Meta- and Pooled Analyses of GSTM1, GSTT1, GSTP1, and CYP1A1 Genotypes and Risk of Head and Neck Cancer

Mia Hashibe; Paul Brennan; Richard C. Strange; Rajani Bhisey; Ingolf Cascorbi; Philip Lazarus; Michael B. Oude Ophuis; Simone Benhamou; William D. Foulkes; Takahiko Katoh; Christiane Coutelle; Marjorie Romkes; Laura Gaspari; Emanuela Taioli; Paolo Boffetta

DOI: Published December 2003

Article Figures & Data

Tables

Table 1

Summary of case–control studies on GSTM1, GSTT1, GSTP1 (ILE105VAL), and CYP1A1 (ILE462VAL) genotypes and head and neck cancers

Ref.	First author	Year of publication	Country	Control source	Matching	Site
Ref.	First author	Year of publication	Country	Control source	Matching				Oral	Pharynx	Larynx
(13)	Buch	2002	India	Hospital-healthy	Individual	X
(14)	Cheng	1999	United States	Hospital	Individual	Head & neck; site NS
(15)	Coutelle	1997	France	Alcoholism clinic	None		X	X
(16)	Deakin	1996	United Kingdom	Hospital	None	X
(17)	Gonzalez	1998	Spain	Hospital-healthy	None	X	X	X
(18)	Gronau	2003	Germany	Hospital-healthy	Individual	X	X	X
(19)	Hahn	2002	Germany	Hospital-healthy	Individual	X
(20)	Hamel	2000	Canada	Mixed	Individual	X	X	X
(21)	Hanna	2001	United States	Hospital	Individual			X
(22)	Hong	2000	Korea	Hospital	None			X
(23)	Hung	1997	Taiwan	Population based	Frequency	X
(24)	Jaskula-Sztul	1998	Poland	NS, healthy	None			X
(25 , 26)	Jourenkova	1999	France	Hospital	Frequency	X	X	X
(26 , 27)	Jourenkova	1999	France	Hospital	Frequency	X	X	X
(28)	Kao	2002	Taiwan	Hospital	None	X
(29)	Katoh	1999	Japan	Hospital-healthy	None	X
(30)	Katoh	1999	Japan	Hospital-healthy	None	X
(31)	Kietthubthew	2001	Thailand	Population based	Individual	X
(32)	Kihara	1997	Japan	Hospital-healthy	None	X	X	X
(33)	Ko	2001	Germany	Hospital-healthy	None	Head & neck; site NS
(34)	Matthias	1998	Germany	Hospital	None	X	X	X
(35)	Matthias	1999	Germany	Hospital	None	X	X	X
(36)	McWilliams	2000	United States	Hospital	None	X	X	X
(37)	Morita	1999	Japan	Hospital-healthy	None	X	X	X
(38)	Nomura	2000	Japan	Hospital	None	X	X
(39)	Olshan	2000	United States	Hospital	Frequency	X	X	X
(40)	Oude Ophuis	1998	Netherlands	Hospital-healthy	None	X	X	X
(41)	Oude Ophuis	2003	Netherlands	Hospital-healthy	None	X	X	X
(42)	Park	1997	United States	Hospital	Frequency	X	X	X
(43)	Park	1999	United States	Hospital	Frequency	X	X	X
(44)	Park	2000	United States	Hospital	Frequency	X	X	X
(45)	Risch	2003	Germany	Population based	Frequency			X
(46)	Sato	2000	Japan	Hospital-healthy	None	X
(47)	Sreelekha	2001	India	Hospital-healthy	Individual	X
(48)	Tanimoto	1999	Japan	Hospital	Individual	X
(49)	To-Figueras	2002	Spain	Hospital-healthy	None			X
(50)	Trizna	1995	United States	Hospital-healthy	None	X	X	X
No. of studies in meta-analysis
Cases
Controls
Summary OR (95% CI)
Test for heterogeneity
Publication bias (Egger’s test)

