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

Li F, 2010 [23]

USA, Texas

Cohort;1995–2007

1.271 HNC

2.2^b) [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 2.3^b;

controls 5.0^b

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

2.2^b) [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

2.2^b)

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

2.2^b)

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 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

2.84^b) [0–11.8]

at HNC 57.4^a);

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

2.47^b) [0–11.8]

at HNC 57.5^a);

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 57.1^a) (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

2.17^b) [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 54^a) (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

4.27^b)

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

2.8^b) [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

2.47^b) [0–11.8]

at HNC 57^b) [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

2.83^b) [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

5.12^b)

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

4^a)

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