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Table 1 Characteristics of the twenty-one studies included in systematic review

From: Single nucleotide polymorphisms and the risk of developing a second primary cancer among head and neck cancer patients: a systematic literature review and meta-analysis

First author, Year [Ref] Country Study design; Study period Number of HNC patients Follow-up, years a) mean (SD), b) median [IQR] Patients' age, years a) mean (SD); b) median [IQR]  Gender,
Male (%)
Ethnicity (%) Primary HNC site (%) Primary HNC stage (%) Number of patients with SPC (%) Site of SPC Chromosome Genes investigated SNP
Li F, 2010 [23] USA, Texas Cohort;1995–2007 1.271 HNC 2.2b) [0–11.8] at HNC 57.2 a);
at SPC 60.9 a)
75.6 Non-Hispanic white (85.4) oropharyx (45.2);
non-oropharynx (54.8)
I or II (25.9);
III e IV (74.1)
109 (8.6) 42 HNC; 38 other tobacco related (head & neck, esophagus, lung, bladder); 29 other non-tobacco related 17 p53 rs1042522
Wang J, 2010 [24] USA, Texas Case-control; 1991–1999 147 HNC SPC cases; 293 controls cases 2.3b;
controls 5.0b
61.15 a) (10.25) 79.55 Caucasian (96.1) larynx (47.6);
oralcavity (31.29);
pharynx (21.09)
I (59.2);
II (40.8)
147 (100) NR 1 RGS2; GS13; RGS8; GS11; RGS5; RGS3; RGS7 rs2179653; rs3795617; rs6670735; rs739999; rs11586945; rs3747813; rs6689169
Lee JJ, 2011 [35] USA, Texas Cohort;1991–1999 215 HNC NR 60.9 a) (10.57) 76.28 Caucasian (5.8) larynx (56.7);
oral (31.6);
pharynx (11.6)
I (66.1);
II (33.9)
76 (35.3) NR 9; 11 RXRA; JAK2; TNKS1BP1; MMP3; RAD54L; BCCIP; SLC31A1; GSTM5; TSC1; JAK2; CDK8; TSC1; FLT3; CA9; TSC1; MP21 rs3118570; rs1887427; rs3025090; rs12137934; rs6596428; rs11244664; rs2233913; rs11101992; rs7040593; rs2274471; rs1410280; rs3827665; rs9551427; rs1243872; rs11602501; rs739442; rs10901431
Li F, 2009 [37] USA, Texas Cohort; 1995–2007 1.384 HNC 2.2b) [0–11.8] at HNC 57.3 a);
at SPC 60.8 a)
76.1 Non-Hispanic white (83.8) oral cavity (32.7); oropharynx (45.1); hypopharynx/larynx (22.2) I or II (25.4);
III or IV (74.6)
110 (8.0) 77 tobacco related, 29 non-tobacco related, 4 both tobacco- and non-tobacco related 1 P73 G4C14-to-A4T14 (rs2273953 and rs1801173)
Zafereo, 2009 [39] USA, Texas Cohort; 1995–2006 1.376 HNC 2.2b) at HNC 57.3 a);
at SPC 60.8 a)
76.0 Non-Hispanic white (84.0) oral cavity (32.9);
oropharynx (44.9);
larynx/ hypopharynx (22.2)
I or II (25.5);
III or IV (74.5)
110 (8.0) 43 HNC; 38 tobacco-related; 29 non-tobacco related 9 ERCC1; XPA; XPC; XPD; XPG ERCC1 rs3212986 (C8092A); XPA rs1800975 (G23A); XPC Ala499Val (rs1799793); XPC Lys939Gln; XPD Asp312Asn (rs1799793); XPD Lys751Gln; XPG His1104Asp (rs17655)
Zafereo, 2009 [40] USA, Texas Cohort; 1995–2006 1.376 HNC 2.2b) at HNC 57.3a);
at SPC 60.8a)
76.0 Non-Hispanic white (84.0) oral cavity (32.9); oropharynx (44.9); larynx/hypopharynx (22.2) I or II (25.5);
III or IV (74.5)
110 (8.0) 43 HNC SPC; 38 tobacco-related; 29 non-tobacco related 1;
22
GST GSTM1; GSTT1; GSTM1 + GSTT1; GSTP1_105; GSTP1_114
