Supplement Table 1. Primer sequences for FHIT sequence variants screening

Gene Name / Forward Primer / Sequence / Reverse Primer / Sequence
FHIT / 2272_FHIT_1F / CCAGCAGTCAGCATTATCCA / 2272_FHIT_1R / TCGGGAAAAACAAAGAGCAG
2272_FHIT_2F / GCCATGGTGTCTGTGTGATG / 2272_FHIT_2R / GCATTTGTCGTTACGAAGCA
2272_FHIT_3F / TGCTGGGCACTTTTCTAGGTG / 2272_FHIT_3R / ACTGCAATTCCCAGAAGACCC
2272_FHIT_4F / TTCTGTGGTCAGTGTTTCCCG / 2272_FHIT_4R / ACAGACCTGTTGGGACGGATT
2272_FHIT_5F / AGATTTGGCCAAGGTTTGTG / 2272_FHIT_5R / CCCAATTGAAATGCCACTCT
2272_FHIT_6F / ACTGCCCTACAAGATGTCCC / 2272_FHIT_6R / CCCTTTCCTCCTTACGAAGAT
2272_FHIT_7F / GATGTGGCTGAAACAACCCT / 2272_FHIT_7R / ATGGAAAAGAAGGGGAATGC
2272_FHIT_8F / CGAATGTCCCTTTCTTTTGC / 2272_FHIT_8R / CCACCCTGGAATTAGAGCAG
2272_FHIT_9F / CCCAAACATTTTCAGCCTTCC / 2272_FHIT_9R / TTAACATGGGGCTGCACAAAC
2272_FHIT_10F / GCACTCTCTTCTCGGCAGAT / 2272_FHIT_10R / TGCTGTTGGGAAAGACAAGC
2272_FHIT_11F / CCCCCTCAGCCTCAGTAGATG / 2272_FHIT_11R / AGCTGGTTTACAGGGCTTTGC

Supplement Table 2. Sequences of amplifying, Taqman probe for FHIT polymorphisms genotyping

Gene / Loci
FHIT / -715859A>T / Forward / CAGTCTGTACATATATTGCTCACATTCCT
Reverse / ACCATGGCCACATAAAATATTATCAAATTGTG
VIC / CTGTTTTAACTATATATTTTTTT
FAM / CTGTTTTAACTATATTTTTTTTT
-715821A>G / Forward / TGCTCACATTCCTGCTGTTTTAACT
Reverse / ACAGACACCATGGCCACAT
VIC / TTCACAATTTGATAATATTTT
FAM / ACAATTTGATGATATTTT
-715523T>C / Forward / GGGACCTATCTTAGTGTTTGTCTGAGA
Reverse / TTCCTGGCTGCAGACTCTTG
VIC / CCATTACATCAGGAAAA
FAM / CCATTACATCGGGAAAA
-714528G>C / Forward / GGGTTACTGTCACTATGGCTTTCAA
Reverse / GGAGCGGAGGCCAATACG
VIC / CCTACGCCGGGCCA
FAM / CCTAGGCCGGGCCA
-663785C>T / Forward / CACCATTTTCAGTTTCTGACTGTCTTT
Reverse / TGGTGCTAGCCAAATAAACCATTGA
VIC / AACTTGTGCCTCGTACCT
FAM / CTTGTGCCTCATACCT
-285126G>A / Forward / ATGACAATGCCTGCAAAAATCACAT
Reverse / GTTCACCATGAATACTGAGCATTGC
VIC / CGCTTTTAACAGTACCTGT
FAM / CGCTTTTAACAATACCTGT
+523001A>G / Forward / ATGCAGGTGAGTGTACAGATTTCTC
Reverse / GAGGAGCAAGCCCAATGC
VIC / TCCCTTTCATATCCC
FAM / CCCTTTCGTATCCC
+525722G>A / Forward / CTGTTTCATTATGTTATCTTCGAGGTCAGA
Reverse / TGTTTGGCAGAGTTTATAATGTCAGGAT
VIC / ACCCTCAGTGTTAGAGC
FAM / ACCCTCAATGTTAGAGC
+614565T>C / Forward / AGAGCATCACTGTCAAGTCTAAAAATACA
Reverse / GTGAAAGTCTCCAGCCTTCCT
VIC / TCACGTCCATGTTCTT
FAM / ACGTCCACGTTCTT
+784627T>A / Forward / TCCCAAGGGCCCATGAAAG
Reverse / TGTCATGTTTCTGGAGCTTTGGA
VIC / AGCCTCTTCCTTTTTT
FAM / CCTCTTCCATTTTT
+784722C>T / Forward / AGGAGGAAATGGCAGCAGAAG
Reverse / AAATGCAGTCTTTACCTGTGTCACT
VIC / AAAGTAGACCCGCAGAGC
FAM / AAGTAGACCCACAGAGC

Supplement Table 3.Logistic analysis of FHIT polymorphisms with the risk of lung cancer whilst controlling for age,sex, smoking status as covariates in dominant and recessive models among lung cancer and normal subjects.

