Supplementary Table1.Primer sequences and restriction enzymes

Gene / Polymorphisms / Reference No. / Location / Primer / Restriction enzyme
TS / 2R or 3R VNTR in ER* / rs34743033 / ER (5'UTR) / Forward: GTGGCTCCTGCGTTTCCCCC
Backward:
GCTCCGAGCCGGCCACAGGCATGGCGCGG
G/C SNP in 3R / rs2273804 / 5'UTR / Forward:: GTGGCTCCTGCGTTTCCCCC / Hae III
Backward:
GCTCCGAGCCGGCCACAGGCATGGCGCGG
6 bp insertion(+)/
deletion(-) / rs16430 / 3'UTR / Forward: CAAATCTGAGGGAGCTGAGT / Dra I
Backward: CAGATAAGTGGCAGTACAGA
MTHFR / C677T / rs1801133 / Exon4 / Forward: GCACTTGAAGGAGAAGGTGTC / Taq I
Backward: AGGACGGTGCGGTGAGAGTG
A1298C / rs1801131 / Exon7 / Forward: GGAGGAGCTGACCAGTGCAG / Fnu4H I
Backward: CCACTCCAGCATCACTCACTT
ERCC1 / T19007C / rs11615 / Exon4 / Forward: CATCCCTATTGATGGCTTCTGCCC / BsrD I
Backward: GACCATGCCCAGAGGCTTCTCATAG
C8092A / rs3212986 / 3'UTR / Forward: CAGAGACAGTGCCCCAAGAG / Mbo II
Backward: GGGCACCTTCAGCTTTCTTT
XPD / C22541A / rs238406 / Exon6 / Forward: CACACCTGGCTCATTTTTGTAT / Tfi I
Backward: TCATCCAGGTTGTAGATGCCA
G23591A / rs1799793 / Exon10 / Forward:
CTGTTGGTGGGTGCCCGTATCTGTTGGTCT / Sty I
Backward:
(TAATA)TCGGGGCTCACCCTGCAGCACTTCCT
A35931C / rs13181 / Exon23 / Forward: GCCCGCTCTGGATTATACG / Pst I
Backward: CTATCATCTCCTGGCCCCC
XRCC1 / G23885A / rs25487 / Exon10 / Forward: TTGTGCTTTCTCTGTGTCCA / Msp I
Backward: TCCTCCAGCCTTTTCTGATA
C21935T / rs1799782 / Exon6 / Forward:GACCTTAGAAGGTGACAGTGACCAA / Pvu II
Backward: TCACTCAGGACCACGTTGT
G23098A / rs25489 / Exon9 / Forward: GTCTTCTCCAGTGCCAGCTC / Rsa I
Backward: AGCCACTCAGCACCACTACC
AGXT / A1142G / rs4426527 / Exon10 / Forward: GCCAAGAGCTGTCACAAA / SNapShot
Backward: GACGCTCCTGCAATCTG
Genotyping: GGAGAGACATCGTCAGCTACGTCAT
C154T / rs34116584 / Exon1 / Forward: TACCGACCTGAGCTGGATC / SNapShot
Backward: CATCCAGGCCTTCCTTCA
Genotyping: GGAGAGGGGCTTGAGCAGGGCCTTG
ABCC2 / C3972T / rs3740066 / Exon28 / Forward: ATCCACCAATCCTCACCT / SNapShot
Backward: ATCTGTGGGTGGGAACAT
Genotyping: CTCCACCTACCTTCTCCATGCTACC
C-24T / rs717620 / Exon1 / Forward: CAGGAAACAGCTATGACCactggtgagtctccctgtcc / SNapShot
Backward: TGTAAAACGACGGCCAGTaaggcaattttgcgactagc
Genotyping:
GCATGATTXCTGGACTGCGTCTGGAAY
GSTP1 / A313G / rs1695 / Exon5 / Forward: CTCTATGGGAAGGACCAGCA / BsmA I
Backward: TGAGGGCACAAGAAGCCCCT
GSTT1 / Null genotype / - / Forward: TTCCTTACTGGTCCTCACATCTC / -
Backward: TCACCGGATCATGGCCAGCA
GSTM1 / Null genotype / - / Forward: GAACTCCCTGAAAAGCTAAAGC / -
Backward: GTTGGGCTCAAATATACGGTGG

