Table S1 Spontaneous incidence of lung tumors amonginbred mouse strains

Strains / Incidence (%) / # of mice
AKR/J / 0 / 71
C57L/J / 0 / 101
CE/J / 0 / 17
DBA/2J / 0 / 118
NZB/BlNJ / 0 / 535
129S1/SvImJ / 1 / 149
C57BL/10J / 3 / 93
C57BL/6J / 3 / 729
C57BR/cdJ / 3 / 30
DBA/1J / 3 / 30
P/J / 3 / 30
LP/J / 5 / 128
SJL/J / 5 / 30
C3H/HeJ / 9 / 408
CBA/J / 17 / 681
RF/J / 26 / 115
NZO/B1 / 31 / 127
BALB/cByJ / 33 / 901
RIIIS/J / 34 / 112
FVB/NJ / 36 / 121
O20 / 41 / 136
MA/MyJ / 42 / 30
SWR/J / 47 / 437
A/J / 82 / 182
Mean / 17.7 / 221.3

Note: table was modified from the study of Manenti et al. (Carcinogenesis, 2005: 26, 875-82). Bold are strains overlapped between spontaneous lung tumor GWAS and expression QTL experiments.

Table S2 Primer sequences for quantitative RT-PCR analysis

Mouse Xrn2 / forward / 5’-TCTGAATTTGAAAAGGCACAA-3’
reverse / 5’-CCACTTGCAGCTGGGAAAAC-3’
Human XRN2 / forward / 5’-AGGAATTAAGCGAAAAGCAGAAGA-3’
reverse / 5’-TCCAGCCAGCTTCCCATAAC-3’
Mouse Involucrin / forward / 5’-AGCTTCCAAGATGTCCCATCA-3’
reverse / 5’-TCTTGAGAGGTCCCTGAACCA-3’
Human Involucrin / forward / 5’-ATACCCATCAGGAGCAAATGAAA-3’
reverse / 5’-AGCTCGACAGGCACCTTCTG-3’
Mouse beta-actin / forward / 5’-CAAGAGATGGCCAGGGCTGCT-3’
reverse / 5’-TCCTTCTGCATCCTGTCGGCA-3’
Human beta-actin / forward / 5’-CAAGAGATGGCCAGGGCTGCT-3’
reverse / 5’-TCCTTCTGCATCCTGTCGGCA-3’

Table S3XRN2 expression in various human cancers*

Probe ID / Source† / Class 1‡ / Class 2‡ / Mean 1§ / Mean 2§ / t-statistic** / P-Value / Q-Value / Pubmed ID
223002_s_at / 1 / Normal Brain (6) / Anaplastic Oligoastrocytoma (4)
Anaplastic Oligodendroglioma (23) / 0.462 / 1.063 / -8.505 / 1.09E-05 / 4.54E-04 / Top of Form
16357140
233878_s_at / 1 / Normal Brain (6) / Anaplastic Oligoastrocytoma (4)
Anaplastic Oligodendroglioma (23) / 0.019 / 0.743 / -5.650 / 3.11E-04 / 5.23E-03 / Top of Form
16357140Bottom of Form
223002_s_at / 1 / Normal Brain (23)Bottom of Form / Astrocytoma (26) / 0.495 / 0.782 / -4.998 / 5.64E-06 / 1.29E-04 / 16616334
233878_s_at / 1 / Normal Brain (23)Bottom of Form / Astrocytoma (26) / 0.476 / 0.726 / -4.560 / 1.92E-05 / 3.55E-04 / 16616334
IMAGE:364840 / 5 / Normal Brain (4) / Glioblastoma (31) / -1.149 / -0.304 / -5.676 / 2.13E-03 / 2.60E-02 / 16204036
233878_s_at / 1 / Top of Form
Normal Brain (23)Bottom of Form / Glioblastoma Multiforme (77) / 0.476 / 0.931 / -10.096 / 7.67E-15 / 4.02E-13 / 16616334
223002_s_at / 1 / Normal Brain (23)Bottom of Form / Glioblastoma Multiforme (77) / 0.495 / 0.938 / -8.357 / 2.86E-10 / 5.78E-09 / 16616334
233878_s_at / 1 / Normal Brain (23) / Oligodendroglioma (50) / 0.476 / 0.719 / -5.390 / 7.56E-07 / 1.37E-05 / 16616334
223002_s_at / 1 / Normal Brain (23)Bottom of Form / Oligodendroglioma (50) / 0.495 / 0.744 / -4.464 / 3.00E-05 / 3.42E-04 / 16616334
223002_s_at / 1 / Normal Breast (15) / Invasive Ductal Breast Carcinoma (7) / 1.138 / 0.875 / 3.449 / 2.02E-05 / 7.58E-02 / 17914389
233878_s_at / 1 / Normal Bone Marrow (22) / Smoldering Mulitple Myeloma (12) / 0.599 / 1.002 / -7.017 / 7.27E-08 / 1.31E-05 / 17023574
223002_s_at / 1 / Normal Bone Marrow (22) / Smoldering Mulitple Myeloma (12) / -0.102 / 0.699 / -6.853 / 1.09E-07 / 1.67E-05 / 17023574
223002_s_at / 1 / Top of Form
Normal (8)Bottom of Form / Top of Form
Cervical Cancer (20)Bottom of Form / 0.097 / 1.044 / -5.946 / 2.66E-05 / 4.14E-04 / 17510386
233878_s_at / 1 / Top of Form
Normal (8)Bottom of Form / Top of Form
Cervical Cancer (20)Bottom of Form / -0.387 / 0.199 / -4.334 / 1.07E-04 / 1.10E-03 / 17510386
IMAGE:2821246 / 4 / Top of Form
Normal Colon (12)Bottom of Form / Colorectal Carcinoma (18) / -0.538 / -0.026 / -5.077 / 1.28E-05 / 5.18E-04 / 16542501
IMAGE:2821246 / 4 / Top of Form
Normal Colon (12)Bottom of Form / Colorectal Carcinoma (18) / -0.535 / -0.052 / -4.076 / 1.76E-04 / 3.61E-03 / 16542501
233878_s_at / 1 / Top of Form
Normal (14)Bottom of Form / Top of Form
Head and Neck Cancer (42)Bottom of Form / -0.363 / 0.180 / -4.728 / 1.31E-05 / 5.20E-04 / 17510386
223002_s_at / 1 / Top of Form
Normal (14)Bottom of Form / Top of Form
Head and Neck Cancer (42)Bottom of Form / 0.357 / 1.029 / -5.257 / 2.04E-05 / 7.04E-04 / 17510386
IMAGE:364840 / 5 / Top of Form
Normal Lung (6)Bottom of Form / Lung Adenocarcinoma (40) / -0.639 / -0.104 / -3.852 / 1.21E-03 / 2.32E-02 / 11707590
233878_s_at / 2 / Top of Form
Normal Prostate (8)Bottom of Form / Prostate Adenocarcinoma (27) / 0.515 / 0.876 / -3.218 / 3.51E-03 / 4.82E-02 / Top of Form
12873976Bottom of Form
NM_012255 / 3 / Top of Form
Normal Testis (3)Bottom of Form / Embryonal Carcinoma (11) / -1.712 / 0.095 / -3.684 / 1.95E-03 / 2.27E-02 / 15994931
NM_012255 / 3 / Top of Form
Normal Testis (3)Bottom of Form / Top of Form
Seminoma (3)Bottom of Form / -1.712 / 0.404 / -7.197 / 6.36E-03 / 1.18E-01 / 15994931
IMAGE:364840 / 5 / Normal Testis (14) / Seminoma (23) / -0.366 / 0.097 / -5.950 / 6.50E-07 / 1.27E-05 / 14595015

