Pharmacogenetic and Germline Prognostic Markers of Lung Cancer
Anne M. Horgan, MB BCh, MRCPI; Boming Yang; Abul Kalam Azad, MBBS, MSc, PhD;
Eitan Amir, MB ChB; Thomas John, MBBS, PhD, FRACP; David W. Cescon, MD; Paul
Wheatley-Price, MB BCh; Rayjean J. Hung, PhD, MSc; Frances A. Shepherd, MD,
FRCP(C); Geoffrey Liu, MD, MSc, FRCPC
Princess Margaret Hospital, 610 University Avenue, Toronto, Ontario, Canada, M5G 2M9
1
Supplementary Table 1A. Pathways/Polymorphisms most frequently studied
Genetic
Polymorphism
XRCC1 4-13
XRCC1 Arg399Gln
Studies
Comment: Positive Findings
10 studies
4 Asian; 6 Caucasian
n= 38-229
XRCC1 Arg194Trp
4 studies
3 Asian; 1 Caucasian
n=36-229
XRCC1 Arg280His
1 study
Asian; n=229
TREATMENT WITH PLATINUM
Gln allele → better OS in three Caucasian studies 4-6
Gln/Gln → worse OS in one US study 9
Gln/- → worse grade 3 or 4 toxicity in a single Asian study
[AOR 2.05 (p=0.04)] 13.
Arg/Trp → better RR to platinum in single study (p=0.04) 7.
Trp/- → worse toxicity with gemcitabine/docetaxel (p=0.03) 10
Arg/Arg → better PFS (radiation alone) (p=0.03) 11
Arg/Arg → no association with cisplatin in single study 13.
No significant associations 11
ERCC15,6,20-26,75,82
ERCC1 C118T
DNA REPAIR
ERCC1 C8092A
ERCC1(G262T;T433C;
C4855T)
XPD 4,5,8-10,21,25,83,84
XPD Asp312Asn
9 studies
4 Asian; 5 Caucasian
n=65-245
6 studies
2 Asian; 4 Caucasian
n= 119-423
1 study
Asian; n=162
TREATMENT WITH PLATINUM
C/C → better OS/RR in three Asian studies20-22
C/C → No associations in 4 Caucasian studies6,24-26
C/- → independently associated with better response in a single
European study compared to T/T [OR 0.10; p=0.03] 5
C/C → better OS in 2 studies 23,26.
C/C → poorer OS in 2 studies 5,75.
C/C → less toxicity in a single study 24.
262T/T → worse OS [AHR 1.98; p=0.02] :SCLC only, treated
with carboplatin/VP16 82
6 studies
2 Asian; 4 Caucasian
n=39-209
7 studies
2 Asian; 5 Caucasian
n=39-248
1 Study
Asian; n=209
TREATMENT WITH PLATINUM
312Asn/Asn →worse OS in a single study (p=0.003) 9.
No significant associations in remaining studies 5,21,25,83,84
751Lys/Lys → higher incidence Gr 4 neutropenia (p=0.02) 10.