Leoncini E, 2015 [41] Italy Cohort; 2001–2012 801 HNC 59 b) months [1.6–76] at HNC 62 a) 79.5 NR oral cavity (23.8); oropharynx (17.4); hypopharynx (5.4); larynx (49.7) I (25.6);
II (22.1);
III (18.8);
IV (33.5)
117 (14.6) head and neck, lung 4 ADH1B; ADH7 ADH1B rs1229984;
ADH7 rs1573496
Jefferies S, 2005 [42] England Case control; NR 61 HNC SPC cases; 259 controls NR at HNC 58.9 a); at SPC 64.4 a) 37Male SPC NR oral cavity (46); oropharynx (13); hypopharynx (8); larynx (33) NR 61 (100) HNC; prostate; ovary, breast, lung, colon; stomach; bladder; blood, melanoma 3 GPX1 GPX1 Polymorphisms: GPX1 ALA5; GPX1 ALA6; GPX1 ALA7
Lei D, 2010 [43] USA, Texas Cohort; 1995–2007 1.282 HNC 2.84b) [0–11.8] at HNC 57.4a);
at SPC 60.8 a)
at HNC 76.1;
at SPC: 23.9
Non-Hispanic white (84.5) oral cavity (32.4); oropharynx (44.7); hypopharynx/larynx (22.9) I or II (25.2);
III or IV (74.8)
120 (9.4) any SPC 6 p21 p21 C98A (rs1801270); p21 C70T (rs1059234)
Lei D, 2010 [25] USA, Texas Cohort; 1995–2007 1.286 HNC 2.47b) [0–11.8] at HNC 57.5a);
at SPC 60.8 a)
at HNC 76.0; at SPC 24.0 Non-Hispanic white (84.5) oral cavity (32.4); oropharynx (44.6); hypopharynx/larynx (23.0) I or II (25.2);
III or IV (74.8)
120 (9.3) any SPC 10;
1
FAS;
FASL
FAS − 1377 (G > A) (rs2234767); FAS -670A > G (rs1800682); FASLG -844C > T (rs763110); FASLG -124A > G (rs5030772)
Guan X, 2013 [26] USA, Texas Case control; 1999–2007 1.066 HNC SPC cases; 1.074 controls NR Cases 57.1a) (11.2);
Controls 56.7 a) (11.0)
Cases: 75.3
Controls: 76.3
Non-Hispanic White (100) oropharynx (50.7);
non-oropharynx (49.3)
NR 49 (5.8) NR 4 CASP3 rs1049253 T > C
Zhang Y, 2012 [27] USA, Texas Cohort; 1995–2007 1.269 HNC 2.17b) [0–11.8] 57 b) 75.6 Non-Hispanic white (85.4) oral cavity (31.9); oropharynx (45.2); hypopharynx/larynx (22.9) I or II (25.9);
III or IV (74.1)
109 (8.6) NR 4 p53; p73 p53 codon 72; p73 G4C14-to-A4T14
Gal TJ, 2005 [28] USA,Washington Cohort; 1988–1995 279 HNC NR at HNC 54a) (8.6) 71.3 Caucasian (92.8) oralcavity (100) NR 85 (30.5) lung and trachea, larynx, oral cavity, oropharynx, esophagus 19;
14;
10
XRCC1; XRCC3; XPD; MGMT XRCC1 Arg 399 Gln; XRCC3 Thr 241 Met; XPD Lys 751 Gln; MGMT Leu84Phe; MGMT Val143Ile
Sun Y, 2016 [29] USA, Texas Cohort; 1995–2010 1.529 HNC 4.27b) at OPC 54 b) [28–84];
at non-OPC: 59 b) [18–94]
77.5 Non- Hispanic white (87.2) oropharynx (49.2);
non-oropharynx (50.8)
I or II (25.2);
III or IV (74.8)
42 OPC (5.6);
82 non-OPC (10.9)
NR 10;
1
FAS;
FASL
rs1800682; rs2234767; rs5030772; rs763110
Wang Z, 2012 [30] USA, Texas Cohort; 1995–2007 1.292 HNC 2.8b) [0–11.8] at HNC 57.4 a) 76 Non-Hispanic white (84.6) oral cavity (32.5); oropharynx (44.5); larynx/hypopharynx (23.0) I or II (25.3);
III or IV (74.7)
120 (9.3) 81 tobacco related; 35 non-tobacco related; 4 both tobacco and non-tobacco related 12;
6
CDKN1B;
P21
rs2066827; rs1801270; rs1059234