Abbreviations: ERCC1, excision repair cross complementing group 1; GST, glutathione S-transferase; MTHFR, methylenetetrahydrofolate reductase; TS, thymidylate synthase; UTR, untranslated region; XPD, xeroderma pigmentosum group D; XRCC1, X-ray cross complementing group 1; XRCC3, X-ray cross complementing protein 3

*Variable number of tandem repeats (VNTR) polymorphism is a double repeat (2R) or triple repeat (3R) of 28-bp sequence in TS 5' UTR

Supplementary Table 2. Genotype frequencies (n = 292)

Genotypes / Overall frequency
No. of patients / %
TS-5´UTR
2R/2R / 5 / 1.7
2R/3R / 90 / 30.8
2R/4R / 3 / 1.0
3R/3R / 191 / 65.4
3R/4R / 3 / 1.0
TS-3´UTR
-6/-6 / 143 / 49.0
-6/+6 / 120 / 41.1
+6/+6 / 29 / 9.9
TS-5´UTR*
2R/2R,2R/3C,3C/3C / 98 / 34.3
2R/3G,3C/3G,3G/3G / 188 / 65.7
MTHFR 677C>T
CC / 93 / 31.8
CT / 136 / 46.6
TT / 62 / 21.2
MTHFR 1298A>C
AA / 210 / 71.9
AC / 70 / 24.0
CC / 11 / 3.8
ERCC1 8092C>A
AA / 22 / 7.5
CA / 109 / 37.3
CC / 161 / 55.1
ERCC1 19007TC
AA / 20 / 6.8
AG / 99 / 33.9
GG / 172 / 58.9
XPD 35931A>C
CC / 1 / 0.3
AC / 28 / 9.6
AA / 262 / 89.7
XPD 22541C>A
CC / 87 / 29.8
CA / 137 / 46.9
AA / 67 / 22.9
XPD 23591G>A
AG / 22 / 7.5
GG / 267 / 91.4
AA / 0 / 0
unknown / 3 / 1.0
XRCC1 23885G>A
AA / 21 / 7.2
GA / 131 / 44.9
GG / 139 / 47.6
XRCC1 21935C>T
CC / 132 / 45.2
CT / 131 / 44.9
TT / 28 / 9.6
XRCC1 23098G>A
AA / 2 / 0.7
GA / 43 / 14.7
GG / 246 / 84.2
AGXT 1142A>G
AA / 246 / 84.2
GA / 43 / 14.7
GG / 0 / 0
AGXT A54C>T
CC / 289 / 99.0
CT / 1 / 0.3
TT / 0 / 0
ABCC2 13241C>T
CC / 154 / 52.7
CT / 119 / 40.8
TT / 16 / 5.5
ABCC2-24T
CC / 160 / 54.8
CT / 113 / 38.7
TT / 14 / 4.8
GSTP1 I105V
AA / 215 / 73.6
AG / 65 / 22.3
GG / 11 / 3.8
GSTT1¶
present / 137 / 46.9
absent / 148 / 50.7
GSTM1
present / 153 / 52.4
absent / 132 / 45.2

*Analysis of the TS 5´ UTR variable number of tandem repeats (VNTR) polymorphism with G/C nucleotide change in 3R allele carriers

¶A genotype was defined as positive if at least one copy of the gene was present

Supplementary Table3.Comparison of genotypes frequencies in different ethnic groups

Gene / Polymorphisms / CHB+JPT vs. Korean (P) / CEU vs. Korean (P)
TS / 2R or 3R VNTR in ER / 0.268 / < 0.001
G/C SNP in 3R / 0.689 / < 0.001
6 bp insertion(+)/
deletion(-) / < 0.001 / < 0.001
MTHFR / C677T / 0.540 / 0.002
A1298C / 0.048 / < 0.001
ERCC1 / T19007C / 0.238 / < 0.001
C8092A / 0.693 / < 0.001
XPD / C22541A / 0.922 / 0.087
G23591A / 0.011 / < 0.001
A35931C / 0.086 / < 0.001
XRCC1 / G23885A / 0.453 / 0.146
C21935T / 0.163 / < 0.001
G23098A / 0.824 / 0.210
AGXT / A1142G / 0.163 / < 0.001
C154T / - / < 0.001
ABCC2 / C3972T / 0.646 / 0.06
C-24T / 0.296 / 0.101
GSTP1 / A313G / 0.428 / < 0.001
GSTT1 / Null / < 0.001
GSTM1 / Null / 0.395

Detailed frequency data are presented in Figure 1 and Supplementary Figure

1