No significant associations in remaining studies 4,5,8,21,25,83
6 studies
1 Mixed; 2 Caucasian
3 Asian
n=53-214
NO GEMCITABINE
37C/C - 524T/T haplotype → better DFS compared to 37A/C524C/T [AHR 0.59; p= 0.05] 85
524C/T → better RR than 524C/C or T/T with platinum therapy
(p=0.05) 86
TREATMENT WITH GEMCITABINE
37A/C-524C/T haplotype → better RR compared to other
allelotypes (p=0.04) 88
No association in the overall population in a second study 6
Pathway analyses 75,76
25 SNPs in 16 genes in
DNA repair pathways
1 Study
Caucasian; n=229
6 polymorphisms in nucleotide excision gene associated with
OS, though not significant 75
109 SNPs in 50 DNA
repair genes
1 Study
Caucasian; n=700
15 polymorphisms associated with OS mostly in nucleotide
excision and base excision repair pathways; interactions with
platinum76
XPD Lys751Gln
XPD C156A
XPD Asp711Asp
RRM1 6,85-89
RRM1 -A37C
RRM1-C524T
RRM1 T756C
RRM1 C269A
156A/A → higher incidence of grade 3/4 haematological
toxicity in platinum-treated patients than C/C or C/A (p=0.01)84
2
DNA REPAIR
Supplementary Table 1A cont’d. Pathways/Polymorphisms most frequently studied
Genetic
Polymorphism
Others 7,22,25,73,87,89-92
iASPP A67T
ATM A60G
APE1 Asn148Glu
MDR1 (C3435T;
2677GT/3435CT*)
CDA Lys27Gln
CDA C435T
hMSH2 gIVS12-6T/C
EGFR TKI
XPG (His46His;
His1104Asp; XPA
A23G
BRCA1 Tagging
polymorphisms
EGFR 32-39,93-95
EGFR intron 1
(CA)nS/L
(S=short ; L=long)
Comment: Positive Findings
1 Study
Asian; n=230
iASPP 67A/- → better RR (p=0.01) only in a
cisplatin/radiation subgroup 22
2 Studies
1 Asian; 1 Caucas
n=54-62
2 Studies
1 Asian, 1 Caucas
n=53, 65
1 Study
Asian; n=156
2 Studies
Asian; n=82-115
3435C/C → better RR in Asian study compared to T/(p=0.03) 92. No association in Caucasian study 87
1 Study
Asian; n=300
7 studies
4 Asian; 3 Caucasian
n = 70-170
EGFR -G216T
EGFR -216G/-191C*
3 studies
3 Caucasian
n= 92-173
EGFR G2607A
EGFR C2982T
3 Studies
Asian n=46 - 84
ABCG2 C421A
ABCG2 G34A;
ABCC3 C211T;
ABCC3 G3890A;
ABCC3 C3942T;
2 studies
Caucasian; n=173,349
p53 / MDM2 43-50
p53 Arg72Pro
p53 Intron 3 (single
study)
MDM2 T309G
OTHER
Studies
GST 5,52,53,63,65,66,96-99
GSTM1-null/present
GSTT1-null/present
GSTP1 Ile105Val
GSTP1 A/G
GSTP1Ala114Val
γ-GCS-7/8
CDA Lys/Lys → better OS in a single study (p=0.002)
compared to Lys/Gln or Gln/Gln 25
hMSH2 T/T →worse OS (p=0.003) in a single study compared
to C/C or T/C 91.
XPA G/- → better response than AA to platinum-based therapy
[OR 0.2; p=0.004] 90
No association in second study 7
AACC wild type haplotype → shorter survival [AHR 2.10;
p=0.001] 73
TREATMENT WITH GEFITINIB
LL → worse OS in a single Asian study (p=0.04) 32
L/- → worse PFS in a Caucasian study [AHR 1.9; p=0.03] 35
LL → worse RR in an Asian study alone or with a D994D
polymorphism (p<0.001) 37
L → worse RR (p=0.03) and TTP (p=0.01) in Asian study 36
NO GEFITINIB
L → better OS in a single US study [HR 0.66; p=0.03] 38
TREATMENT WITH GEFITINIB
216G/G → worse PFS, alone or in combination with Intron 1
L allele in one study 35
EGFR*1(-216G/-191C) haplotype → worse OS (p=0.02),
only in ECOG PS 0 /1 patients, in 2nd study 33
TREATMENT WITH GEFITINIB
2607G/G → better OS than A/- (p=0.07)94
2982 C/C → longer PFS compared to T/- (p=0.002)37
TREATMENT WITH GEFITINIB
ABCG2 421A/- →.higher incidence of diarrhea (p=0.005) 39
NO GEFITINIB
ABCG2 421A/- → worse OS than C/C [HR 1.6 (1.04-2.47)]
(with platinum) 93
ABCC3 211T/- variants → poorer PFS [HR 1.8 (1.13-2.82)] in
a small cell subgroup 93
7 studies
3 Asian; 4 Caucasian
n=101-619
2 studies
1 Asian; 1 Caucasian
n=148, 383
Arg/Pro → worse OS in 1 study [AHR 2.3; p=0.02] 43
Pro/Pro → worse OS in 1study 44 and worse PFS in a 2nd46
Pro/Pro → worse OS on subgroup analysis in a third study45
309G/G → worse OS in early stage [AHR 1.6; p=0.04] 50
309G/- → worse OS in advanced disease [AHR 1.7;p=0.03 46
10 studies
4 Asian
6 Caucasian
n=81-425
GSTM1-null → shorter OS in two studies [RR of death 1.36]
52
& [AHR 4.1] 53
GSTT1-null → shorter OS in a single study [AHR 2.1;
p=0.01] 98. Similar trend in 2nd study but small numbers
(n=6) 5
GSTP1 114 Val/- → longer survival in one study [AHR 0.75;
p=0.037] compared to Ala114Ala 97
3
Supplementary Table 2A. Additional polymorphisms assessed in multiple studies
Pathway/Gene
Matrix Metalloproteinase 54,55,100
MMP1 1607 1G/2G ; MMP2
(C1306T, C735T ) ; MMP3
(1171 5A/6A, A706G,
Glu45Lys) ; MMP7 A181G
MMP9 (C1562T, Pro574Arg,
Arg279Gln, Arg668Gln)
MMP12 (A79G; A1082G)
FGFR 101,102
FGFR4 Gly388Arg
Studies
Comment: Positive Findings
3 studies
1 Asian;
2 Caucasian
n=90 - 561
Two large studies assessed multiple SNPs 54,55.