Zhang Y, 2011 [31] USA, Texas Cohort; 1995–2007 1.287 HNC 2.47b) [0–11.8] at HNC 57b) [18–94] 75.9 Non-Hispanic white (84.6) oral cavity (32.3); oropharynx (44.6); larynx/hypopharynx (23.1) I or II (25.2);
III or IV (74.8)
120 (9.3) HNC, lung, esophagus, bladder, blood, prostate, colon, thyroid, breast, kidney, liver, endometrium, maxillary sinus 9 p14ARF rs3731217; rs3088440
Jin L, 2013 [32] USA, Texas Cohort; 1995–2007 1.283 HNC 2.83b) [0.2–11.8] at HNC 57 b) 76.0 Non-Hispanic white (84.6) oral cavity (32.4); oropharynx (44.6); larynx/hypopharynx (23.0) I or II: (25.2);
III or IV: (74.8)
120 (9.3) tobacco related: esophagus, lung, bladder; non- tobacco related: prostate, thyroid, colon 17;
1;
9;
12;
p53;
p73;
p14ARF; MDM2;
MDM4
p53 codon 72 (rs1042522);
rs2273953; rs3731217;
rs3088440; rs2279744;
rs937283; rs11801299;
rs1380576; rs10900598
Azad AK, 2012 [33] Canada Cohort;1994–2000 531 HNC 5.12b) 63 b) [33–86] 79 NR oralcavity (12); pharynx (5); larynx (83) Stage I (62.0);
Stage II (38.0)
111 (21) lung, head and neck, prostate, skin, colorectum kidney, breast, esophagus, bladder, blood, hypothalamus. 1; 2; 5; 9; 11; 13; 14; 16; 17; 19; 22; CCND1; TP53; DNMT3B; ERCC1; ERCC2; ERCC4; ERCC5; MSH2; XPA; XRCC1; XRCC3; FGFR4; CTLA4; MMP3; CYP2D6 rs603965; rs678653;
rs1042522; rs2424913;
rs3212986; rs1799793; rs13181; rs1799801;
rs1047768; rs17655;
rs2303426; rs1800975;
rs25487; rs861539;
rs351855; rs231775;
rs35068180; rs35742686;
rs3892097
Wu X, 2009 [36] USA, Texas Nestle Case-control; 1991–1999 150 HNC SPC cases; 300 controls NR Cases 61.40 a) (10.2); Controls 61.05 a) (10.18) 80 Caucasian (99.7) larynx (47);
oral (32);
pharynx (21)
I (59.0);
II (41.0)
150 (100) NR 10; 2; 7 MKI67; NHEJ1; CDK6;TNFRSF10B; MNAT1; GSTM4; GLI2; RNF2; CAT; PROM1; IGF1R; CFTR; AXIN1; CHFR; GSTM4; KRAS; MRC2; BRCA2; PDGFB rs12359892; rs359974;
rs7781436; rs876435;
rs12888332; rs506008;
rs7561607; rs6684195;
rs17387169; rs7168671;
rs7591; rs2306536; rs7118388; rs9622978;
rs2237724; rs604337;
rs3826537; rs9562605;
rs2300181; rs11047917
Minard CG, 2006 [34] USA, Texas Cohort;1991–2006 303 HNC 4a) at HNC 62.5 a) (10.6) 83.8 Caucasian (100) larynx (65.7); oral (23.8); pharynx (10.6) I (67.0);
II (33.0)
50 (16.5) head and neck pharynx, larynx, lung, esophagus, bladder, kidney, pancreas, prostate 1;
22
GST-M1;
GST-T1
GST-M1 null genotype;
GST-T1 null genotype
Zhang X, 2010 [38] USA, Texas nested case–control; 1991–1999 150 HNC SPC cases; 300 controls NR Cases 61.4 a) (10.21); Controls 61.05 a) (10.18) 80 Caucasian (99.7) larynx (58.4); oral (28.8); pharynx (12.7) I (63.5);
II (36.5)
150 (100) NR 22 SMC1B; BCL2L2; GSTM3; IL1R1; NR1I2; SSTR2; SUFU; RAN; XPO5; RNASEN rs3747238; rs1884056; rs15864; rs3917328; rs3732360; rs7210080; rs11594179; rs11061209; rs2227301; rs699937; rs7735863; rs6884823;
rs3792830; rs669702;
rs639174; rs3805500;
rs7719666; rs17410035
  1. Abbreviations: NR not reported, HNC head and neck cancer, SPC Second primary cancer; SD standard deviation; IQR interquartile range; OPC oropharyngeal cancer; SNP Single nucleotide polymorphisms