The purpose of the current study is to explore the contribution of single-nucleotide polymorphisms (SNPs) of
Lung cancer is a common malignancy and the most frequent reason of malignancy-associated death worldwide; additionally, approximately 1.8 million new lung cancer patients were diagnosed in 2012, accounting for approximately 13% of total malignancy diagnoses [
Lung cancer is caused by a variety of factors. Single-nucleotide polymorphisms (SNPs) play fundamental roles in tumorigenesis, cancer development, and prognosis. SNPs can modify gene product sequences, regulate gene expression, and influence gene function to change the phenotype.
The pluripotency and self-renewal characteristics of embryonic cells involved multiple levels of cells and a variety of factors, and the coding of stem cell signaling molecules in the genetic polymorphism may be involved in cancer occurrence [
The whole genome sequence analysis and functional experiments showed that the most prominent synergistic factor in the transcriptional repression complex was NuRD, and CTBP is an important ligand for the transcriptional inhibition of NuRD [
1121 newly diagnosed (enrolled in the study at the time of cancer diagnosis) primary lung cancer patients were recruited from three hospitals of the First Clinical Medical College of Fujian Medical University, Fuzhou General Hospital, and the Affiliated Union Hospital of Fujian Medical University, from July 2006 to February 2013. The control group consisted of 1121 age-matched (±2 years) cancer-free individuals recruited from medical examination centers or hospital nononcology departments during the same period. All subjects were Chinese Han who were living in Fujian for >10 years and were able to answer questions clearly. The response rate for subjects was 92.68%. This study was approved by the Institutional Review Board of Fujian Medical University (Fuzhou, China), and all participants signed the informed consent forms.
A unified standard questionnaire according to the principle of informed consent was used. The investigators accepted a unified training for the face-to-face interview survey. The survey includes the general situation (age, gender, ethnicity, education, marital status, height, weight, etc.), living environment, diet history, alcohol drinking history, smoking history, tea drinking history, lung disease history, family history of cancer, and history of physical activity.
The education degree was divided into three levels: primary school or below, junior and senior high school, and college degree or above. The marital status included three grades: married, others (divorced and widowed), and single. We calculated the body mass index (BMI) as body weight (kg)/height2 (m2). House types included bungalow, building, and others. There were three different ventilation situations, well, general, or worse, which was judged according to the ventilation of the bedroom. To evaluate cooking oil fume (COF) exposure, the fumes in the kitchen during cooking were classified into no fumes, little fumes, some fumes, or much fumes. Redecoration within 10 years, smoking, passive smoking, tea drinking, history of lung disease, and family history of cancer were provided with a binary response (“no” or “yes”). The kitchen ventilator was a machine that sucked cooking oil fumes out of the kitchens. Redecoration within 10 years indicated that the interior had been redecorated or painted within the last 10 years. Smoking status was defined as individuals who had smoked at least 100 cigarettes during their lifetime. Passive smoking was defined as exposure to other environmental sources of tobacco smoke at home and/or at work for more than 15 minutes per day. Drinking alcohol was defined as drinking at least once per week for more than half a year. Tea drinkers were defined as those who consumed at least 1 cup of tea per day, for at least 6 consecutive months. History of lung disease referred to a history of chronic bronchitis, emphysema, tuberculosis, and other chronic respiratory diseases. Family history of cancer was any type of cancer in any immediate family member.
Peripheral blood samples were obtained from both patients and control subjects included in this study and stored in EDTA tubes. Protease K digestion and phenol-chloroform extraction were used to extract the genomic DNA from blood samples. The purified genomic DNA was stored at -20°C until being used for SNP genotyping.
Genotyping [
The genomic DNA was used for SNP genotyping with the Sequenom platform in accordance with the manufacturer’s iPLEX Application Guide (Sequenom Inc., San Diego, CA). The samples were scanned using a matrix-assisted laser desorption ionization-time of flight mass spectrometry system and genotyped with a MassARRAY Typer 3.4 (Sequenom Inc., San Diego, CA). For quality control, approximately 10% of randomly selected samples were rerun. The concordance rate was 99.5%, and the genotyping call rates reached >90%.
IBM SPSS 21.0 software (Armonk, NY, USA) was used, and the statistical significance was set to 0.05. Demographic features between lung cancer patients and healthy controls were compared by a 2-sided chi-squared test to identify the potential differences. An online calculator with
Our study was approved by the Ethical Committee of Fujian Medical University (Fuzhou, China) ([2014] Fu Yi Ethics Review (No. 98)), and all participants signed the informed consent forms.
The demographic characteristics of 1121 patients and 1121 controls are listed in Table
Demographic characteristics of the included patients and healthy control.
Variable | Case group (%) | Control group (%) | OR (95% CI) |
---|---|---|---|
Age | |||
≤52 | 295 (26.3) | 289 (25.8) | 1.000 |
53-59 | 285 (25.4) | 273 (24.4) | 1.012 (0.802-1.278) |
60-66 | 272 (24.3) | 274 (24.4) | 0.973 (0.770-1.228) |
≥67 | 269 (24.0) | 285 (25.4) | 0.925 (0.733-1.167) |
Gender | |||
Male | 797 (71.1) | 797 (71.1) | 1.000 |
Female | 324 (28.9) | 324 (28.9) | 1.000 (0.833-1.200) |
Degree of education | |||
Primary school or below | 564 (50.4) | 418 (37.3) | 1.000 |
Junior and senior high school | 443 (39.6) | 553 (49.3) | |
College degree or above | 114 (10.2) | 150 (13.4) | |
Marital status | |||
Married | 1054 (94.0) | 1039 (92.7) | 1.000 |
Others | 64 (5.7) | 66 (5.9) | 0.956 (0.671-1.362) |
Single | 3 (0.3) | 16 (1.4) | |
BMI (kg/m2) | |||
<18.5 | 124 (11.1) | 51 (4.5) | 1.000 |
18.5-23.9 | 694 (61.9) | 613 (54.7) | |
≥24 | 303 (27.0) | 457 (40.8) | |
Pollution near the place of residence | |||
Not | 900 (80.3) | 1026 (91.5) | 1.000 |
Exist | 221 (19.7) | 95 (8.5) | |
House type | |||
Bungalow | 377 (33.6) | 182 (16.2) | 1.000 |
Building | 734 (65.5) | 931 (83.1) | |
Others | 10 (0.9) | 8 (0.7) | 0.603 (0.234-1.555) |
Ventilation situation | |||
Well | 859 (76.6) | 990 (88.3) | 1.000 |
General | 223 (19.9) | 115 (10.3) | |
Worse | 39 (3.5) | 16 (1.4) | |
Cooking oil fume (COF) | |||
No | 190 (16.9) | 350 (31.2) | 1.000 |
Little | 613 (54.7) | 544 (48.5) | |
Some | 269 (24.0) | 205 (18.3) | |
Much | 49 (4.4) | 22 (2.0) | |
Kitchen ventilator | |||
No | 480 (42.8) | 337 (30.1) | 1.000 |
Yes | 641 (57.2) | 784 (69.9) | |
Decoration within 10 years | |||
No | 674 (60.1) | 692 (61.7) | 1.000 |
Yes | 447 (39.9) | 429 (38.3) | 1.070 (0.903-1.268) |
Smoking | |||
No | 425 (37.9) | 659 (58.8) | 1.000 |
Yes | 696 (62.1) | 462 (41.2) | |
Passive smoking | |||
No | 335 (29.9) | 621 (55.4) | 1.000 |
Yes | 786 (70.1) | 500 (44.6) | |
Drink alcohol | |||
No | 733 (65.4) | 805 (71.8) | 1.000 |
Yes | 388 (34.6) | 316 (28.2) | |
Drink tea | |||
No | 566 (50.5) | 537 (47.9) | 1.000 |
Yes | 555 (49.5) | 584 (52.1) | 0.902 (0.764-1.064) |
History of lung disease | |||
No | 983 (87.7) | 1025 (91.4) | 1.000 |
Yes | 138 (12.3) | 96 (8.6) | |
Family history of cancer | |||
No | 900 (80.3) | 950 (84.7) | 1.000 |
Yes | 221 (19.7) | 171 (15.3) |
BMI = weight (kg)/height2 (m2).
The results of unconditional logistic regression analysis showed that there was no association between
Association of rs13409 SNP with susceptibility to lung cancer.
Genotyping | Case (%) | Control (%) | OR (95% CI) | a(OR (95% CI)# | |
---|---|---|---|---|---|
Codominant | CC | 512 (50.1) | 466 (44.3) | 1.000 | 1.000 |
CT | 389 (38.1) | 478 (45.4) | 0.741 (0.617-0.890) | ||
TT | 121 (11.8) | 109 (10.3) | 1.010 (0.758-1.347) | 0.908 (0.657-1.257) | |
Dominant | CC | 512 (50.1) | 466 (44.3) | 1.000 | 1.000 |
CT+TT | 510 (49.9) | 587 (55.7) | 0.791 (0.665-0.940) | ||
Recessive | CC+CT | 901 (88.2) | 944 (89.7) | 1.000 | 1.000 |
TT | 121 (11.8) | 109 (10.3) | 1.163 (0.884-1.530) | 1.054 (0.774-1.436) | |
Additive | 0.908 (0.799-1.032) | 0.873 (0.755-1.009) |
#By the degree of education, marital status, BMI, pollution near the place of residence, house type, ventilation situation, COF, kitchen ventilator, smoking, passive smoking, drink alcohol, history of lung disease, and family history of cancer adjusted. OR and its interval shown in italic font to represent
Association of another three SNPs with susceptibility to lung cancer.
