCC CGT ATC TGT TGG TCT (R) TAA TAT CGG GGC TCA CCC TGC AGC ACT TCC T | 751 | 40 cycles: 94°C 30s, 65°C 30s, 72°C 1 min |
XPD exon 23 | (F) GCC CGC TCT GGA TTA TAC G (R) CTA TCA TCT CCT GGC CCC C | 436 | 30 cycles: 94°C 30s, 64°C 30s, 72°C 45s |
XRCC1 | (F) CAG TGG TGC TAA CCT AAT C (R) AGT AGT CTG CTG GCT CTG G | 871 | 30 cycles: 94°C 30s, 64°C 30s, 72°C 1 min |
XRCC3 | (F) GCC TGG TGG TCA TCG ACT C (R) CAG GGC TCT GGA AGG CAC TGC TCA GCT CAC GCA cC | 136 | 30 cycles: 94°C 30s, 65°C 30s, 72°C 1 min |
Statistical analysis
Results
Subject characteristics
Variable | Cases (n = 516) n (%) | Controls (n = 533) n (%) |
P
a
|
---|---|---|---|
Gender | |||
Male | 456 (88.4) | 460 (86.3) | |
Female | 60 (11.6) | 73 (13.7) | 0.314 |
Age (yrs), mean (SD) | 64.79 (10.99) | 63.54 (11.33) | 0.090 |
Smoking Status | |||
Never | 1 (0.2) | 4 (0.7) | |
ETS exposed | 35 (6.8) | 141 (26.45) | |
Ever | 480 (93.0) | 388 (73.0) | < 0.001 |
Former | 222 (46.8) | 224 (60.1) | |
Current | 252 (53.2) | 149 (39.9) | < 0.001 |
Type of tobacco | |||
Only black | 359 (75.3) | 223 (60.6) | |
Only blond | 47 (9.8) | 84 (22.8) | |
Both | 71 (14.9) | 61 (16.6) | < 0.001 |
Pack-yearsb, mean (SD) | 62.85 (36.18) | 40.41 (38.95) | < 0.001 |
Family history of cancer | |||
No | 272 (57.3) | 317 (62.2) | |
Lung cancer | 57 (12.0) | 35 (6.9) | |
Other cancer | 146 (30.7) | 158 (31.0) | 0.019 |
Histological type | |||
Squamous cell carcinoma | 208 (40.3) | ||
Adenocarcinoma | 152 (29.5) | ||
Small cell carcinoma | 83 (16.1) | ||
Large cell carcinoma | 16 (3.1) | ||
Non-differentiated | 39 (7.6) | ||
Others | 7 (1.3) | ||
Clinical diagnosis | 2 (0.4) | ||
Missing | 9 (1.7) |
Analysis of the XPC PATgenotype
Repair | Gen | SNP | Genotype | Cases n (%) | Controls n (%) | Adjusteda OR [95% IC] |
P
|
P trend |
---|---|---|---|---|---|---|---|---|
NER
|
XPC
| PAT |
-/-
| 172 (33.3) | 190 (35.6) | Reference | ||
+/-
| 243 (47.1) | 259 (48.6) | 1.08 [0.79–1.47] | 0.627 | ||||
+/+
|
101 (19.6)
|
84 (15.8)
|
1.28 [0.85–1.92]
| 0.229 | 0.246 | |||
XPD
| Asp312Asn |
Asp/Asp
| 240 (46.5) | 260 (48.8) | Reference | |||
Asp/Asn
| 221 (42.8) | 230 (43.1) | 1.01 [0.76–1.35] | 0.934 | ||||
Asn/Asn
|
55 (10.7)
|
43 (8.1)
|
1.52 [0.91–2.51]
| 0.106 | 0.232 | |||
Lys751Gln |
Lys/Lys
| 222 (43.0) | 243 (45.6) | Reference | ||||
Lys/Gln
| 237 (45.9) | 240 (45.0) | 1.12 [0.84–1.50] | 0.437 | ||||
Gln/Gln
|
57 (11.1)
|
50 (9.4)
|
1.38 [0.85–2.25]
| 0.193 | 0.181 | |||
BER
|
XRCC
1
| Arg399Gln |
Arg/Arg
| 222 (43.0) | 217 (40.7) | Reference | ||
Arg/Gln
| 219 (42.5) | 234 (43.9) | 0.86 [0.63–1.16] | 0.320 | ||||
Gln/Gln |
75 (14.5)
|
82 (15.4)
|
0.87 [0.57–1.31]
| 0.500 | 0.672 | |||
DSBR
|
XRCC
3
| Thr241Met |
Thr/Thr
| 168 (41.7) | 178 (41.0) | Reference | ||
Thr/Met
| 185 (45.9) | 196 (45.2) | 1.06 [0.76–1.49] | 0.724 | ||||
Met/Met
|
50 (12.4)
|
60 (13.8)
|
0.92 [0.56–1.50]
| 0.898 | 0.898 |
Analysis of the Asp312Asn and Lys751Gln polymorphisms in the XPDgene
Analysis of the Arg399Gln polymorphism in the XRCC1gene
Analysis of the Thr241Met polymorphism in the XRCC3gene
Combined analysis of polymorphisms in DNA repair genes and lung cancer
Genotype 1 | Genotype 2 | Cases n(%) | Controls n(%) | Adjusteda OR [95% CI] |
P
|
P
interaction
|
---|---|---|---|---|---|---|
XPC PAT | XPD Lys751Gln | |||||
-/- |
Lys/Lys
| 72 (13.9) | 84 (15.8) | 1.00 (reference) | ||
+/+
|
Lys/Lys
| 36 (7.0) | 38 (7.1) | 1.10 [0.59–2.06] | 0.971 | |
+/+
|
Lys/Gln
| 49 (9.5) | 37 (6.9) | 1.63 [0.89–2.98] | 0.111 | |
+/+
|
Gln/Gln
|
16 (3.1)
|
9 (1.7)
|
2.25 [0.83–6.13]
| 0.202 | 0.202 |
XPC PAT | XRCC3 Thr241Met | |||||
-/- |
Thr/Thr
| 49 (12.2) | 60 (13.8) | 1.00 (reference) | ||
+/+
|
Thr/Thr
| 36 (8.9) | 31 (7.1) | 1.22 [0.61–2.43] | 0.578 | |
+/+
|
Thr/Met
| 34 (8.4) | 27 (6.2) | 1.41 [0.68–2.92] | 0.351 | |
+/+
|
Met/Met
|
12 (3.0)
|
6 (1.4)
|
3.06 [0.91–10.30]
| 0.071 | 0.174 |
XPD Lys751Gln | XRCC3 Thr241Met | |||||
Lys/Lys
|
Thr/Thr
| 83 (20.6) | 89 (20.5) | 1.00 (reference) | ||
Gln/Gln
|
Thr/Thr
| 17 (4.2) | 17 (3.9) | 0.98 [0.41–2.35] | 0.968 | |
Gln/Gln
|
Thr/Met
| 20 (5.0) | 18 (4.1) | 1.59 [0.70–3.59] | 0.264 | |
Gln/Gln
|
Met/Met
|
10 (2.5)
|
5 (1.2)
|
2.66 [0.74–9.62]
| 0.135 | 0.261 |