Table 1A

Continued

Cases (n)	Controls (n)	GSTM1 null, crude OR^a (95% CI)	GSTT1 null, crude OR (95% CI)	GSTP1 (any Val), crude OR (95% CI)	CYP1A1 (any Val), crude OR (95% CI)
297^b,^c	450^c	2.95 (2.16–4.04)^d	1.60 (1.06–2.41)^d
162	315	1.51 (1.03–2.21)	2.30 (1.48–3.56)
39^c,^e,^f	37^c,^e,^f	2.38 (0.93–6.06)^d,^g
40ⁱ	577ⁱ	1.01 (0.53–1.92)^d	0.59 (0.20–1.71)^d
75^f	200^f	1.34 (0.78–2.29)^d
187	139	0.78 (0.50–1.21)^d	1.07 (0.59–1.97)^d		1.30 (0.70–2.41)^d
94	92	1.29 (0.72–2.31)^d			0.64 (0.17–2.34)^d
90^b,^h	90	0.96 (0.53–1.73)^d	2.57 (1.12–5.90)
20	20	4.00 (0.98–16.27)^d,^g	0.71 (0.14–3.66)^d
82^c,^f	63^c,^f	1.96 (0.99–3.86)^d	2.34 (1.19–4.58)^d
41^f	123^f	1.03 (0.50–2.12)^d	1.26 (0.61–2.58)^d
171	180	0.71 (0.46–1.08)	0.77 (0.45–1.31)
250^c	172^c	1.09 (0.74–1.60)^d	1.38 (0.82–2.30)^d
250^c	172^c			1.23 (0.86–1.82)^d
106	146				5.42 (2.83–10.38)^d,^g
92	147	1.65 (0.98–2.80)	0.88 (0.52–1.48)		1.29 (0.76–2.18)
83	122			1.91 (1.04–3.52)^d
53	53	3.02 (1.36–6.71)^d	0.58 (0.26–1.26)
156^h	472	1.29 (0.90–1.86)^d
312	300	1.22 (0.88–1.67)^d	1.01 (0.68–1.50)^d
380	193				1.04 (0.64–1.70)^d
398^h	219^h	1.18 (0.82–1.68)^d	0.99 (0.66–1.49)^d	1.39 (0.98–1.96)^d
160^h,ⁱ	149ⁱ	0.99 (0.62–1.59)	0.91 (0.47–1.74)	1.26 (0.78–2.04)^d	0.42 (0.18–0.99)
145	164	0.94 (0.60–1.46)^d		0.73 (0.44–1.21)^d	0.88 (0.55–1.41)^d
109^h	33	2.43 (1.10–5.38)^d,^g
182ⁱ	202ⁱ	0.96 (0.64–1.46)^d,^g	1.47 (0.84–2.58)^d	1.25 (0.81–1.92)^d	1.33 (0.58–3.06)^d
185^b,^h	207	0.97 (0.65–1.44)^d	0.95 (0.58–1.56)^d		1.15 (0.68–1.93)^d
235ⁱ,^j	285			0.80 (0.57–1.13)^d
131	131				2.58 (1.17–5.66)^d
154	246			0.91 (0.60–1.38)^d
164	344	1.34 (0.92–1.95)^d
245	251	0.92 (0.65–1.32)^d	1.13 (0.69–1.86)^d
142	142	2.24 (1.40–3.61)			1.88 (1.17–3.03)^d
98	60	1.92 (0.99–3.74)^d	2.48 (0.87–7.06)^d		5.21 (2.37–11.43)^d
100	100	1.04 (0.59–1.83)^d
204ⁱ	203^c,ⁱ	0.92 (0.62–1.35)^d	0.67 (0.41–1.09)^d	1.01 (0.68–1.49)^d
186ⁱ	42ⁱ	2.37 (1.20–4.67)	1.47 (0.71–3.02)

		26	21	9	11
		4224	3346	1768	1764
		5333	3829	1699	1585
		1.23 (1.06–1.42)	1.17 (0.98–1.40)	1.10 (0.92–1.31)	1.32 (0.95–1.82)
		0.00	0.01	0.13	0.00
		0.99	0.97	0.52	0.89

^a OR, odds ratio; CI, confidence interval; NS, not specified.
^b Prevalent and incident cases.
^c All ever tobacco smokers and/or chewers.
^d Odds ratio calculated.
^e All drinkers.
^f All males.
^g Study excluded.
^h Includes nasopharyngeal, maxillary sinus, and/or salivary gland cancers.
ⁱ Number of cases and controls genotyped varied for each gene, thus overall numbers are presented.