Classification | Case (%) | Control (%) | OR (95% CI) | aOR (95% CI)# | |
---|---|---|---|---|---|
rs6815391 | |||||
Codominant | TT | 477 (46.8) | 472 (45.7) | 1.000 | 1.000 |
CT | 438 (42.9) | 435 (42.1) | 0.996 (0.829-1.197) | 0.901 (0.732-1.109) | |
CC | 105 (10.3) | 126 (12.2) | 0.825 (0.618-1.100) | 0.925 (0.670-1.279) | |
Dominant | TT | 477 (46.8) | 472 (45.7) | 1.000 | 1.000 |
CT+CC | 543 (53.2) | 561 (54.3) | 0.958 (0.805-1.139) | 0.906 (0.745-1.102) | |
Recessive | TT+CT | 915 (89.7) | 907 (87.8) | 1.000 | 1.000 |
CC | 105 (10.3) | 126 (12.2) | 0.826 (0.628-1.087) | 0.973 (0.715-1.323) | |
Additive | 0.936 (0.823-1.065) | 0.942 (0.814-1.089) | |||
rs3740535 | |||||
Codominant | GG | 602 (57.4) | 614 (56.9) | 1.000 | 1.000 |
AG | 373 (35.6) | 401 (37.1) | 0.949 (0.792-1.136) | 0.916 (0.747-1.124) | |
AA | 73 (7.0) | 64 (6.0) | 1.163 (0.817-1.657) | 1.067 (0.714-1.594) | |
Dominant | GG | 602 (57.4) | 614 (56.9) | 1.000 | 1.000 |
AG+AA | 446 (42.6) | 465 (43.1) | 0.978 (0.824-1.162) | 0.937 (0.772-1.139) | |
Recessive | AG+GG | 975 (93.0) | 1015 (94.0) | 1.000 | 1.000 |
AA | 73 (7.0) | 64 (6.0) | 1.187 (0.839-1.680) | 1.103 (0.744-1.636) | |
Additive | 1.013 (0.882-1.163) | 0.974 (0.833-1.139) | |||
rs3130932 | |||||
Codominant | TT | 453 (43.4) | 453 (41.8) | 1.000 | 1.000 |
GT | 460 (44.0) | 494 (45.7) | 0.931 (0.776-1.117) | 0.890 (0.725-1.093) | |
GG | 132 (12.6) | 135 (12.5) | 0.978 (0.744-1.285) | 1.031 (0.757-1.404) | |
Dominant | TT | 453 (43.4) | 453 (41.8) | 1.000 | 1.000 |
GT+GG | 592 (56.6) | 629 (58.2) | 0.941 (0.793-1.118) | 0.919 (0.757-1.116) | |
Recessive | GT+TT | 913 (87.4) | 947 (87.5) | 1.000 | 1.000 |
GG | 132 (12.6) | 135 (12.5) | 1.014 (0.785-1.311) | 1.095 (0.819-1.463) | |
Additive | 0.972 (0.857-1.101) | 0.977 (0.848-1.125) |
#By the degree of education, marital status, BMI, pollution near the place of residence, house type, ventilation situation, COF, kitchen ventilator, smoking, passive smoking, drink alcohol, history of lung disease, and family history of cancer adjusted.
There was no significant difference between
For the adenocarcinoma patients with
Regarding squamous cell carcinoma, the risk of lung cancer in
Association of the four SNPs of different pathological types with susceptibility to lung cancer.
Lung adenocarcinoma | Lung squamous cell carcinoma | Total | ||||
---|---|---|---|---|---|---|
Classification | Case/control | Case/control | Case/control | |||
rs13409 | ||||||
CC | 252/466 | 1.000 | 147/466 | 1.000 | 490/466 | 1.000 |
CT | 177/478 | 109/478 | 0.756 (0.543-1.053) | 369/478 | ||
TT | 58/109 | 0.987 (0.672-1.450) | 30/109 | 0.754 (0.444-1.282) | 113/109 | 0.986 (0.736-1.320) |
rs13409 | ||||||
CC | 352/466 | 1.000 | 147/466 | 1.000 | 490/466 | 1.000 |
CT+TT | 235/587 | 139/587 | 0.756 (0.553-1.033) | 482/587 | ||
rs13409 | ||||||
CC+CT | 429/944 | 1.000 | 256/944 | 1.000 | 859/944 | 1.000 |
TT | 58/109 | 1.171 (0.811-1.692) | 30/109 | 0.861 (0.518-1.430) | 859/109 | 1.039 (0.862-1.506) |
rs13409 | 0.879 (0.737-1.048) | 0.827 (0.653-1.047) | 0.897 (0.788-1.022) | |||
rs6815391 | ||||||
TT | 230/472 | 1.000 | 136/472 | 1.000 | 452/472 | 1.000 |
CT | 205/435 | 0.905 (0.705-1.161) | 125/435 | 1.028 (0.740-1.428) | 418/435 | 1.003 (0.833-1.209) |
CC | 49/126 | 0.836 (0.562-1.241) | 26/126 | 0.830 (0.482-1.429) | 101/126 | 0.837 (0.625-1.121) |
rs6815391 | ||||||
TT | 230/472 | 1.000 | 136/472 | 1.000 | 452/472 | 1.000 |
CT+CC | 254/561 | 0.890 (0.703-1.126) | 151/561 | 0.986 (0.722-1.348) | 519/561 | 0.966 (0.810-1.152) |
rs6815391 | ||||||
TT+CT | 435/907 | 1.000 | 261/907 | 1.000 | 870/907 | 1.000 |
CC | 49/126 | 0.876 (0.600-1.278) | 26/126 | 0.819 (0.488-1.377) | 101/126 | 0.836 (0.633-1.103) |
rs6815391 | 0.911 (0.764-1.086) | 0.952 (0.752-1.204) | 0.943 (0.828-1.074) | |||
rs3740535 | ||||||
GG | 295/614 | 1.000 | 159/614 | 1.000 | 571/614 | 1.000 |
AG | 169/401 | 0.875 (0.683-1.123) | 114/401 | 1.034 (0.748-1.430) | 354/401 | 0.949 (0.791-1.140) |
AA | 35/64 | 0.968 (0.598-1.567) | 19/64 | 1.243 (0.650-2.375) | 72/64 | 1.210 (0.848-1.726) |
rs3740535 | ||||||
GG | 295/614 | 1.000 | 159/614 | 1.000 | 571/614 | 1.000 |
GA+AA | 204/465 | 0.889 (0.702-1.126) | 133/465 | 1.061 (0.778-1.447) | 426/465 | 0.985 (0.828-1.172) |
rs3740535 | ||||||
GA+GG | 464/1015 | 1.000 | 273/1015 | 1.000 | 925/1015 | 1.000 |
AA | 35/64 | 1.018 (0.634-1.632) | 19/64 | 1.226 (0.650-2.314) | 72/64 | 1.234 (0.871-1.749) |
rs3740535 | 0.930 (0.769-1.124) | 1.073 (0.834-1.381) | 1.024 (0.891-1.178) | |||
rs3130932 | ||||||
TT | 228/453 | 1.000 | 119/453 | 1.000 | 432/453 | 1.000 |
GT | 213/494 | 0.786 (0.613-1.008) | 124/494 | 1.030 (0.737-1.440) | 438/494 | 0.930 (0.773-1.118) |
GG | 57/135 | 0.893 (0.611-1.307) | 46/135 | 1.593 (0.999-2.541) | 125/135 | 0.971 (0.736-1.280) |
rs3130932 | ||||||
TT | 228/453 | 1.000 | 119/453 | 1.000 | 432/453 | 1.000 |
GT+GG | 270/629 | 0.807 (0.639-1.021) | 170/629 | 1.146 (0.838-1.567) | 563/629 | 0.939 (0.789-1.117) |
rs3130932 | ||||||
GT+TT | 441/947 | 1.000 | 243/947 | 1.000 | 870/947 | 1.000 |
GG | 57/135 | 1.009 (0.705-1.446) | 46/135 | 125/135 | 1.008 (0.777-1.307) | |
rs3130932 | 0.894 (0.752-1.064) | 1.201 (0.961-1.501) | 0.969 (0.853-1.100) |
#By the degree of education, marital status, BMI, pollution near the place of residence, house type, ventilation situation, COF, kitchen ventilator, smoking, passive smoking, drink alcohol, history of lung disease, and family history of cancer adjusted. OR and its interval shown in italic font to represent the
We analyzed the interactions between the four genotypes and the environment factors including pollution near the place of residence, house type, COF, ventilation situation, kitchen ventilator, smoking, passive smoking, drink alcohol, history of lung disease, and family history of cancer (Tables
Joint and multiplication interaction between gene dominant model and environmental factors.