Loci / Genotype / Case / Control / Dominant / Recessive
OR (95% CI) / Adjusted OR (95% CI) / P / Pcorr / OR (95% CI) / Adjusted OR (95% CI) / P / Pcorr
-715859A>T / AA / 189 (68.2 %) / 203 (69.3 %)
AT / 79 (28.5 %) / 83 (28.3 %) / 1.05
(0.74 -1.50 ) / 0.94
(0.61-1.44) / 0.78 / NS / 1.37 (0.50 -3.74 ) / 1.34(0.35-5.12) / 0.67 / NS
TT / 9 (3.3 %) / 7 (2.4 %)
-715821A>G / AA / 151 (54.1 %) / 154 (52.9 %)
AG / 108 (38.7 %) / 104 (35.7 %) / 0.95
(0.69 -1.32 ) / 0.92
(0.62-1.37) / 0.69 / NS / 0.60 (0.34 -1.08 ) / 0.64(0.32-1.27) / 0.20 / NS
GG / 20 (7.2 %) / 33 (11.3 %)
-715523T>C / TT / 190 (68.4 %) / 201 (68.8 %)
CT / 80 (28.8 %) / 82 (28.1 %) / 1.02
(0.72 -1.46 ) / 0.91
(0.59-1.40) / 0.66 / NS / 0.93 (0.35 -2.45 ) / 0.81(0.23-2.83) / 0.74 / NS
CC / 8 (2.9 %) / 9 (3.1 %)
-714528G>C / GG / 96 (34.4 %) / 102 (34.8 %)
CG / 121 (43.4 %) / 127 (43.3 %) / 1.02
(0.72 -1.44 ) / 1.15
(0.76-1.74) / 0.51 / NS / 1.02 (0.69 -1.52 ) / 1.00(0.63-1.59) / 0.99 / NS
CC / 62 (22.2 %) / 64 (21.8 %)
-663785C>T / CC / 109 (39.5 %) / 113 (38.7 %)
CT / 128 (46.4 %) / 130 (44.5 %) / 0.97
(0.69 -1.36 ) / 0.89
(0.60-1.34) / 0.58 / NS / 0.82 (0.52 -1.29 ) / 0.83(0.48-1.44) / 0.51 / NS
TT / 39 (14.1 %) / 49 (16.8 %)
-285126G>A / GG / 141 (51.5 %) / 169 (58.1 %)
AG / 109 (39.8 %) / 108 (37.1 %) / 1.31
(0.94 -1.82 ) / 1.07
(0.72-1.60) / 0.73 / NS / 1.90 (0.96 -3.75 ) / 1.55(0.65-3.70) / 0.32 / NS
AA / 24 (8.8 %) / 14 (4.8 %)
ht1 / -/- / 147 (53.1 %) / 144 (49.3 %)
-/ht1 / 107 (38.6 %) / 129 (44.2 %) / 0.86
(0.62 -1.20 ) / 0.90
(0.60-1.33) / 0.59 / NS / 1.30 (0.69 -2.45 ) / 1.50(0.70-3.21) / 0.30 / NS
ht1/ht1 / 23 (8.3 %) / 19 (6.5 %)
ht2 / -/- / 179 (64.6 %) / 171 (58.6 %)
-/ht2 / 86 (31.1 %) / 99 (33.9 %) / 0.77
(0.55 -1.09 ) / 0.78
(0.52-1.17) / 0.23 / NS / 0.56 (0.27 -1.15 ) / 0.82(0.35-1.95) / 0.66 / NS
ht2/ht2 / 12 (4.3 %) / 22 (7.5 %)
ht3 / -/- / 206 (74.4 %) / 231 (79.1 %)
-/ht3 / 69 (24.9 %) / 57 (19.5 %) / 1.31
(0.88 -1.93 ) / 1.18
(0.75-1.88) / 0.47 / NS / 0.52 (0.10 -2.88 ) / 0.92(0.13-6.49) / 0.93 / NS
ht3/ht3 / 2 (0.7 %) / 4 (1.4 %)
ht4 / -/- / 218 (78.7 %) / 239 (81.9 %)
-/ht4 / 52 (18.8 %) / 49 (16.8 %) / 1.22
(0.81 -1.85 ) / 1.25
(0.76-2.04) / 0.38 / NS / 1.87 (0.54 -6.45 ) / 2.98(0.76-11.74) / 0.12 / NS
ht4/ht4 / 7 (2.5 %) / 4 (1.4 %)
ht5 / -/- / 239 (86.3 %) / 253 (86.6 %)
-/ht5 / 36 (13.0 %) / 38 (13.0 %) / 1.03
(0.64 -1.67 ) / 0.97
(0.54-1.73) / 0.91 / NS / 2.12 (0.19-23.47 ) / 1.21(0.05-30.37) / 0.91 / NS
ht5/ht5 / 2 (0.7 %) / 1 (0.3 %)
+523001A>G / AA / 150 (53.8 %) / 179 (61.3 %)
AG / 114 (40.9 %) / 102 (34.9 %) / 1.36
(0.98 -1.90 ) / 1.31
(0.88-1.96) / 0.18 / NS / 1.45 (0.66 -3.22 ) / 2.53(0.85-7.50) / 0.10 / NS
GG / 15 (5.4 %) / 11 (3.8 %)
+525722G>A / GG / 106 (38.3 %) / 135 (46.2 %)
AG / 134 (48.4 %) / 133 (45.6 %) / 1.39
(0.99 -1.94 ) / 1.47
(0.99-2.20) / 0.06 / NS / 1.72 (1.00 -2.96 ) / 1.86(0.96-3.63) / 0.07 / NS
AA / 37 (13.4 %) / 24 (8.2 %)
+614565T>C / TT / 107 (38.6 %) / 113 (38.8 %)
CT / 123 (44.4 %) / 127 (43.6 %) / 1.01
(0.72 -1.41 ) / 0.84
(0.56-1.26) / 0.40 / NS / 0.96 (0.62 -1.49 ) / 0.60(0.35-1.02) / 0.06 / NS
CC / 47 (17.0 %) / 51 (17.5 %)
+784627T>A / TT / 165 (67.4 %) / 168 (59.2 %)
AT / 68 (27.8 %) / 108 (38.0 %) / 0.70
0.49 -1.00 ) / 0.75
(0.49-1.15) / 0.19 / NS / 1.78 (0.71 -4.42 ) / 3.24(1.05-9.95) / 0.04 / NS
AA / 12 (4.9 %) / 8 (2.8 %)