MMP12 1082G/- alleles → worse OS in stage I NSCLC
[AHR 1.94; p=0.002] compared to A/A 54
MMP9 279 Gln/Gln → worse OS compared to Arg/- [HR
1.6; p=0.023] in a large Asian study 55
MMP2 -735C/C → worse prognosis than T/- alleles in a
smaller study [RR of death 2.6; p=0.05] 100
2 studies
Caucasian
n=274, 619
Arg/- → poorer OS in a single study (adenocarcinoma) [HR
1.6; p=0.008] compared to Gly/Gly 102;
Arg/- → no association in the larger study (SCLC+NSCLC)
Irinotecan Metabolism 56,57,103-105
UGT1A7 (*1,*2,*3,*4)
3 studies
UGT1A1 (*6,*28,*60)
2 Asian;
UGT1A16/7; UGT1A9*22
1 Caucasian
n=47-118
ABCB1 (G2677T/A, C1236T,
1 study
C3435T); ABCC2 (-C24T,
Asian; n=107
G1249A, C3972T)
SLCO1B1 G11187A SLCO1B1 1 study
A388G SLCO1B1 T521C
Asian; n=81
Vitamin D Receptor58,59
VDR Cdx-2 G/A
2 studies
VDR Fokl C/T
Caucasian
VDR Bsml C/T
n=294, 373
Folate Metabolism 60,61,106,107
MTHFR (Ala222Val,
Arg594Gln)
MTHFS Thr202Ala
MTRR Ser175Leu
(14 SNPS genotyped)
MTHFR C677T
MTHFR A1289C
TS VNTR H/- vs L/L
VEGF 62
VEGF (G405C, C936T,
T460C)
L-myc 63,64,108-111
L-myc Ser362Thr
L-mycEcoR1 RFLP
CYP 65-67
CYP2E1;
CYP1A1
CYP2D6*4; CYP3AP1*3;
CYP3A5*3; CYP2C19*2
CYP2C19*3; CYP2D6*2
1 study
Caucasian
n=619
3 studies
1 Asian
2 Caucasian n=127
- 295
UGT1A1*6 /6→ shorter PFS (p=0.001) and OS (p=0.17) in
a single Asian study (irinotecan treated) 56
No association with other SNPs and survival OR response in
irinotecan treated patients103,104.
ABCC2 24T/T and 3972T/T → higher RR (p= 0.31 and 0.05)
and longer PFS (p=0.01 and 0.02) than ABCC2 24 C/- and
3972 C/- 57
SLCO1B1 521C/- → higher incidence of Grade 4
neutropenia (p=0.008) 105. No association with response.
Early stage (Squamous Cell):VDR Cdx-2 A/- → better
survival [AHR 0.56; p=0.05] Combined “protective”
genotypes and A-C-T haplotype better OS 59
Advanced stage: VDR Fokl T/-, and G-T-C haplotype →
worse survival 58
Val222Val → shorter OS in SCLC only [HR 1.92 (1.03.58)] compared to Ala222Ala
Arg594Gln → longer OS in overall population [HR 0.68
(0.46-1.0)] compared to Arg594Arg.