Genotype | Environment | Case (%) | Control (%) | OR (95% CI) | aOR (95% CI)# |
---|---|---|---|---|---|
rs13409 | |||||
rs13409 with pollution near the place of residence | |||||
CC | No | 414 (40.5) | 429 (40.7) | 1.000 | 1.000 |
CC | Yes | 98 (9.6) | 37 (3.5) | 2.745 (1.837-4.101) | |
CT+TT | No | 410 (40.1) | 540 (51.3) | 0.787 (0.653-0.948) | |
CT+TT | Yes | 100 (9.8) | 47 (4.5) | 2.205 (1.520-3.198) | |
rs13409 × pollution near the place of residence | ORmultiply (95% CI) | 2.322 (1.623-3.321) | |||
rs13409 with house type | |||||
CC | No | 174 (17.0) | 80 (7.6) | 1.000 | 1.000 |
CC | Yes | 338 (33.1) | 386 (36.7) | 0.403 (0.298-0.545) | |
CT+TT | No | 174 (17.0) | 93 (8.8) | 0.860 (0.597-1.240) | 0.761 (0.510-1.136) |
CT+TT | Yes | 336 (32.9) | 494 (46.9) | 0.313 (0.232-0.422) | |
rs13409 × house type | ORmultiply (95% CI) | 0.554 (0.464-0.662) | |||
rs13409 with ventilation situation | |||||
CC | No | 17 (1.7) | 8 (0.8) | 1.000 | 1.000 |
CC | Yes | 495 (48.4) | 458 (43.5) | 0.509 (0.217-1.190) | 0.654 (0.257-1.665) |
CT+TT | No | 19 (1.9) | 7 (0.7) | 1.277 (0.382-4.271) | 1.305 (0.350-4.862) |
CT+TT | Yes | 491 (48.0) | 580 (55.1) | 0.398 (0.170-1.931) | 0.497 (0.196-1.264) |
rs13409 × ventilation situation | ORmultiply (95% CI) | 0.754 (0.635-0.896) | |||
rs13409 with kitchen ventilator | |||||
CC | No | 215 (21.0) | 138 (13.1) | 1.000 | 1.000 |
CC | Yes | 297 (29.1) | 328 (31.1) | 0.581 (0.446-0.758) | 0.973 (0.712-1.330) |
CT+TT | No | 224 (21.9) | 177 (16.8) | 0.812 (0.607-1.086) | 0.808 (0.583-1.120) |
CT+TT | Yes | 286 (28.0) | 410 (38.9) | 0.448 (0.345-0.582) | |
rs13409 × kitchen ventilator | ORmultiply (95% CI) | 0.609 (0.507-0.733) | |||
rs13409 with COF | |||||
CC | No | 84 (8.2) | 153 (14.5) | 1.000 | 1.000 |
CC | Yes | 428 (41.9) | 313 (29.7) | 2.491 (1.839-3.374) | |
CT+TT | No | 88 (8.6) | 182 (17.3) | 0.881 (0.609-1.273) | 0.855 (0.569-1.286) |
CT+TT | Yes | 422 (41.3) | 405 (38.5) | 1.898 (1.407-2.559) | |
rs13409 × COF | ORmultiply (95% CI) | 1.125 (0.944-1.342) | |||
rs13409 with smoking | |||||
CC | No | 202 (19.8) | 264 (25.1) | 1.000 | 1.000 |
CC | Yes | 310 (30.3) | 202 (19.2) | 2.006 (1.554-2.588) | |
CT+TT | No | 189 (18.5) | 361 (34.3) | 0.684 (0.531-0.882) | |
CT+TT | Yes | 321 (31.4) | 226 (21.5) | 1.856 (1.446-2.384) | |
rs13409 × smoking | ORmultiply (95% CI) | 1.676 (1375-2.042) | |||
rs13409 with passive smoking | |||||
CC | No | 156 (15.3) | 267 (25.4) | 1.000 | 1.000 |
CC | Yes | 356 (34.8) | 199 (18.9) | 3.062 (2.354-3.982) | |
CT+TT | No | 151 (14.8) | 317 (30.1) | 0.815 (0.618-1.075) | 0.766 (0.567-1.037) |
CT+TT | Yes | 359 (35.1) | 270 (25.6) | 2.276 (1.767-2.930) | |
rs13409 × passive smoking | ORmultiply (95% CI) | 1.570 (1.300-1.897) | |||
rs13409 with drink alcohol | |||||
CC | No | 343 (33.6) | 329 (31.2) | 1.000 | 1.000 |
CC | Yes | 169 (16.5) | 137 (13.0) | 1.183 (0.902-1.552) | 0.800 (0.581-1.100) |
CT+TT | No | 328 (32.1) | 421 (40.0) | 0.747 (0.606-0.921) | |
CT+TT | Yes | 182 (17.8) | 166 (15.8) | 1.052 (0.812-1.363) | |
rs13409 × drink alcohol | ORmultiply (95% CI) | 1.158 (0.919-1.458) | 0.793 (0.608-1.034) | ||
rs13409 with history of lung disease | |||||
CC | No | 452 (44.2) | 422 (40.1) | 1.000 | 1.000 |
CC | Yes | 60 (5.9) | 44 (4.2) | 1.273 (0.844-1.920) | 1.087 (0.680-1.737) |
CT+TT | No | 442 (43.2) | 542 (51.5) | 0.761 (0.634-0.914) | |
CT+TT | Yes | 68 (6.7) | 45 (4.3) | 1.411 (0.946-2.103) | 1.364 (0.866-2.147) |
rs13409 × history of lung disease | ORmultiply (95% CI) | 1.597 (1.084-2.351) | |||
rs13409 with family history of cancer | |||||
CC | No | 403 (39.4) | 395 (37.5) | 1.000 | 1.000 |
CC | Yes | 109 (10.7) | 71 (6.7) | 1.505 (1.082-2.092) | 1.495 (1.032-2.167) |
CT+TT | No | 412 (40.3) | 501 (47.6) | 0.806 (0.666-0.975) | |
CT+TT | Yes | 98 (9.6) | 86 (8.2) | 1.117 (0.810-1.540) | 1.116 (0.777-1.603) |
rs13409 × family history of cancer | 1.193 (0.881-1.615) | 1.218 (0.865-1.714) | |||
rs6815391 | |||||
rs6815391 with pollution near the place of residence | |||||
TT | No | 385 (37.7) | 425 (41.1) | 1.000 | 1.000 |
TT | Yes | 92 (9.0) | 47 (4.5) | 2.161 (1.481-3.152) | |
CT+CC | No | 436 (42.7) | 522 (50.5) | 0.922 (0.764-1.112) | 0.862 (0.699-1.064) |
CT+CC | Yes | 107 (10.5) | 39 (3.8) | 3.029 (2.047-4.481) | |
rs6815391 × pollution near the place of residence | ORmultiply (95% CI) | 2.987 (2.048-4.357) | |||
rs6815391 with house type | |||||
TT | No | 140 (13.7) | 73 (7.1) | 1.000 | 1.000 |
TT | Yes | 337 (33.0) | 399 (38.6) | 0.440 (0.320-0.605) | |
CT+CC | No | 194 (19.0) | 92 (8.9) | 1.100 (0.755-1.602) | 1.212 (0.802-1.832) |
CT+CC | Yes | 349 (34.2) | 469 (45.4) | 0.388 (0.283-0.532) | |
rs6815391 × house type | ORmultiply (95% CI) | 0.625 (0.523-0.747) | |||
rs6815391 with ventilation situation | |||||
TT | No | 15 (1.5) | 9 (0.9) | 1.000 | 1.000 |
TT | Yes | 462 (45.3) | 463 (44.8) | 0.599 (0.259-1.382) | 0.668 (0.268-1.667) |
CT+CC | No | 23 (2.3) | 6 (0.6) | 2.300 (0.679-7.796) | 1.831 (0.481-6.966) |
CT+CC | Yes | 520 (51.0) | 555 (53.7) | 0.562 (0.244-1.296) | 0.599 (0.241-1.493) |
rs6815391 × ventilation situation | ORmultiply (95% CI) | 0.896 (0.753-1.065) | |||
rs6815391 with kitchen ventilator | |||||
TT | No | 209 (20.5) | 143 (13.8) | 1.000 | 1.000 |
TT | Yes | 268 (26.3) | 329 (31.8) | 0.557 (0.427-0.728) | 0.866 (0.632-1.187) |
CT+CC | No | 226 (22.2) | 164 (15.9) | 0.943 (0.704-1.263) | 0.834 (0.602-1.156) |
CT+CC | Yes | 317 (31.1) | 397 (38.4) | 0.546 (0.422-0.708) | 0.823 (0.607-1.114) |
rs6815391 × kitchen ventilator | ORmultiply (95% CI) | 0.722 (0.602-0.867) | 0.927 (0.752-1.144) | ||
rs6815391 with COF | |||||
TT | No | 89 (8.7) | 158 (15.3) | 1.000 | 1.000 |
TT | Yes | 388 (38.0) | 314 (30.4) | 2.194 (1.626-2.959) | |
CT+CC | No | 86 (8.4) | 179 (17.3) | 0.853 (0.592-1.229) | 0.812 (0.542-1.216) |
CT+CC | Yes | 457 (44.8) | 382 (37.0) | 2.124 (1.584-2.847) | |
rs6815391 × COF | ORmultiply (95% CI) | 1.383 (1.159-1.651) | |||
rs6815391 with smoking | |||||
TT | No | 192 (18.8) | 265 (25.7) | 1.000 | 1.000 |
TT | Yes | 285 (27.9) | 207 (20.0) | 1.900 (1.468-2.460) | |
CT+CC | No | 196 (19.2) | 353 (34.2) | 0.766 (0.594-0.989) | |
CT+CC | Yes | 347 (34.0) | 208 (20.1) | 2.303 (1.788-2.966) | |
rs6815391 × smoking | ORmultiply (95% CI) | 2.045 (1.675-2.497) | |||
rs6815391 with passive smoking | |||||
TT | No | 138 (13.5) | 258 (25.0) | 1.000 | 1.000 |
TT | Yes | 339 (33.2) | 214 (20.7) | 2.962 (2.265-3.873) | |