*Expression data were retrieved from the ONCOMINE Research Platform ( as of 04/29/2009).

† 1, Human U133 Plus 2.0 Array; 2, Human U133B Array; 3, Ref_Seq_NM; 4, NIH_MGC_7; 5, Soares_fetal_heart_NbHH19W.

‡Numbers in parentheses are sample size of tissues.

§Arithmetic mean of expression in tissues from Class 1and Class 2 after normalization.

**Negative t-statistic indicates that expression in normal tissues is lower than tumor tissues, i.e. Xrn2 is overexpressed in tumor tissues.

Table S4 Associations of XRN2 with human lung cancer in the IARC lung GWAS dataset

dbSNP* / Chr. / Pos. (bp) / Ma / MAF / Co-dominant model / Co-dominant model
Control / Case / Unadjusted / Adj. for age, sex, country
OR / 95%CI / P-value / OR / 95%CI / P-value
rs1359761 / 20 / 21241884 / T / 0.2772 / 0.2997 / 1.12 / 1.02-1.22 / 0.0204 / 1.11 / 1.01-1.23 / 0.0257
rs202841 / 20 / 21264154 / A / 0.0871 / 0.0938 / 1.09 / 0.94-1.26 / 0.2758 / 1.07 / 0.92-1.24 / 0.3802
rs6035850 / 20 / 21273711 / C / 0.3258 / 0.3407 / 1.07 / 0.98-1.17 / 0.1421 / 1.07 / 0.98-1.18 / 0.1264
rs1958122 / 20 / 21277780 / C / 0.2761 / 0.2978 / 1.11 / 1.01-1.22 / 0.0253 / 1.11 / 1.01-1.22 / 0.0341
rs2025811 / 20 / 21283113 / C / 0.1473 / 0.1716 / 1.20 / 1.07-1.35 / 0.0019 / 1.21 / 1.07-1.36 / 0.0019
rs4497932 / 20 / 21290378 / C / 0.2758 / 0.2986 / 1.12 / 1.02-1.23 / 0.0186 / 1.12 / 1.01-1.23 / 0.0252
rs3848794 / 20 / 21291944 / A / 0.1898 / 0.2056 / 1.11 / 1.00-1.23 / 0.0619 / 1.11 / 1.00-1.24 / 0.0565
rs2296730 / 20 / 21315741 / A / 0.0524 / 0.0454 / 0.86 / 0.70-1.05 / 0.1388 / 0.88 / 0.72-1.09 / 0.242

* SNPs within XRN2 (chr20:21,231,942 to 21,318,463 bp) were extracted from the IARC lung cancer study which contained 317,139 SNPs in1,989 lung cancer cases and 2,625 controls from six central European countries (

Figure S1Genome-wide association of SNPs with Xrn2 expression in the lungs of inbred mice