Logistic regression models were used for calculating crude and adjusted odds ratios (95% confidential interval) and corresponding P-values of codominant model for each SNP site and haplotype.

Supplement Table 4. Logistic regression analysis of FHIT polymorphisms with historical type of lung cancer controlling age, sex and smoking status

Historical type of lung cancer / Loci / Case (n=117) / Control (n=293) / OR (95% CI) / P / Pcorr*
Adeno-carcinoma / -715859A>T / 0.187 / 0.166 / 1.24 (0.73 -2.12 ) / 0.42 / NS
-715821A>G / 0.276 / 0.292 / 0.96 (0.63 -1.45 ) / 0.83 / NS
-715523T>C / 0.185 / 0.171 / 1.12 (0.67 -1.88 ) / 0.67 / NS
-714528G>C / 0.435 / 0.435 / 1.01 (0.71 -1.45 ) / 0.95 / NS
-663785C>T / 0.391 / 0.390 / 1.09 (0.74 -1.59 ) / 0.68 / NS
-285126G>A / 0.323 / 0.234 / 1.28 (0.80 -2.05 ) / 0.30 / NS
ht1 / 0.257 / 0.286 / 0.86 (0.54 -1.36 ) / 0.51 / NS
ht2 / 0.178 / 0.245 / 0.78 (0.48 -1.28 ) / 0.33 / NS
ht3 / 0.148 / 0.111 / 1.42 (0.79 -2.55 ) / 0.24 / NS
ht4 / 0.113 / 0.098 / 1.10 (0.59 -2.02 ) / 0.77 / NS
ht5 / 0.078 / 0.068 / 1.47 (0.71 -3.06 ) / 0.30 / NS
+523001A>G / 0.241 / 0.212 / 1.11 (0.66 -1.87 ) / 0.68 / NS
+525722G>A / 0.388 / 0.310 / 1.43 (0.93 -2.21 ) / 0.10 / NS
+614565T>C / 0.372 / 0.393 / 0.71 (0.48 -1.05 ) / 0.08 / NS
+784627T>A / 0.186 / 0.218 / 1.04 (0.61 -1.76 ) / 0.90 / NS
+784722C>T / 0.009 / 0.000 / . / . / .
Case (n=81) / Control (n=293)
Squamous-carcinoma / -715859A>T / 0.156 / 0.166 / 1.09 (0.60 -1.96 ) / 0.78 / NS
-715821A>G / 0.278 / 0.292 / 0.90 (0.58 -1.40 ) / 0.64 / NS
-715523T>C / 0.160 / 0.171 / 1.02 (0.58 -1.80 ) / 0.94 / NS
-714528G>C / 0.432 / 0.435 / 1.00 (0.68 -1.46 ) / 0.98 / NS
-663785C>T / 0.373 / 0.390 / 0.94 (0.62 -1.43 ) / 0.76 / NS
-285126G>A / 0.234 / 0.234 / 0.93 (0.57 -1.52 ) / 0.77 / NS
ht1 / 0.288 / 0.286 / 1.09 (0.68 -1.75 ) / 0.72 / NS
ht2 / 0.225 / 0.245 / 0.86 (0.53 -1.39 ) / 0.53 / NS
ht3 / 0.113 / 0.111 / 0.83 (0.44 -1.57 ) / 0.57 / NS
ht4 / 0.138 / 0.098 / 1.38 (0.76 -2.49 ) / 0.29 / NS
ht5 / 0.063 / 0.068 / 0.87 (0.37 -2.03 ) / 0.75 / NS
+523001A>G / 0.253 / 0.212 / 1.32 (0.80 -2.20 ) / 0.28 / NS