CT+CC | No | 173 (17.0) | 316 (30.6) | 1.024 (0.755-1.351) | 0.941 (0.695-1.274) |
CT+CC | Yes | 370 (36.3) | 245 (23.7) | 2.823 (2.172-3.670) | |
rs6815391 × passive smoking | ORmultiply (95% CI) | 1.831 (1.511-2.218) | |||
rs6815391 with drinking alcohol | |||||
TT | No | 318 (31.2) | 330 (31.9) | 1.000 | 1.000 |
TT | Yes | 159 (15.6) | 142 (13.7) | 1.162 (0.884-1.528) | 0.728 (0.529-1.003) |
CT+CC | No | 356 (34.9) | 419 (40.6) | 0.882 (0.715-1.087) | 0.817 (0.645-1.034) |
CT+CC | Yes | 187 (18.3) | 142 (13.7) | 1.367 (1.046-1.785) | 0.831 (0.608-1.137) |
rs6815391 × drink alcohol | ORmultiply (95% CI) | 1.409 (1.111-1.787) | 0.978 (0.743-1.287) | ||
rs6815391 with history of lung disease | |||||
TT | No | 419 (41.1) | 436 (42.2) | 1.000 | 1.000 |
TT | Yes | 58 (5.7) | 36 (3.5) | 1.676 (1.083-2.595) | 1.401 (0.851-2.306) |
CT+CC | No | 477 (46.8) | 520 (50.3) | 0.955 (0.795-1.146) | 0.888 (0.723-1.090) |
CT+CC | Yes | 66 (6.5) | 41 (4.0) | 1.675 (1.109-2.529) | 1.560 (0.977-2.490) |
rs6815391× history of lung disease | ORmultiply (95% CI) | 1.674 (1.122-2.496) | |||
rs6815391 with family history of cancer | |||||
TT | No | 385 (37.7) | 400 (38.7) | 1.000 | 1.000 |
TT | Yes | 92 (9.0) | 72 (7.0) | 1.328 (0.946-1.863) | 1.350 (0.923-1.975) |
CT+CC | No | 433 (42.5) | 476 (46.1) | 0.945 (0.781-1.144) | 0.887 (0.715-1.101) |
CT+CC | Yes | 110 (10.8) | 85 (8.2) | 1.345 (0.980-1.844) | 1.353 (0.949-1.929) |
rs6815391 × family history of cancer | ORmultiply (95% CI) | 1.348 (1.001-1.815) | |||
rs3740535 | |||||
rs3740535 with pollution near the place of residence | |||||
GG | No | 464 (44.3) | 561 (52.0) | 1.000 | 1.000 |
GG | Yes | 138 (13.2) | 53 (4.9) | 3.148 (2.241-4.422) | |
GA+AA | No | 376 (35.9) | 431 (39.9) | 1.055 (0.877-1.269) | 0.971 (0.789-1.194) |
GA+AA | Yes | 70 (6.7) | 34 (3.2) | 2.489 (1.623-3.818) | |
rs3740535 × pollution near the place of residence | ORmultiply (95% CI) | 2.200 (1.447-3.344) | |||
rs3740535 with house type | |||||
GG | No | 204 (19.5) | 85 (7.9) | 1.000 | 1.000 |
GG | Yes | 398 (38.0) | 529 (49.0) | 0.313 (0.236-0.417) | |
GA+AA | No | 151 (14.4) | 93 (8.6) | 0.677 (0.471-0.971) | |
GA+AA | Yes | 295 (28.1) | 372 (34.5) | 0.330 (0.246-0.444) | |
rs3740535 × house type | ORmultiply (95% CI) | 0.745 (0.619-0.895) | 0.845 (0.686-1.040) | ||
rs3740535 with ventilation situation | |||||
GG | No | 21 (2.0) | 10 (0.9) | 1.000 | 1.000 |
GG | Yes | 581 (55.4) | 604 (56.0) | 0.458 (0.214-0.981) | 0.529 (0.227-1.228) |
GA+AA | No | 18 (1.7) | 6 (0.6) | 1.429 (0.434-4.705) | 1.127 (0.309-4.108) |
GA+AA | Yes | 428 (40.8) | 459 (42.5) | 0.444 (0.207-0.954) | 0.490 (0.210-1.144) |
rs3740535 × ventilation situation | ORmultiply (95% CI) | 0.932 (0.785-1.108) | |||
rs3740535 with kitchen ventilator | |||||
GG | No | 249 (23.8) | 162 (15.0) | 1.000 | 1.000 |
GG | Yes | 353 (33.7) | 452 (41.9) | 0.508 (0.399-0.647) | 0.809 (0.608-1.076) |
GA+AA | No | 201 (19.2) | 162 (15.0) | 0.807 (0.606-1.075) | 0.758 (0.550-1.045) |
GA+AA | Yes | 245 (23.4) | 303 (28.1) | 0.526 (0.406-0.682) | 0.858 (0.632-1.164) |
rs3740535 × kitchen ventilator | ORmultiply (95% CI) | 0.781 (0.643-0.950) | 1.024 (0.819-1.281) | ||
rs3740535 with COF | |||||
GG | No | 103 (9.8) | 211 (19.6) | 1.000 | 1.000 |
GG | Yes | 499 (47.6) | 403 (37.3) | 2.537 (1.937-3.322) | |
GA+AA | No | 77 (7.3) | 131 (12.1) | 1.204 (0.834-1.738) | 1.272 (0.846-1.911) |
GA+AA | Yes | 369 (35.2) | 334 (31.0) | 2.263 (1.714-2.989) | |
rs3740535 × COF | ORmultiply (95% CI) | 1.212 (1.012-1.453) | 0.965 (0.907-1.027) | ||
rs3740535 with smoking | |||||
GG | No | 246 (23.5) | 361 (33.5) | 1.000 | 1.000 |
GG | Yes | 356 (34.0) | 253 (23.4) | 2.065 (1.643-2.595) | |
GA+AA | No | 154 (14.7) | 274 (25.4) | 0.825 (0.639-1.065) | 0.806 (0.608-1.069) |
GA+AA | Yes | 292 (27.9) | 191 (17.7) | 2.243 (1.758-2.863) | |
rs3740535 × smoking | ORmultiply (95% CI) | 1.796 (1.461-2.208) | |||
rs3740535 with passive smoking | |||||
GG | No | 179 (17.1) | 350 (32.4) | 1.000 | 1.000 |
GG | Yes | 423 (40.4) | 264 (24.5) | 3.133 (2.472-3.970) | |
GA+AA | No | 131 (12.5) | 245 (22.7) | 1.045 (0.792-1.381) | 1.085 (0.801-1.470) |
GA+AA | Yes | 315 (30.1) | 220 (20.4) | 2.800 (2.182-3.592) | |
rs3740535 × passive smoking | ORmultiply (95% CI) | 1.678 (1.376-2.046) | |||
rs3740535 with drink alcohol | |||||
GG | No | 392 (37.4) | 450 (41.7) | 1.000 | 1.000 |
GG | Yes | 210 (20.0) | 164 (15.2) | 1.470 (1.150-1.878) | 0.966 (0.725-1.288) |
GA+AA | No | 292 (27.9) | 320 (29.7) | 1.048 (0.850-1.290) | 1.003 (0.792-1.270) |
GA+AA | Yes | 154 (14.7) | 145 (13.4) | 1.219 (0.936-1.588) | 0.787 (0.578-1.071) |
rs3740535 × drink alcohol | ORmultiply (95% CI) | 1.110 (0.869-1.417) | 0.794 (0.599-1.053) | ||
rs3740535 with history of lung disease | |||||
GG | No | 528 (50.4) | 564 (52.3) | 1.000 | 1.000 |
GG | Yes | 74 (7.1) | 50 (4.6) | 1.581 (1.083-2.307) | |
GA+AA | No | 395 (37.7) | 426 (39.5) | 0.990 (0.826-1.187) | 0.966 (0.787-1.186) |
GA+AA | Yes | 51 (4.9) | 39 (3.6) | 1.397 (0.906-2.155) | 1.129 (0.693-1.837) |
rs3740535× history of lung disease | ORmultiply (95% CI) | 1.364 (0.891-2.088) | 1.110 (0.688-1.790) | ||
rs3740535 with family history of cancer | |||||
GG | No | 485 (46.3) | 524 (48.6) | 1.000 | 1.000 |
GG | Yes | 117 (11.2) | 90 (8.3) | 1.405 (1.039-1.898) | 1.388 (0.989-1.949) |
GA+AA | No | 352 (33.6) | 395 (36.6) | 0.963 (0.797-1.164) | 0.908 (0.733-1.124) |
GA+AA | Yes | 94 (9.0) | 70 (6.5) | 1.451 (1.040-2.024) | |
rs3740535 × family history of cancer | ORmultiply (95% CI) | 1.420 (1.029-1.959) | |||
rs3130932 | |||||
rs3130932 with pollution near the place of residence | |||||
TT | No | 362 (34.6) | 418 (38.6) | 1.000 | 1.000 |
TT | Yes | 91 (8.7) | 35 (3.2) | 3.002 (1.984-4.544) | |
GT+GG | No | 476 (45.6) | 578 (53.4) | 0.951 (0.790-1.145) | 0.937 (0.762-1.153) |
GT+GG | Yes | 116 (11.1) | 51 (4.7) | 2.626 (1.836-3.757) | |
rs3130932 × pollution near the place of residence | ORmultiply (95% CI) | 2.524 (1.795-3.550) | |||
rs3130932 with house type | |||||
TT | No | 149 (14.3) | 75 (6.9) | 1.000 | 1.000 |
TT | Yes | 304 (29.1) | 378 (34.9) | 0.405 (0.295-0.555) | |
GT+GG | No | 207 (19.8) | 103 (9.5) | 1.012 (0.703-1.456) | 1.099 (0.737-1.638) |
GT+GG | Yes | 385 (36.8) | 526 (48.6) | 0.368 (0.271-0.501) | |
rs3130932 × house type | ORmultiply (95% CI) | 0.617 (0.519-0.733) | |||
rs3130932 with ventilation situation | |||||
TT | No | 14 (1.3) | 7 (0.6) | 1.000 | 1.000 |
TT | Yes | 439 (42.0) | 446 (41.2) | 0.492 (0.197-1.231) | 0.516 (0.190-1.402) |