Thr202Ala and Ser175Leu variant carriers → shorter OS in
NSCLC 60
C677T → no association with OS in two studies 106,107
T677T → better PFS than C/T or C/C on univariate analysis
in a third study (p=0.03) 61
TS L-group →longer OS only in combination with stage I
and MTHFR C-group (p=0.03) 107.
1 study
Caucas; n=462
VEGF 405 C/- → better 5year OS [AHR 0.70; p=0.008].
6 studies
3 Asian; 3 Caucas
n=83-252
L-mycEcoR1 RFLP S allele → shorter OS in one Asian
study64, longer OS in a second Asian study 63and no
association in two Caucasian studies 108,111
2 studies
Mixed; n=87
Asian; n=232
1 study
Asian; n=59
CYP2E1 wild type → better 5 year survival (p=0.02) 66
CYP1A1 non-susceptible homozygous → better OS in
advanced NSCLC (p=0.005)65
Treatment with Vinorelbine 67
CYP2D6*4 C/C (p=0.02) and CYP3AP1 A/A → better RR
(p=0.004)
CYP3A4*53 G/G → worse RR (p=0.004)
4
Supplementary Table 3A. Polymorphisms assessed in single studies
Pathway/Gene
TRIT1110
TRIT1 Phe202Leu
Inflammatory 112
TGF-β codon (10T/C, G25C); IL-6 G174C;
IL-10 (G1082A, C592A,C819T);
IFN-γ T874A; TNFα G308A
IGF 113
3’UTR IGF2R-A2/B2
Immune 114
MBL2 Y/X -289G>C; MBL L/H -618G>G;
MBL A/D Exl -34C>T; MBL A/B Ex 127G>A; MBL A/C Ex1 -18G>A
Others 61,89,93,115-120
KRAS2 Rsal A1/A2; PTHLH VNTR;
CDKN1B Val/Gly; M4(BstXI; StuI)
LRMP (Val141Leu; Ser197Cys)
CASC1 (rs12367971, rs10842496,
rs10842501,rs10842502)
Polysomy 7
MUC1 VNTR LS
PDCD5 rs1862214 C/G
FAS G1377A; FAS A670G; FASL C844T
DCK C3122T; DCTD T315C; POLA2
G1747A; S28A1 (419 Ins/Del, G565A,
C709A, G1368A, C1528T, G1561A); S28A2
(C65T, C225A); S28A3 A338G; TYMS
(1002R/3R, G58C, 15705Ins/Del)
GGH C452T; SLC 19A1 G80A; TS 5UTR
T/R; TS 5UTR 3C/G
CCND1 A870G
CDKN1A (p21 codon) 31Ser31Arg
Studies
Comment : Positive Findings
1(+ replication )
Predominantly
Caucasian
n=246,335
Leu allele → worse OS in Italian group
(adenocarcinoma) [HR 1.7; p=0.04)].
Leu allele → better OS in Norway group: [HR
0.5; p=0.02].
1 study
Caucasian; n=44
TGF-β T/T → better OS compared to C/C
(p=0.01).
1 study
Caucas; n=103
A2/B2 → worse OS (p=0.05) and +ve synergistic
effect with p53 inactivation.
1 study
Mixed; n=731
MBL2 X/- → improved survival in Caucasians,
p=0.001.
MBL2 LXA haplotype → improved survival.
1 study
Caucas; n=213
1 study
Caucasian
n=361
1 study
Caucas; n=82
1 study
Asian; n=56
1 study
Caucas; n=254
1 Study
Asian; n=338
1 Study
Asian; n=53
KRAS2 A2/- → better survival (p=0.008).
PTHLH allele2 → worse survival (p=0.03) 116
LRMP 141 Val/Val → better OS in <65years
(p=0.005) 117
No association with OS in overall population.