+525722G>A / 0.399 / 0.310 / 1.70 (1.10 -2.65 ) / 0.02 / NS
+614565T>C / 0.388 / 0.393 / 0.69 (0.46 -1.02 ) / 0.06 / NS
+784627T>A / 0.182 / 0.218 / 0.85 (0.49 -1.49 ) / 0.57 / NS
+784722C>T / 0.000 / 0.000 / . / . / .
Case (n=43) / Control (n=293)
Small Cell Lung Cancer / -715859A>T / 0.186 / 0.166 / 0.86 (0.41 -1.79 ) / 0.68 / NS
-715821A>G / 0.186 / 0.292 / 0.56 (0.30 -1.04 ) / 0.07 / NS
-715523T>C / 0.167 / 0.171 / 0.76 (0.37 -1.60 ) / 0.47 / NS
-714528G>C / 0.500 / 0.435 / 1.33 (0.83 -2.11 ) / 0.24 / NS
-663785C>T / 0.302 / 0.390 / 0.65 (0.38 -1.12 ) / 0.12 / NS
-285126G>A / 0.305 / 0.234 / 1.38 (0.76 -2.49 ) / 0.29 / NS
ht1 / 0.326 / 0.286 / 1.48 (0.84 -2.61 ) / 0.17 / NS
ht2 / 0.163 / 0.245 / 0.57 (0.29 -1.12 ) / 0.10 / NS
ht3 / 0.140 / 0.111 / 1.24 (0.58 -2.66 ) / 0.58 / NS
ht4 / 0.093 / 0.098 / 0.93 (0.41 -2.14 ) / 0.87 / NS
ht5 / 0.070 / 0.068 / 1.08 (0.38 -3.02 ) / 0.89 / NS
+523001A>G / 0.302 / 0.212 / 1.76 (0.97 -3.20 ) / 0.06 / NS
+525722G>A / 0.360 / 0.310 / 1.65 (0.93 -2.91 ) / 0.09 / NS
+614565T>C / 0.402 / 0.393 / 0.78 (0.47 -1.29 ) / 0.33 / NS
+784627T>A / 0.243 / 0.218 / 1.07 (0.55 -2.09 ) / 0.85 / NS
+784722C>T / 0.000 / 0.000 / . / .
Case (n=16) / Control (n=293)
Other types of lung cancer / -715859A>T / 0.094 / 0.166 / 0.56 (0.15 -2.04 ) / 0.38 / NS
-715821A>G / 0.406 / 0.292 / 1.56 (0.73 -3.33 ) / 0.25 / NS
-715523T>C / 0.094 / 0.171 / 0.53 (0.15 -1.90 ) / 0.33 / NS
-714528G>C / 0.438 / 0.435 / 1.03 (0.50 -2.12 ) / 0.94 / NS
-663785C>T / 0.469 / 0.390 / 1.36 (0.65 -2.85 ) / 0.42 / NS
-285126G>A / 0.188 / 0.234 / 0.86 (0.33 -2.24 ) / 0.76 / NS
ht1 / 0.281 / 0.286 / 0.91 (0.36 -2.32 ) / 0.85 / NS
ht2 / 0.344 / 0.245 / 1.56 (0.69 -3.54 ) / 0.29 / NS
ht3 / 0.125 / 0.111 / 1.28 (0.41 -4.03 ) / 0.67 / NS
ht4 / 0.094 / 0.098 / 0.85 (0.23 -3.12 ) / 0.81 / NS
ht5 / 0.063 / 0.068 / 0.94 (0.19 -4.70 ) / 0.94 / NS
+523001A>G / 0.219 / 0.212 / 1.03 (0.37 -2.81 ) / 0.96 / NS
+525722G>A / 0.250 / 0.310 / 1.03 (0.42 -2.51 ) / 0.95 / NS
+614565T>C / 0.500 / 0.393 / 1.07 (0.51 -2.25 ) / 0.86 / NS
+784627T>A / 0.179 / 0.218 / 0.63 (0.19 -2.08 ) / 0.45 / NS
+784722C>T / 0.000 / 0.000 / . / . / .