GT+GG | No | 24 (2.3) | 8 (0.7) | 1.500 (0.447-5.029) | 1.086 (0.292-4.045) |
GT+GG | Yes | 568 (54.4) | 621 (57.4) | 0.457 (0.183-1.141) | 0.473 (0.174-1.282) |
rs3130932 × ventilation situation | ORmultiply (95% CI) | 0.884 (0.745-1.049) | |||
rs3130932 with kitchen ventilator | |||||
TT | No | 204 (19.5) | 147 (13.6) | 1.000 | 1.000 |
TT | Yes | 249 (23.8) | 306 (28.3) | 0.586 (0.448-0.768) | 1.036 (0.752-1.427) |
GT+GG | No | 246 (23.5) | 179 (16.5) | 0.990 (0.744-1.319) | 1.025 (0.744-1.411) |
GT+GG | Yes | 346 (33.1) | 450 (41.6) | 0.554 (0.430-0.714) | 0.894 (0.662-1.207) |
rs3130932 × kitchen ventilator | ORmultiply (95% CI) | 0.695 (0.583-0.830) | 0.872 (0.711-1.070) | ||
rs3130932 with COF | |||||
TT | No | 85 (8.1) | 150 (13.9) | 1.000 | 1.000 |
TT | Yes | 368 (35.2) | 303 (28.0) | 2.143 (1.578-2.912) | |
GT+GG | No | 96 (9.2) | 191 (17.7) | 0.887 (0.618-1.274) | 0.849 (0.568-1.268) |
GT+GG | Yes | 496 (47.5) | 438 (40.5) | 1.998 (1.487-2.685) | |
rs3130932 × COF | ORmultiply (95% CI) | 1.328 (1.119-1.577) | 0.951 (0.895-1.011) | ||
rs3130932 with smoking | |||||
TT | No | 170 (16.3) | 268 (24.8) | 1.000 | 1.000 |
TT | Yes | 283 (27.1) | 185 (17.1) | 2.412 (1.847-3.149) | |
GT+GG | No | 223 (21.3) | 370 (34.2) | 0.950 (0.737-1.225) | 0.929 (0.702-1.229) |
GT+GG | Yes | 369 (35.3) | 259 (23.9) | 2.246 (1.750-2.882) | |
rs3130932 × smoking | ORmultiply (95% CI) | 1.735 (1.436-2.095) | |||
rs3130932 with passive smoking | |||||
TT | No | 133 (12.7) | 260 (24.0) | 1.000 | 1.000 |
TT | Yes | 320 (30.6) | 193 (17.8) | 3.241 (2.467-4.267) | |
GT+GG | No | 178 (17.0) | 340 (31.4) | 1.023 (0.776-1.350) | 1.006 (0.744-1.361) |
GT+GG | Yes | 414 (39.6) | 289 (26.7) | 2.800 (2.165-3.622) | |
rs3130932 × passive smoking | ORmultiply (95% CI) | 1.800 (1.499-2.162) | |||
rs3130932 with drink alcohol | |||||
TT | No | 296 (28.3) | 325 (30.0) | 1.000 | 1.000 |
TT | Yes | 157 (15.0) | 128 (11.8) | 1.347 (1.016-1.785) | 0.861 (0.621-1.194) |
GT+GG | No | 385 (36.8) | 449 (41.5) | 0.941 (0.765-1.159) | 0.910 (0.719-1.152) |
GT+GG | Yes | 207 (19.8) | 180 (16.6) | 1.263 (0.979-1.628) | 0.808 (0.598-1.091) |
rs3130932 × drink alcohol | ORmultiply (95% CI) | 1.238 (0.993-1.544) | 0.872 (0.674-1.129) | ||
rs3130932 with history of lung disease | |||||
TT | No | 398 (38.1) | 417 (38.5) | 1.000 | 1.000 |
TT | Yes | 55 (5.3) | 36 (3.3) | 1.601 (1.029-2.491) | 1.495 (0.909-2.460) |
GT+GG | No | 524 (50.1) | 575 (53.1) | 0.955 (0.796-1.145) | 0.934 (0.761-1.145) |
GT+GG | Yes | 68 (6.5) | 54 (5.0) | 1.319 (0.900-1.935) | 1.185 (0.762-1.841) |
rs3130932 × history of lung disease | ORmultiply (95% CI) | 1.412 (1.065-1.871) | 1.205 (0.789-1.843) | ||
rs3130932 with family history of cancer | |||||
TT | No | 369 (35.3) | 387 (35.8) | 1.000 | 1.000 |
TT | Yes | 84 (8.0) | 66 (6.1) | 1.335 (0.938-1.899) | 1.267 (0.855-1.878) |
GT+GG | No | 467 (44.7) | 534 (49.4) | 0.917 (0.759-1.108) | 0.877 (0.708-1.085) |
GT+GG | Yes | 125 (12.0) | 95 (8.8) | 1.380 (1.020-1.867) | |
rs3130932 × family history of cancer | ORmultiply (95% CI) | 1.412 (1.065-1.871) |
#By the degree of education, marital status, BMI, pollution near the place of residence, house type, ventilation situation, COF, kitchen ventilator, smoking, passive smoking, drink alcohol, history of lung disease, and family history of cancer adjusted. OR and its interval shown in italic font to represent the
Joint and multiplication interaction between gene recessive model and environmental factors.
Genotype | Environment | Case (%) | Control (%) | OR (95% CI) | aOR (95% CI)# |
---|---|---|---|---|---|
rs13409 | |||||
rs13409 with pollution near the place of residence | |||||
CT+CC | No | 736 (72.0) | 866 (82.2) | 1.000 | 1.000 |
CT+CC | Yes | 165 (16.1) | 78 (7.4) | 2.489 (1.869-3.315) | |
TT | No | 88 (8.6) | 103 (9.8) | 1.005 (0.744-1.358) | 0.909 (0.649-1.272) |
TT | Yes | 33 (3.2) | 6 (0.6) | 6.471 (2.697-15.530) | |
rs13409 × pollution near the place of residence | ORmultiply (95% CI) | 5.823 (2.429-13.956) | |||
rs13409 with house type | |||||
CT+CC | No | 303 (29.6) | 156 (14.8) | 1.000 | 1.000 |
CT+CC | Yes | 598 (58.5) | 788 (74.8) | 0.402 (0.302-0.535) | |
TT | No | 45 (4.4) | 17 (1.6) | 2.600 (1.046-6.463) | |
TT | Yes | 76 (7.4) | 92 (8.7) | 0.404 (0.273-0.598) | |
rs13409 × house type | ORmultiply (95% CI) | 1.009 (0.866-1.175) | 0.846 (0.595-1.203) | ||
rs13409 with ventilation situation | |||||
CT+CC | No | 31 (3.0) | 13 (1.2) | 1.000 | 1.000 |
CT+CC | Yes | 870 (85.1) | 931 (88.4) | 0.392 (0.204-0.754) | 0.509 (0.248-1.045) |
TT | No | 5 (0.5) | 2 (0.2) | 1.048 (0.180-6.112) | 1.311 (0.194-8.848) |
TT | Yes | 116 (11.4) | 107 (10.2) | 0.455 (0.226-0.914) | 0.544 (0.252-1.175) |
rs13409 × ventilation situation | ORmultiply (95% CI) | 1.132 (0.857-1.495) | |||
rs13409 with kitchen ventilator | |||||
CT+CC | No | 381 (37.3) | 275 (26.1) | 1.000 | 1.000 |
CT+CC | Yes | 520 (50.9) | 669 (63.5) | 0.561 (0.463-0.680) | 0.913 (0.718-1.160) |
TT | No | 58 (5.7) | 40 (3.8) | 1.047 (0.680-1.612) | 0.934 (0.577-1.512) |
TT | Yes | 63 (6.2) | 69 (6.6) | 0.659 (0.453-0.959) | 1.046 (0.680-1.608) |
rs13409 × kitchen ventilator | ORmultiply (95% CI) | 0.937 (0.658-1.333) | 1.117 (0.752-1.658) | ||
rs13409 with COF | |||||
CT+CC | No | 149 (14.6) | 311 (29.5) | 1.000 | 1.000 |
CT+CC | Yes | 752 (73.6) | 633 (60.1) | 2.480 (1.986-3.096) | |
TT | No | 23 (2.3) | 24 (2.3) | 2.000 (1.093-3.661) | |
TT | Yes | 98 (9.6) | 85 (8.1) | 2.406 (1.696-3.415) | |
rs13409 × COF | ORmultiply (95% CI) | 1.208 (0.891-1.637) | 1.015 (0.916-1.124) | ||
rs13409 with smoking | |||||
CT+CC | No | 351 (34.3) | 561 (53.3) | 1.000 | 1.000 |
CT+CC | Yes | 550 (53.8) | 383 (36.4) | 2.295 (1.905-2.766) | |
TT | No | 40 (3.9) | 64 (6.1) | 0.999 (0.658-1.516) | 0.935 (0.592-1.477) |
TT | Yes | 81 (7.9) | 45 (4.3) | 2.877 (1.952-4.241) | |
rs13409 × smoking | ORmultiply (95% CI) | 1.928 (1.325-2.086) | 1.515 (0.995-2.307) | ||
rs13409 with passive smoking | |||||
CT+CC | No | 271 (26.5) | 528 (50.1) | 1.000 | 1.000 |
CT+CC | Yes | 630 (61.6) | 416 (39.5) | 2.951 (2.436-3.574) | |
TT | No | 36 (3.5) | 56 (5.3) | 1.253 (0.804-1.925) | 1.111 (0.683-1.807) |
TT | Yes | 85 (8.3) | 53 (5.0) | 3.125 (2.152-4.537) | |
rs13409 × passive smoking | ORmultiply (95% CI) | 1.712 (1.201-2.440) | 1.475 (0.997-2.181) | ||
rs13409 with drink alcohol | |||||
CT+CC | No | 598 (58.5) | 675 (64.1) | 1.000 | 1.000 |
CT+CC | Yes | 303 (29.6) | 269 (25.5) | 1.271 (1.043-1.549) | 0.829 (0.652-1.052) |