Table 2

Distribution of GSTM1, GSTT1, GSTP1 (ILE105VAL), and CYP1A1 (ILE462VAL) genotypes among head and neck cancer cases and controls

Ref.	Country	% GSTM1 null			% GSTT1 null			% GSTP1 any Val			% CYP1A1 any Val
Ref.	Country			Cases	Controls	Cases	Controls	Cases	Controls	Cases	Controls
Asia
(13)	India	49.2	24.7	18.2	12.2
(47)	India	49.0	33.3	18.4	8.3			51.0	16.7
(29 , 30)	Japan	58.7	46.3	47.8	51.0	37.3	23.8^a	45.7	39.5
(32)	Japan	55.1	48.7
(37)	Japan	49.0	50.6			24.8	31.1	33.8	36.6
(38)	Japan	67.0	45.5
(46)	Japan	64.8	45.1					52.1	36.6
(48)	Japan	43.0	42.0
(22)	Korea	68.3	52.4	57.3	36.5
(23)	Taiwan	58.5	57.7	58.5	52.8
(28)	Taiwan							86.8	54.8^a
(31)	Thailand	56.6	30.2	34.0	47.2
Overall in Asia		55.0	41.7	30.9	27.7	29.3	28.0	52.7	39.5
Europe
(15)	France	69.2	48.6
(25 26 27)	France	54.4	52.3	20.4	15.7	55.2	50.0
(18)	Germany	42.8	48.9	16.0	15.1			17.1	13.7
(19)	Germany	59.6	53.3					4.3	6.7
(33)	Germany	53.2	48.3	20.5	20.3
(34 , 35)	Germany	57.4	53.4	22.0	22.2	55.0	46.9^a	15.0	14.5
(45)	Germany	51.8	53.8	15.5	13.9
(40 , 41)	Netherlands	50.8	51.7	19.5	20.3	50.6	56.1	18.4	16.4^a
(24)	Poland	49.1	57.8	17.5	21.7
(17)	Spain	58.7	51.5
(49)	Spain	47.1	49.3	17.2	23.6	50.7	50.2
(16)	United Kingdom	55.0	54.8	11.8	18.5
Overall in Europe		52.7	52.4	19.3	19.6	53.3	51.4	15.0	13.8
North America
(20)	Canada	56.7	57.8	22.2	10.0
(14)	United States	53.1	42.9	32.7	17.5
(21)	United States	80.0	50.0	15.0	20.0
(36)	United States	46.3	46.5	16.9	18.3	58.9	53.2	6.5	14.0
(39)	United States	43.6	44.6	18.6	13.5	66.3	61.1	7.6	5.8
(42 43 44)	United States	43.3	36.3			62.3	64.6	17.6	7.6^a
(50)	United States	68.3	47.6	44.9	35.7
Overall in North America		52.5	43.1	26.5	16.8	62.7	60.9	9.4	7.8
Overall		53.3	47.0	22.9	20.6	52.7	50.6	23.9	21.1

^a Departure from Hardy–Weinberg equilibrium detected (P < 0.05). Hardy–Weinberg equilibrium was assessed among the controls for GSTP1 and CYP1A1.

Table 3

Meta-analysis of case–control studies for GSTM1, GSTT1, and head and neck cancer

	GSTM1							GSTT1
		No. of studies	OR^a for null genotype (95% CI)	Test for heterogeneity	Egger’s test	No. of studies	OR^a for null genotype (95% CI)	Test for heterogeneity	Egger’s test
Overall	30	1.30 (1.12–1.50)	0.00	0.02	21	1.17 (0.98–1.40)	0.01	0.97
Excluding studies	26^b	1.23 (1.06–1.42)	0.00	0.99
Cancer site
Oral	10^c	1.45 (1.05–2.00)	0.00	0.31	7^d	1.15 (0.82–1.63)	0.10	0.44
Larynx	9^e	1.10 (0.86–1.41)	0.02	0.65	7^f	1.00 (0.74–1.36)	0.09	0.77
Smoking status
Never smokers	4^g	0.98 (0.58–1.65)	0.85	0.78
Ever smokers^h	8ⁱ	1.37 (0.97–1.94)	0.00	0.59	5^j	1.24 (0.92–1.66)	0.24	0.90
Region
Asia	9	1.58 (1.16–2.14)	0.00	0.29	6	1.31 (0.88–1.96)	0.04	0.99
North America	6	1.24 (0.98–1.57)	0.17	0.76	6	1.59 (1.12–2.26)	0.17	0.34
Europe	11	1.02 (0.90–1.15)	0.57	0.91	9	0.96 (0.81–1.14)	0.63	0.43
Year of publication
1995–1999	14	1.22 (1.03–1.43)	0.04	0.45	9	1.14 (0.87–1.48)	0.04	0.50
2000–2003	12	1.24 (0.96–1.59)	0.00	0.65	12	1.20 (0.93–1.55)	0.02	0.69
No. of cases and controls
<100 cases or <100 controls	9	1.42 (1.16–1.74)	0.45	0.69	9	1.26 (0.86–1.85)	0.04	0.02
≥100 cases & 100≥controls	17	1.16 (0.97–1.39)	0.00	0.16	12	1.14 (0.93–1.39)	0.02	0.47
Control source
Hospital-healthy or population	16	1.27 (1.02–1.59)	0.00	0.02	12	1.03 (0.85–1.25)	0.17	0.77
Hospital	10	1.17 (1.02–1.34)	0.66	0.96	9	1.41 (1.04–1.93)	0.03	0.64
Matching
Individual matching	7	1.38 (0.92–2.08)	0.00	0.16	7	1.50 (1.01–2.22)	0.03	0.50
Frequency matching	5	1.07 (0.89–1.27)	0.69	0.93	4	1.30 (0.98–1.71)	0.91	0.83
No matching	14	1.21 (1.02–1.43)	0.02	0.15	10	0.97 (0.79–1.18)	0.22	0.70