Treatment with Gefitinib:
High Polysomy 7 → better OS (p=0.004) 115
LL → worse OS only in adenocarcinoma
compared to S/- (p=0.11) 118
G/- → worse survival [HR 1.8, p=0.003)
compared to C/C 120
FAS 670G/- → worse OS than AA [HR 1.5,
p=0.047] 119
S28A2 65 T/- → independently associated with
improved OS [HR 0.3, p=0.002] 89
1 Study
Asian; n=127
1 Study
Caucas; n=244
1 Study
Mixed; n=155
No significant associations with PFS or toxicity 61
GG → better response to platinum compared to
A/- (p=0.04). No association with survival 121
Ser/Ser shorter survival compared to Ser/Arg or
Arg/Arg (p=0.097) 122
Abbreviations Tables1A-3A: Caucas: Caucasian; DFS: disease-free survival; AHR: adjusted hazard ratio; OS:
overall survival; RR: response rate; GI: gastrointestinal; gem: gemcitabine; tox: toxicity; PFS: progression-free
survival; ECOG PS: European Cooperative Oncology Group Performance Status; SCC: squamous cell
carcinoma; NSCLC: non-small cell lung cancer; SCLC: small cell lung cancer. *Haplotype.
References 1-81 are found in the main text and 82-122 are found in the supplemental text as supplementary
references. Supplementary Tables 1B,2B,3B show the RefSNP identifiers of the corresponding polymorphisms
in Tables 1A,2A,3A.
5
Supplementary Table 1B. Sequence variants and their RefSNP corresponding to
Supplementary Table 1A
Gene
SNP
DNA Synthesis / Repair
XRCC1
Arg399Gln
Arg194Trp
Arg280His
RefSNP
ERCC1
C118T
C8092A
G262T
T433C
C4855T
rs11615
rs3212986
rs2298881
rs3212930
rs3212961
XPD
Asp312Asn
Lys751Gln
C156A
Asp711Asp
rs1799793
rs13181
rs238406
rs1052555
RRM1
-A37C
-C524T
T756C
C269A
A67T
A60G
Asn148Glu
N/A
N/A
N/A
N/A
rs6966
rs664143
rs1130409
3435C/T
G2677T
Lys27Gln
A79C
C435T
gIVS12-6T/C
A23G
His46His
His1104Asp
rs1045642
rs2032582
rs2072671
rs2072671
rs1048977
rs2303428
rs1800975
rs1047768
rs17655
1(CA)nS/L
-G216T
-A191C
D994D
C2982T
G2607A
C421A
G34A
N/A
rs712829
rs712830
rs2293347
rs2293347
rs1050171
rs2231142
rs2231137
C211T
G3890A
C3942T
G565A
N/A
rs11568591
rs2277624
rs2290272
iASPP
ATM
APE1
MDR
CDA
hMSH2
XPA
XPG
EGFR
EGFR
ABCG2
ABCC3
CNT1
rs25487
rs1799782
rs25489
Gene
p53
P53
SNP
RefSNP
Arg72Pro
Intron 3
rs1042522
N/A
MDM2
MDM2
T309G
Glutathione S-transferase
GSTP1
Ile105Val
A/G
Ala114Val
γ-GCS
7/8
rs2279744
rs1695
N/A
rs1138272
N/A
N/A: not available
6
Supplementary Table 2B. Sequence variants and their RefSNP corresponding to
Supplementary Table 2A
Gene
SNP
Matrix Metalloproteinase
MMP1
1607 1G/2G
MMP2
C1306T
C735T
RefSNP
MMP3
1171 5A/6A
A706G
Glu45Lys
rs3025058
N/A
rs679620
A181G
C1562T
Pro574Arg
Arg279Gln
rs11568818
rs3918242
rs2250889
rs17576
Arg668Gln
A79G
A1082G
rs17577
N/A
rs652438
Ser362Thr
EcoRI RFLP
rs3134614
N/A
MMP7
MMP9
MMP12
L-myc
L-myc
FGFR
FGFR4
Gly388Arg
Irinotecan Metabolism
UGT1A1
*6
*28
*60
6/7
UGT1A7
*1
*2
*3
*4
UGT1A9
*22
ABCB1
T2677A
C1236T
C3435T
rs1799750
rs243865
rs2285052
rs351855
Gene
Vitamin D Receptor
VDR
SNP
RefSNP
Cdx-2G/A
Fokl C/T
Bsml C/T
N/A
N/A
N/A
Ala222Val