TT | No | 73 (7.1) | 75 (7.1) | 1.099 (0.782-1.544) | 0.983 (0.669-1.444) |
TT | Yes | 48 (4.7) | 34 (3.2) | 1.594 (1.013-2.506) | 0.992 (0.594-1.659) |
rs13409 × drink alcohol | ORmultiply (95% CI) | 1.477 (0.944-2.312) | 1.070 (0.647-1.768) | ||
rs13409 with history of lung disease | |||||
CT+CC | No | 793 (77.6) | 859 (81.6) | 1.000 | 1.000 |
CT+CC | Yes | 108 (10.6) | 85 (8.1) | 1.376 (1.019-1.858) | 1.289 (0.915-1.816) |
TT | No | 101 (9.9) | 105 (10.0) | 1.042 (0.780-1.392) | 0.944 (0.682-1.308) |
TT | Yes | 20 (2.0) | 4 (0.4) | 5.416 (1.843-15.914) | |
rs13409 × history of lung disease | ORmultiply (95% CI) | 5.235 (1.783-15.368) | |||
rs13409 with family history of cancer | |||||
CT+CC | No | 714 (69.9) | 805 (76.4) | 1.000 | 1.000 |
CT+CC | Yes | 187 (18.3) | 139 (13.2) | 1.517 (1.191-1.931) | |
TT | No | 101 (9.9) | 91 (8.6) | 1.251 (0.926-1.690) | 1.101 (0.784-1.546) |
TT | Yes | 20 (2.0) | 18 (1.7) | 1.253 (0.657-2.387) | 1.296 (0.632-2.661) |
rs13409 × family history of cancer | ORmultiply (95% CI) | 1.148 (0.604-2.182) | 1.197 (0.584-2.453) | ||
rs6815391 | |||||
rs6815391 with pollution near the place of residence | |||||
TT+CT | No | 733 (71.9) | 832 (80.5) | 1.000 | 1.000 |
TT+CT | Yes | 182 (17.8) | 75 (7.3) | 2.754 (2.068-3.669) | |
CC | No | 88 (8.6) | 115 (11.1) | 0.869 (0.647-1.166) | 1.001 (0.721-1.389) |
CC | Yes | 17 (1.7) | 11 (1.1) | 1.754 (0.816-3.769) | 1.963 (0.855-4.505) |
rs6815391 × pollution near the place of residence | ORmultiply (95% CI) | 1.575 (0.734-3.379) | 1.754 (0.764-4.026) | ||
rs6815391 with house type | |||||
TT+CT | No | 302 (29.6) | 144 (13.9) | 1.000 | 1.000 |
TT+CT | Yes | 613 (60.1) | 763 (73.9) | 0.383 (0.306-0.480) | |
CC | No | 32 (3.1) | 21 (2.0) | 0.727 (0.405-1.304) | 0.844 (0.445-1.602) |
CC | Yes | 73 (7.2) | 105 (10.2) | 0.332 (0.232-0.474) | |
rs6815391 × house type | ORmultiply (95% CI) | 0.681 (0.499-0.931) | 0.875 (0.616-1.243) | ||
rs6815391 with ventilation situation | |||||
TT+CT | No | 36 (3.5) | 13 (1.3) | 1.000 | 1.000 |
TT+CT | Yes | 879 (86.2) | 894 (86.5) | 0.355 (0.187-0.674) | |
CC | No | 2 (0.2) | 2 (0.2) | 0.361 (0.046-2.838) | 0.193 (0.021-1.757) |
CC | Yes | 103 (10.1) | 124 (12.0) | 0.300 (0.151-0.596) | |
rs6815391 × ventilation situation | ORmultiply (95% CI) | 0.823 (0.624-1.086) | 1.031 (0.466-2.281) | ||
rs6815391 with kitchen ventilator | |||||
TT+CT | No | 402 (39.4) | 279 (27.0) | 1.000 | 1.000 |
TT+CT | Yes | 513 (50.3) | 628 (60.8) | 0.567 (0.468-0.687) | 0.910 (0.717-1.155) |
CC | No | 33 (3.2) | 28 (2.7) | 0.818 (0.483-1.384) | 0.860 (0.478-1.547) |
CC | Yes | 72 (7.1) | 98 (9.5) | 0.510 (0.363-0.717) | 0.927 (0.627-1.372) |
rs6815391 × kitchen ventilator | ORmultiply (95% CI) | 0.725 (0.528-0.995) | 0.994 (0.698-1.415) | ||
rs6815391 with COF | |||||
TT+CT | No | 150 (14.7) | 290 (28.1) | 1.000 | 1.000 |
TT+CT | Yes | 765 (75.0) | 617 (59.7) | 2.397 (1.916-2.998) | |
CC | No | 25 (2.5) | 47 (4.5) | 1.028 (0.609-1.736) | 1.080 (0.614-1.900) |
CC | Yes | 80 (7.8) | 79 (7.6) | 1.958 (1.355-2.829) | |
rs6815391 × COF | ORmultiply (95% CI) | 1.028 (0.744-1.421) | 0.960 (0.872-1.057) | ||
rs6815391 with smoking | |||||
TT+CT | No | 349 (34.2) | 536 (51.9) | 1.000 | 1.000 |
TT+CT | Yes | 566 (55.5) | 371 (35.9) | 2.343 (1.942-2.827) | |
CC | No | 39 (3.8) | 82 (7.9) | 0.730 (0.487-1.094) | 0.858 (0.555-1.328) |
CC | Yes | 66 (6.5) | 44 (4.3) | 2.304 (1.537-3.453) | |
rs6815391 × smoking | ORmultiply (95% CI) | 1.555 (1.051-2.301) | 1.531 (0.994-2.359) | ||
rs6815391 with passive smoking | |||||
TT+CT | No | 273 (26.8) | 499 (48.3) | 1.000 | 1.000 |
TT+CT | Yes | 642 (62.9) | 408 (39.5) | 2.876 (2.372-3.488) | |
CC | No | 38 (3.7) | 75 (7.3) | 0.926 (0.610-1.406) | 0.895 (0.569-1.409) |
CC | Yes | 67 (6.6) | 51 (4.9) | 2.401 (1.621-3.557) | |
rs6815391 × passive smoking | ORmultiply (95% CI) | 1.354 (0.930-1.970) | |||
rs6815391 with drink alcohol | |||||
TT+CT | No | 603 (59.1) | 658 (63.7) | 1.000 | 1.000 |
TT+CT | Yes | 312 (30.6) | 249 (24.1) | 1.367 (1.120-1.670) | 0.874 (0.686-1.112) |
CC | No | 71 (7.0) | 91 (8.8) | 0.851 (0.612-1.184) | 0.981 (0.678-1.420) |
CC | Yes | 34 (3.3) | 35 (3.4) | 1.060 (0.653-1.721) | 0.833 (0.484-1.435) |
rs6815391 × drink alcohol | ORmultiply (95% CI) | 0.983 (0.608-1.589) | 0.877 (0.515-1.496) | ||
rs6815391 with history of lung disease | |||||
TT+CT | No | 800 (78.4) | 841 (81.4) | 1.000 | 1.000 |
TT+CT | Yes | 115 (11.3) | 66 (6.4) | 1.832 (1.333-2.517) | |
CC | No | 96 (9.4) | 115 (11.1) | 0.878 (0.658-1.170) | 1.032 (0.748-1.424) |
CC | Yes | 9 (0.9) | 11 (1.1) | 0.860 (0.355-2.087) | 0.906 (0.340-2.416) |
rs6815391 × history of lung disease | ORmultiply (95% CI) | 0.827 (0.341-2.004) | 0.853 (0.320-2.277) | ||
rs6815391 with family history of cancer | |||||
TT+CT | No | 736 (72.2) | 768 (74.3) | 1.000 | 1.000 |
TT+CT | Yes | 179 (17.5) | 139 (13.5) | 1.344 (1.053-1.714) | |
CC | No | 82 (8.0) | 108 (10.5) | 0.792 (0.584-1.074) | 0.940 (0.670-1.319) |
CC | Yes | 23 (2.3) | 18 (1.7) | 1.333 (0.714-2.491) | 1.614 (0.795-3.274) |
rs6815391 × family history of cancer | ORmultiply (95% CI) | 1.301 (0.698-2.425) | 1.535 (0.758-3.106) | ||
rs3740535 | |||||
rs3740535 with pollution near the place of residence | |||||
GA+GG | No | 779 (74.3) | 934 (86.6) | 1.000 | 1.000 |
GA+GG | Yes | 196 (18.7) | 81 (7.5) | 2.901 (2.202-3.823) | |
AA | No | 61 (5.8) | 58 (5.4) | 1.261 (0.869-1.829) | 1.188 (0.784-1.800) |
AA | Yes | 12 (1.1) | 6 (0.6) | 2.398 (0.896-6.419) | 1.624 (0.537-4.911) |
rs3740535 × pollution near the place of residence | ORmultiply (95% CI) | 2.071 (0.775-5.540) | 1.419 (0.470-4.289) | ||
rs3740535 with house type | |||||
GA+GG | No | 322 (30.7) | 166 (15.4) | 1.000 | 1.000 |
GA+GG | Yes | 653 (62.3) | 849 (78.7) | 0.397 (0.320-0.491) | |
AA | No | 33 (3.1) | 12 (1.1) | 1.418 (0.713-2.817) | 1.232 (0.578-2.624) |
AA | Yes | 40 (3.8) | 52 (4.8) | 0.397 (0.252-0.624) | |
rs3740535 × house type | ORmultiply (95% CI) | 0.784 (0.514-1.194) | 0.875 (0.548-1.395) | ||
rs3740535 with ventilation situation | |||||
GA+GG | No | 37 (3.5) | 13 (1.2) | 1.000 | 1.000 |
GA+GG | Yes | 938 (89.5) | 1002 (92.9) | 0.329 (0.174-0.623) | |
AA | No | 2 (0.2) | 3 (0.3) | 0.234 (0.035-1.562) | |
AA | Yes | 71 (6.8) | 61 (5.7) | 0.409 (0.199-0.839) | |
rs3740535 × ventilation situation | ORmultiply (95% CI) | 1.213 (0.852-1.727) | 1.476 (0.475-4.529) | ||
rs3740535 with kitchen ventilator | |||||