Logistic regression models were used for calculating crude and adjusted odds ratios (95% confidential interval) and corresponding P-values of codominant model for each SNP site and haplotype. * See table legend of Table 3.

Supplement Table 5. Logistic regression analysis of FHIT polymorphisms with lung cancer stratified by smoking

Loci / Smokers / Non-smokers
Lung cancer / NC / OR (95% CI) / P / Pcorr / Lung cancer / NC / OR (95% CI) / P / Pcorr
-715859A>T / 0.172 / 0.163 / 0.95(0.63-1.44) / 0.81 / NS / 0.184 / 0.172 / 1.10(0.41-2.97) / 0.85 / NS
-715821A>G / 0.266 / 0.304 / 0.85(0.61-1.17) / 0.31 / NS / 0.263 / 0.264 / 1.14(0.49-2.65) / 0.77 / NS
-715523T>C / 0.172 / 0.171 / 0.89(0.59-1.33) / 0.56 / NS / 0.173 / 0.172 / 1.10(0.41-2.96) / 0.86 / NS
-714809A>T / 0.000 / 0.000 / . / . / . / 0.000 / 0.000 / . / . / .
-714528G>C / 0.441 / 0.431 / 1.07(0.81-1.41) / 0.64 / NS / 0.434 / 0.444 / 1.09(0.51-2.34) / 0.83 / NS
-663785C>T / 0.371 / 0.394 / 0.87(0.65-1.18) / 0.37 / NS / 0.380 / 0.382 / 1.20(0.52-2.78) / 0.66 / NS
-285126G>A / 0.281 / 0.239 / 1.15(0.81-1.63) / 0.45 / NS / 0.300 / 0.222 / 0.99(0.38-2.55) / 0.98 / NS
ht1 / 0.271 / 0.271 / 1.04(0.74-1.45) / 0.84 / NS / 0.289 / 0.320 / 0.88(0.37-2.12) / 0.78 / NS
ht2 / 0.209 / 0.246 / 0.83(0.58-1.18) / 0.30 / NS / 0.171 / 0.242 / 0.90(0.34-2.43) / 0.84 / NS
ht3 / 0.137 / 0.123 / 1.15(0.73-1.80) / 0.56 / NS / 0.118 / 0.084 / 1.25(0.35-4.55) / 0.73 / NS
ht4 / 0.117 / 0.101 / 1.29(0.82-2.03) / 0.26 / NS / 0.125 / 0.090 / 0.89(0.24-3.27) / 0.86 / NS
ht5 / 0.072 / 0.069 / 0.92(0.51-1.64) / 0.77 / NS / 0.072 / 0.067 / 1.75(0.35-8.79) / 0.50 / NS
+523001A>G / 0.256 / 0.204 / 1.37(0.95-1.98) / 0.09 / NS / 0.263 / 0.230 / 1.21(0.42-3.46) / 0.73 / NS
+525722G>A / 0.356 / 0.318 / 1.30(0.93-1.81) / 0.12 / NS / 0.428 / 0.292 / 2.25(1.01-5.03) / 0.05 / NS
+614565T>C / 0.376 / 0.416 / 0.79(0.59-1.06) / 0.12 / NS / 0.433 / 0.343 / 0.95(0.42-2.16) / 0.91 / NS
+784627T>A / 0.186 / 0.213 / 0.83(0.57-1.22) / 0.35 / NS / 0.192 / 0.232 / 4.28(1.05-17.46) / 0.04 / NS
+784722C>T / 0.007 / 0.000 / . / . / . / 0.000 / 0.000 / . / . / .