Arg594Gln
A1289C
rs1801133
rs2274976
rs1801131
Ser175Leu
Thr202Ala
VNTR H/L/L
rs1532268
rs8923
N/A
N/A
N/A
*4
*2
N/A
N/A
rs3892097
rs16947
CYP2C19
*2
*3
rs4244285
rs4986893
CYP3A5
CYP3AP1
*3
*3
rs776746
N/A
Folate Metabolism
MTHFR
MTRR
MTHFS
TS
CYP
CYP2E1
CYP1A1
CYP2D6
rs4148323
N/A
N/A
N/A
N/A
N/A
N/A
N/A
N/A
rs2032582
rs1128503
rs10456642
ABCC2
-C24T
G1249A
C3972T
rs717620
rs2273697
rs3740066
SLCO1B1
G11187A
A388G
T521C
rs4149015
rs2306283
rs4149056
N/A: not available
7
Supplementary Table 3B. Sequence variants and their RefSNP corresponding to
Supplementary Table 3A
Gene
TRIT1
TRIT1
VEGF
VEGF
Inflammatory
TGF-b
IL-6
IL-10
TNFa
IFN-γ
IGF
IGF2R
Immune
MBL2
MBL
Others
KRAS2
PTHLH
CDKN1B
M4
LRMP
CASC1
Chr7
MUCI
SNP
RefSNP
Phe202Leu
rs3738671
Gene
Others
FAS
G405C
C936T
T460C
rs2010963
rs3025039
rs833061
FASL
NQO1
STK15
codon 10T/C
codon 25G/C
G174C
G1082A
C592A
819C/T
G308A
T874A
rs1800470
rs1800471
rs1800795
rs1800896
rs1800872
rs1800871
rs1800629
rs2430561
PDCD5
CDA
3'UTR A2/B2
N/A
Y/X -289G>C
L/H -618G>G
A/D ExI -34C>T
A/B ExI -27G>A
A/C Exl -18G>A
rs7096206
rs11003125
rs5030737
rs1800450
rs1800451
RsaI A1/A2
VNTR
Val/Gly
BstXI, StuI
Val141Leu
Ser197Cys
R33S
Intronic
Intronic
Intronic
Polysomy 7
VNTR LS
N/A
N/A
N/A
N/A
rs7969931
rs1908946
rs10842496
rs12367971
rs10842501
rs10842502
N/A
N/A
DCK
DCTD
POLA2
S28A1
S28A2
S28A3
TYMS
GGH
SLC19A1
TS
ABCC3
RAD23
CCND1
CDKN1A
N/A: not available
SNP
RefSNP
G670A
G1377A
C834T
T/C
T31A
G57A
C/G
A79C
C435T
C3122T
T315C
G1747A
416Ins/Del
G565A
C709A
G1368A
C1528T
G1561A
C65T
C225A
A338G
1002R/3R
G58C
15705Ins/Del
C452T
G80A
5UTR T/R
5UTR 3C/G
C211T
G3809A
C3942T
C/T
A870G
Ser31Arg
rs1800682
rs2234767
rs763110
rs1800566
rs2273535
rs1047972
rs1862214
rs2072671
rs1048977
rs3775289
N/A
N/A
rs17215836
rs2290272
rs8187758
rs2242048
rs2242047
rs2242046
rs61637002
rs1060896
rs10868138
N/A
N/A
N/A
N/A
rs1051266
N/A
N/A
N/A
rs11568591
rs2277624
rs1805329
rs603965
rs1801270
8
SUPPLEMENTARY REFERENCES:
82.
Yu D, Zhang X, Liu J, et al: Characterization of functional excision repair
cross-complementation group 1 variants and their association with lung cancer risk and
prognosis. Clin Cancer Res 14:2878-86, 2008
83.
Camps C, Sarries C, Roig B, et al: Assessment of nucleotide excision repair
XPD polymorphisms in the peripheral blood of gemcitabine/cisplatin-treated advanced nonsmall-cell lung cancer patients. Clin Lung Cancer 4:237-41, 2003
84.
Wu W, Zhang W, Qiao R, et al: Association of XPD polymorphisms with
severe toxicity in non-small cell lung cancer patients in a Chinese population. Clin Cancer
Res 15:3889-95, 2009
85.
Bepler G, Zheng Z, Gautam A, et al: Ribonucleotide reductase M1 gene
promoter activity, polymorphisms, population frequencies, and clinical relevance. Lung
Cancer 47:183-92, 2005
86.
Feng JF, Wu JZ, Hu SN, et al: Polymorphisms of the ribonucleotide reductase
M1 gene and sensitivity to platin-based chemotherapy in non-small cell lung cancer. Lung
Cancer, 2009
87.