GA+GG | No | 400 (38.2) | 305 (28.3) | 1.000 | 1.000 |
GA+GG | Yes | 575 (54.9) | 710 (65.8) | 0.618 (0.513-0.743) | 1.013 (0.804-1.275) |
AA | No | 50 (4.8) | 19 (1.8) | 2.007 (1.159-3.474) | |
AA | Yes | 23 (2.2) | 45 (4.2) | 0.390 (0.231-0.658) | 0.656 (0.366-1.178) |
rs3740535 × kitchen ventilator | ORmultiply (95% CI) | 0.516 (0.310-0.858) | 0.641 (0.365-1.123) | ||
rs3740535 with COF | |||||
GA+GG | No | 170 (16.2) | 321 (29.7) | 1.000 | 1.000 |
GA+GG | Yes | 805 (76.8) | 694 (64.3) | 2.190 (1.772-2.707) | |
AA | No | 10 (1.0) | 21 (1.9) | 0.899 (0.414-1.953) | 0.887 (0.386-2.039) |
AA | Yes | 63 (6.0) | 43 (4.0) | 2.766 (1.800-4.253) | |
rs3740535 × COF | ORmultiply (95% CI) | 1.541 (1.036-2.293) | 1.017 (0.895-1.155) | ||
rs3740535 with smoking | |||||
GA+GG | No | 376 (35.9) | 595 (55.1) | 1.000 | 1.000 |
GA+GG | Yes | 599 (57.2) | 420 (38.9) | 2.257 (1.886-2.701) | |
AA | No | 24 (2.3) | 40 (3.7) | 0.949 (0.563-1.601) | 0.903 (0.510-1.598) |
AA | Yes | 49 (4.7) | 24 (2.2) | 3.231 (1.950-5.354) | |
rs3740535 × smoking | ORmultiply (95% CI) | 2.156 (1.313-3.540) | |||
rs3740535 with passive smoking | |||||
GA+GG | No | 283 (27.0) | 557 (51.6) | 1.000 | 1.000 |
GA+GG | Yes | 692 (66.0) | 458 (42.4) | 2.974 (2.470-3.580) | |
AA | No | 27 (2.6) | 38 (3.5) | 1.398 (0.837-2.337) | 1.133 (0.641-2.005) |
AA | Yes | 46 (4.4) | 26 (2.4) | 3.48 2 (2.108-5.751) | |
rs3740535 × passive smoking | ORmultiply (95% CI) | 1.859 (1.141-3.031) | 1.560 (0.909-2.679) | ||
rs3740535 with drink alcohol | |||||
GA+GG | No | 636 (60.7) | 719 (66.6) | 1.000 | 1.000 |
GA+GG | Yes | 339 (32.3) | 296 (27.4) | 1.295 (1.072-1.564) | 0.847 (0.673-1.064) |
AA | No | 48 (4.6) | 51 (4.7) | 1.064 (0.707-1.601) | 0.906 (0.569-1.443) |
AA | Yes | 25 (2.4) | 13 (1.2) | 2.174 (1.103-4.285) | 1.566 (0.731-3.355) |
rs3740535 × drink alcohol | ORmultiply (95% CI) | 2.004 (1.020-3.938) | 1.683 (0.791-3.577) | ||
rs3740535 with history of lung disease | |||||
GA+GG | No | 859 (82.0) | 935 (86.7) | 1.000 | 1.000 |
GA+GG | Yes | 116 (11.1) | 80 (7.4) | 1.578 (1.170-2.129) | |
AA | No | 64 (6.1) | 55 (5.1) | 1.267 (0.873-1.838) | 1.199 (0.786-1.829) |
AA | Yes | 9 (0.9) | 9 (0.8) | 1.088 (0.430-2.755) | 0.920 (0.320-2.644) |
rs3740535 × history of lung disease | ORmultiply (95% CI) | 1.030 (0.407-2.605) | 0.880 (0.306-2.529) | ||
rs3740535 with family history of cancer | |||||
GA+GG | No | 783 (74.7) | 866 (80.3) | 1.000 | 1.000 |
GA+GG | Yes | 192 (18.3) | 149 (13.8) | 1.425 (1.127-1.802) | |
AA | No | 54 (5.2) | 53 (4.9) | 1.127 (0.762-1.666) | 1.209 (0.779-1.874) |
AA | Yes | 19 (1.8) | 11 (1.0) | 1.910 (0.903-4.040) | 1.189 (0.517-2.738) |
rs3740535 × family history of cancer | ORmultiply (95% CI) | 1.793 (0.849-3.786) | 1.094 (0.476-2.510) | ||
rs3130932 | |||||
rs3130932 with pollution near the place of residence | |||||
GT+TT | No | 728 (69.7) | 867 (80.1) | 1.000 | 1.000 |
GT+TT | Yes | 185 (17.7) | 80 (7.4) | 2.754 (2.081-3.645) | |
GG | No | 110 (10.5) | 129 (11.9) | 1.016 (0.773-1.334) | 1.028 (0.757-1.396) |
GG | Yes | 22 (2.1) | 6 (0.6) | 4.367 (1.761-10.827) | |
rs3130932 × pollution near the place of residence | ORmultiply (95% CI) | 3.857 (1.557-9.550) | |||
rs3130932 with house type | |||||
GT+TT | No | 302 (28.9) | 153 (14.1) | 1.000 | 1.000 |
GT+TT | Yes | 611 (58.5) | 794 (73.4) | 0.390 (0.312-0.486) | |
GG | No | 54 (5.2) | 25 (2.3) | 1.094 (0.656-1.827) | 1.433 (0.817-2.513) |
GG | Yes | 78 (7.5) | 110 (10.2) | 0.359 (0.253-0.509) | |
rs3130932 × house type | ORmultiply (95% CI) | 0.713 (0.526-0.965) | 0.832 (0.591-1.171) | ||
rs3130932 with ventilation situation | |||||
GT+TT | No | 34 (3.3) | 14 (1.3) | 1.000 | 1.000 |
GT+TT | Yes | 879 (84.1) | 933 (86.2) | 0.388 (0.207-0.728) | |
GG | No | 4 (0.4) | 1 (0.1) | 1.647 (0.169-16.070) | 2.456 (0.214-28.192) |
GG | Yes | 128 (12.2) | 134 (12.4) | 0.393 (0.202-0.767) | 0.534 (0.257-1.110) |
rs3130932 × ventilation situation | ORmultiply (95% CI) | 0.988 (0.762-1.279) | 1.063 (0.500-2.262) | ||
rs3130932 with kitchen ventilator | |||||
GT+TT | No | 396 (37.9) | 286 (26.4) | 1.000 | 1.000 |
GT+TT | Yes | 517 (49.5) | 661 (61.1) | 0.565 (0.467-0.684) | 0.926 (0.730-1.173) |
GG | No | 54 (5.2) | 40 (3.7) | 0.975 (0.630-1.508) | 1.045 (0.646-1.689) |
GG | Yes | 78 (7.5) | 95 (8.8) | 0.593 (0.424-0.830) | 1.040 (0.704-1.537) |
rs3130932 × kitchen ventilator | ORmultiply (95% CI) | 0.838 (0.613-1.145) | 1.093 (0.767-1.559) | ||
rs3130932 with COF | |||||
GT+TT | No | 162 (15.5) | 297 (27.4) | 1.000 | 1.000 |
GT+TT | Yes | 751 (71.9) | 650 (60.1) | 2.118 (1.703-2.635) | |
GG | No | 19 (1.8) | 44 (4.1) | 0.792 (0.447-1.401) | 1.017 (0.547-1.892) |
GG | Yes | 113 (10.8) | 91 (8.4) | 2.277 (1.627-3.185) | |
rs3130932 × COF | ORmultiply (95% CI) | 1.320 (0.988-1.765) | 1.013 (0.922-1.112) | ||
rs3130932 with smoking | |||||
GT+TT | No | 341 (32.6) | 557 (51.5) | 1.000 | 1.000 |
GT+TT | Yes | 572 (54.7) | 390 (36.0) | 2.396 (1.988-2.886) | |
GG | No | 52 (5.0) | 81 (7.5) | 1.049 (0.722-1.523) | 1.144 (0.759-1.724) |
GG | Yes | 80 (7.7) | 54 (5.0) | 2.420 (1.671-3.505) | |
rs3130932 × smoking | ORmultiply (95% CI) | 1.578 (1.105-2.253) | 1.414 (0.950-2.106) | ||
rs3130932 with passive smoking | |||||
GT+TT | No | 273 (26.1) | 519 (48.0) | 1.000 | 1.000 |
GT+TT | Yes | 640 (61.2) | 428 (39.6) | 2.843 (2.349-3.441) | |
GG | No | 38 (3.6) | 81 (7.5) | 0.892 (0.591-1.347) | 0.934 (0.597-1.460) |
GG | Yes | 94 (9.0) | 54 (5.0) | ||
rs3130932 × passive smoking | ORmultiply (95% CI) | 1.882 (1.331-2.660) | 1.778 (1.214-2.604) | ||
rs3130932 with drink alcohol | |||||
GT+TT | No | 592 (56.7) | 678 (62.7) | 1.000 | 1.000 |
GT+TT | Yes | 321 (30.7) | 269 (24.9) | 1.367 (1.123-1.663) | 0.882 (0.696-1.119) |
GG | No | 89 (8.5) | 96 (8.9) | 1.062 (0.780-1.446) | 1.111 (0.785-1.573) |
GG | Yes | 43 (4.1) | 39 (3.6) | 1.263 (0.807-1.975) | 0.934 (0.560-1.557) |
rs3130932 × drink alcohol | ORmultiply (95% CI) | 1.148 (0.738-1.786) | 0.968 (0.586-1.598) | ||
rs3130932 with history of lung disease | |||||
GT+TT | No | 805 (77.0) | 872 (80.6) | 1.000 | 1.000 |
GT+TT | Yes | 108 (10.3) | 75 (6.9) | 1.560 (1.144-2.126) | |
GG | No | 117 (11.2) | 120 (11.1) | 1.056 (0.805-1.386) | 1.165 (0.857-1.583) |
GG | Yes | 15 (1.4) | 15 (1.4) | 1.083 (0.526-2.230) | 0.962 (0.421-2.196) |
rs3130932 × history of lung disease | ORmultiply (95% CI) | 1.036 (0.504-2.130) | 0.914 (0.401-2.085) | ||
rs3130932 with family history of cancer | |||||
GT+TT | No | 731 (70.0) | 809 (74.8) | 1.000 | 1.000 |
GT+TT | Yes | 182 (17.4) | 138 (12.8) | 1.460 (1.145-1.861) | |
GG | No | 105 (10.0) | 112 (10.3) | 1.038 (0.781-1.379) | 1.093 (0.793-1.507) |
GG | Yes | 27 (2.6) | 23 (2.1) | 1.299 (0.738-2.286) | 1.632 (0.862-3.092) |
rs3130932 × family history of cancer | ORmultiply (95% CI) | 1.221 (0.696-2.144) | 1.520 (0.805-2.873) |
#By the degree of education, marital status, BMI, pollution near the place of residence, house type, ventilation situation, COF, kitchen ventilator, smoking, passive smoking, drink alcohol, history of lung disease, and family history of cancer adjusted. OR and its interval shown in italic font to represent the
The interaction analysis for both the dominant or recessive models showed that there was no additive interaction between the
Smoking interaction with four gene loci.
rs13409 dominant genetic model | Smoking | 0.047 | 0.010 | 1.013 |
(-1.232-1.325) | (-0.264-0.284) | (0.712-1.441) | ||
rs13409 recessive genetic model | Smoking | -0.638 | -0.160 | 0.824 |
(-2.689-1.412) | (-0.658-0.338) | (0.478-1.422) | ||
rs3130932 dominant genetic model | Smoking | 0.303 | 0.074 | 1.108 |
(-0.805-1.411) | (-0.186-0.333) | (0.761-1.611) | ||
rs3130932 recessive genetic model | Smoking | -0.107 | -0.031 | 0.958 |
(-1.673-1.459) | (-0.488-0.425) | (0.516-1.776) | ||
rs3740535 dominant genetic model | Smoking | -0.460 | -0.116 | 0.866 |
(--1.662-0.742) | (-0.428-0.195) | (0.601-1.247) | ||
rs3740535 recessive genetic model | Smoking | -1.240 | -0.306 | 0.711 |
(-4.376-1.896) | (-1.036-0.423) | (0.359-1.409) | ||
rs6815391 dominant genetic model | Smoking | -1.007 | -0.247 | 0.754 |
(-2.298-0.284) | (-0.584-0.090) | (0.532-1.067) | ||
rs6815391 recessive genetic model | Smoking | -0.657 | -0.154 | 0.833 |
(-2.855-1.541) | (-656-0.349) | (0.483-1.437) |
As can be observed in Tables
Multivariate analysis.
Variable | OR (OR 95% CI) | ||
---|---|---|---|
Junior and senior high school | 0.125 | 0.442 | 1.133 (0.824-1.556) |
College degree or above | -0.329 | 0.036 | |
Others (marital status) | 1.889 | 0.006 | |
Single (marital status) | 1.813 | 0.012 | |
1.300 | <0.001 | ||
0.512 | <0.001 | ||
Building (with cottage ratio) | 0.409 | 0.436 | 1.505 (0.538-4.209) |
Ventilation general | -0.805 | 0.014 | |
Ventilation worse | -0.103 | 0.767 | 0.902 (0.455-1.787) |
Not pollution near the place of residence | -0.843 | <0.001 | |
Kitchen ventilator | -0.051 | 0.648 | 0.950 (0.764-1.182) |
Much fumes | 1.115 | <0.001 | |
Some fumes | 0.535 | <0.001 | |
Little fumes | 0.630 | <0.001 | |
Smoking | 0.653 | <0.001 | |
Passive smoking | 0.865 | <0.001 | |
History of lung disease | 0.333 | 0.037 | |
Family history of cancer | 0.348 | 0.006 | |
Drink alcohol | -0.104 | 0.349 | 0.901 (0.725-1.120) |
1 protected genotypes | -0.486 | 0.006 | |
2 protected genotypes | -0.291 | 0.030 | |
3 protected genotypes | -0.154 | 0.199 | 0.857 (0.677-1.085) |
#OR and its interval shown in italic font to represent the
In our current study, the relationship between each of the four SNPs and the risk of lung cancer among 1121 patients and 1121 controls were estimated. The unconditional logistic regression analysis results showed no association between
The expression of
Studies on the association between the
After analyzing the interaction between the two genotypes of
Vertebrates contain two different
This study found that the genotype frequency distribution of
Our results showed the combined effect of the four genotypes with the environmental factors of pollution near the place of residence, worse ventilation situation, smoking, passive smoking, COF, and family history of cancer. These factors together increase the risk of lung cancer in the population. We did not see an additive interaction between the four locus polymorphisms and smoking. The genotypes were related to the survival outcome of lung cancer patients. The number of protective genotypes of the four loci divided into different groups to evaluate its combined effect with the factors influencing lung cancer in the univariate analysis was also included in the logistic multivariate analysis. Our results showed that unmarried status, BMI, COF, smoking, passive smoking, family history of cancer, and history of lung disease were independent risk factors of lung cancer; college degree or above, no pollution near the place of residence, 1 or 2 protective genotypes, and well ventilation can reduce the occurrence of lung cancer.
The sample size was large, and the power of the results was high in the current study. However, our study had limitations. First, we could not completely rule out selection bias, although this was one of the objectives of using three of the largest flow hospitals. Second, the functional studies should be confirmed. Third, environmental factors were significantly different between the two groups, so the relationship between lung cancer and SNPs could not be directly determined. Therefore, the multivariate regression analysis was used for removing the influence of confounders and to explore the relationship between SNPs and lung cancer.
In conclusion, our study indicated that the
The datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request.
This study was approved by the Institutional Review Board of Fujian Medical University (Fuzhou, China), and all participants signed informed consent forms.
The authors declare that they have no conflicts of interest.
SQ carried out the experiments and helped draft the manuscript. LZQ, XQP, and QML carried out the experiments and collected the samples. HZJ and WWX participated in the design of the study and performed the statistical analysis. HF and LC conceived of the study and participated in its design and coordination and helped draft the manuscript. All authors read and approved the final manuscript.
This study was supported by grants from the National Natural Science Foundation of China (No. 81402738), Fujian Provincial Natural Science Foundation Project (No. 2016J01355), Fujian Program for Outstanding Young Researchers in University awarded by the Education Department of Fujian (No. 2017B019), and the National Key Research and Development Program of China (No. 2017YFC0907100). We thank all the staffs from the Department of Thoracic Surgery, The First Affiliated Hospital of Fujian Medical University. We would also like to express our appreciation to the patients who participated in our study.
Supplementary Table 1: The genomic location of the four SNPs.