Isla D, Sarries C, Rosell R, et al: Single nucleotide polymorphisms and
outcome in docetaxel-cisplatin-treated advanced non-small-cell lung cancer. Ann Oncol
15:1194-203, 2004
88.
Kim SO, Jeong JY, Kim MR, et al: Efficacy of gemcitabine in patients with
non-small cell lung cancer according to promoter polymorphisms of the ribonucleotide
reductase M1 gene. Clin Cancer Res 14:3083-8, 2008
89.
Soo RA, Wang LZ, Ng SS, et al: Distribution of gemcitabine pathway
genotypes in ethnic Asians and their association with outcome in non-small cell lung cancer
patients. Lung Cancer 63:121-7, 2009
90.
Feng J, Sun X, Sun N, et al: XPA A23G polymorphism is associated with the
elevated response to platinum-based chemotherapy in advanced non-small cell lung cancer.
Acta Biochim Biophys Sin (Shanghai) 41:429-35, 2009
91.
Hsu HS, Lee IH, Hsu WH, et al: Polymorphism in the hMSH2 gene (gISV126T > C) is a prognostic factor in non-small cell lung cancer. Lung Cancer 58:123-30, 2007
92.
Sohn JW, Lee SY, Lee SJ, et al: MDR1 polymorphisms predict the response to
etoposide-cisplatin combination chemotherapy in small cell lung cancer. Jpn J Clin Oncol
36:137-41, 2006
93.
Muller PJ, Dally H, Klappenecker CN, et al: Polymorphisms in ABCG2,
ABCC3 and CNT1 genes and their possible impact on chemotherapy outcome of lung cancer
patients. Int J Cancer 124:1669-74, 2009
94.
Sasaki H, Endo K, Takada M, et al: EGFR polymorphism of the kinase
domain in Japanese lung cancer. J Surg Res 148:260-3, 2008
95.
Sasaki H, Okuda K, Takada M, et al: A novel EGFR mutation D1012H and
polymorphism at exon 25 in Japanese lung cancer. J Cancer Res Clin Oncol 134:1371-6,
2008
96.
Booton R, Ward T, Heighway J, et al: Glutathione-S-transferase P1 isoenzyme
polymorphisms, platinum-based chemotherapy, and non-small cell lung cancer. J Thorac
Oncol 1:679-83, 2006
97.
Lu C, Spitz MR, Zhao H, et al: Association between glutathione S-transferase
pi polymorphisms and survival in patients with advanced nonsmall cell lung carcinoma.
Cancer 106:441-7, 2006
9
98.
Sreeja L, Syamala V, Hariharan S, et al: Glutathione S-transferase M1, T1 and
P1 polymorphisms: susceptibility and outcome in lung cancer patients. J Exp Ther Oncol
7:73-85, 2008
99.
Yang P, Yokomizo A, Tazelaar HD, et al: Genetic determinants of lung cancer
short-term survival: the role of glutathione-related genes. Lung Cancer 35:221-9, 2002
100. Rollin J, Regina S, Vourc'h P, et al: Influence of MMP-2 and MMP-9
promoter polymorphisms on gene expression and clinical outcome of non-small cell lung
cancer. Lung Cancer 56:273-80, 2007
101. Matakidou A, El Galta R, Rudd MF, et al: Further observations on the
relationship between the FGFR4 Gly388Arg polymorphism and lung cancer prognosis. Br J
Cancer 96:1904-7, 2007
102. Spinola M, Leoni V, Pignatiello C, et al: Functional FGFR4 Gly388Arg
polymorphism predicts prognosis in lung adenocarcinoma patients. J Clin Oncol 23:7307-11,
2005
103. Ando M, Ando Y, Sekido Y, et al: Genetic polymorphisms of the UDPglucuronosyltransferase 1A7 gene and irinotecan toxicity in Japanese cancer patients. Jpn J
Cancer Res 93:591-7, 2002
104. Font A, Sanchez JM, Taron M, et al: Weekly regimen of irinotecan/docetaxel
in previously treated non-small cell lung cancer patients and correlation with uridine
diphosphate glucuronosyltransferase 1A1 (UGT1A1) polymorphism. Invest New Drugs
21:435-43, 2003
105. Han JY, Lim HS, Shin ES, et al: Influence of the organic anion-transporting
polypeptide 1B1 (OATP1B1) polymorphisms on irinotecan-pharmacokinetics and clinical
outcome of patients with advanced non-small cell lung cancer. Lung Cancer 59:69-75, 2008
106. Alberola V, Sarries C, Rosell R, et al: Effect of the methylenetetrahydrofolate
reductase C677T polymorphism on patients with cisplatin/gemcitabine-treated stage IV nonsmall-cell lung cancer. Clin Lung Cancer 5:360-5, 2004
107. Takehara A, Kawakami K, Ohta N, et al: Prognostic significance of the
polymorphisms in thymidylate synthase and methylenetetrahydrofolate reductase gene in
lung cancer. Anticancer Res 25:4455-61, 2005
108. Fong KM, Kida Y, Zimmerman PV, et al: MYCL genotypes and loss of
heterozygosity in non-small-cell lung cancer. Br J Cancer 74:1975-8, 1996
109. Shih CM, Kuo YY, Wang YC, et al: Association of L-myc polymorphism
with lung cancer susceptibility and prognosis in relation to age-selected controls and stratified
cases. Lung Cancer 36:125-32, 2002
110. Spinola M, Falvella FS, Galvan A, et al: Ethnic differences in frequencies of
gene polymorphisms in the MYCL1 region and modulation of lung cancer patients' survival.
Lung Cancer 55:271-7, 2007
111. Tefre T, Borresen AL, Aamdal S, et al: Studies of the L-myc DNA
polymorphism and relation to metastasis in Norwegian lung cancer patients. Br J Cancer
61:809-12, 1990
112. Colakogullari M, Ulukaya E, Yilmaztepe Oral A, et al: The involvement of
IL-10, IL-6, IFN-gamma, TNF-alpha and TGF-beta gene polymorphisms among Turkish
lung cancer patients. Cell Biochem Funct 26:283-90, 2008
113. Kotsinas A, Evangelou K, Sideridou M, et al: The 3' UTR IGF2R-A2/B2
variant is associated with increased tumor growth and advanced stages in non-small cell lung
cancer. Cancer Lett 259:177-85, 2008
114. Pine SR, Mechanic LE, Ambs S, et al: Lung cancer survival and functional
polymorphisms in MBL2, an innate-immunity gene. J Natl Cancer Inst 99:1401-9, 2007
10
115. Buckingham LE, Coon JS, Morrison LE, et al: The prognostic value of
chromosome 7 polysomy in non-small cell lung cancer patients treated with gefitinib. J
Thorac Oncol 2:414-22, 2007
116. Manenti G, De Gregorio L, Pilotti S, et al: Association of chromosome 12p
genetic polymorphisms with lung adenocarcinoma risk and prognosis. Carcinogenesis
18:1917-20, 1997
117. Manenti G, Galbiati F, Pettinicchio A, et al: A V141L polymorphism of the
human LRMP gene is associated with survival of lung cancer patients. Carcinogenesis
27:1386-90, 2006
118. Mitsuta K, Yokoyama A, Kondo K, et al: Polymorphism of the MUC1 mucin
gene is associated with susceptibility to lung adenocarcinoma and poor prognosis. Oncol Rep
14:185-9, 2005
119. Park JY, Lee WK, Jung DK, et al: Polymorphisms in the FAS and FASL
genes and survival of early stage non-small cell lung cancer. Clin Cancer Res 15:1794-800,
2009
120. Spinola M, Meyer P, Kammerer S, et al: Association of the PDCD5 locus with
lung cancer risk and prognosis in smokers. J Clin Oncol 24:1672-8, 2006
121. Gautschi O, Hugli B, Ziegler A, et al: Cyclin D1 (CCND1) A870G gene
polymorphism modulates smoking-induced lung cancer risk and response to platinum-based
chemotherapy in non-small cell lung cancer (NSCLC) patients. Lung Cancer 51:303-11, 2006
122. Shih CM, Lin PT, Wang HC, et al: Lack of evidence of association of
p21WAF1/CIP1 polymorphism with lung cancer susceptibility and prognosis in Taiwan. Jpn
J Cancer Res 91:9-15, 2000
11