^a OR, odds ratio (adjusted for study center); CI, confidence interval.
^b Excluded (15 , 21 , 31 , 38) .
^c Included (13 , 16 , 19 , 23 , 25 , 26 , 29 , 31 , 37 , 38 , 46 47 48) .
^d Included (13 , 16 , 23 , 26 , 29 , 31 , 47) .
^e Included (15 , 18 , 21 , 22 , 22 , 24 25 26 , 32 , 35 , 37 , 45 , 49) .
^f Included (21 , 22 , 24 , 25 , 35 , 45 , 49) .
^g Included (32 , 39 , 43 , 45) .
^h Ever smoking was categorized by different criteria in the studies: smoked for at least 5 years (23) ; smoked at least 5 cigarettes/day for 4 years (33) ; smoked at least 5 cigarettes/day for 5 years (25 26 27) ; smoked at least 100 cigarettes in a lifetime (39) ; smoked >0 pack-years (44 , 45) ; and not specifically defined (30 , 32) .
ⁱ Included (13 , 15 , 22 , 25 , 26 , 32 , 33 , 39 , 43 , 45) .
^j Included (22 , 25 , 26 , 33 , 39 , 45) .

Table 4

Meta-analysis of case–control studies for GSTP1 (ILE105VAL), CYP1A1 (ILE462VAL), and head and neck cancer

	GSTP1							CYP1A1
		No. of studies	OR^a for any Val (95% CI)	Test for heterogeneity	Egger’s test	No. of studies	OR^a for any Val (95% CI)	Test for heterogeneity	Egger’s test
Overall	9	1.10 (0.92–1.31)	0.13	0.52	12	1.48 (1.01–2.16)	0.00	0.76
Excluding studies					11^b	1.32 (0.95–1.82)	0.00	0.89
Cancer site
Oral	3^c	1.52 (1.05–2.20)	0.63	0.22	5^d	1.48 (0.77–2.83)	0.00	0.80
Larynx	5^e	0.94 (0.73–1.20)	0.20	0.42	3^f	1.03 (0.65–1.62)	0.29	0.07
Smoking status
Never smokers
Ever smokers^g	3^h	1.15 (0.87–1.51)	0.49	0.86
Region
Asia					4	1.73 (0.93–3.23)	0.00	0.18
North America	3	1.11 (0.86–1.43)	0.48	0.56	3	1.14 (0.41–3.21)	0.01	0.26
Europe	4	1.08 (0.85–1.38)	0.14	0.94	4	1.10 (0.82–1.49)	0.79	0.35
Year of publication
1995–1999	5	1.15 (0.87–1.53)	0.08	0.97	5	1.18 (0.89–1.57)	0.23	0.01
2000–2003	4	1.02 (0.82–1.27)	0.33	0.07	6	1.37 (0.73–2.56)	0.00	0.48
No. of cases and controls
<100 cases or <100 controls					3	1.74 (0.57–5.28)	0.00	0.99
≥100 cases & 100≥controls	8	1.06 (0.90–1.24)	0.24	0.68	8	1.20 (0.88–1.63)	0.04	0.88
Control source
Hospital-healthy or population	4	0.98 (0.70–1.17)	0.07	0.36	7	1.43 (0.96–2.12)	0.01	0.74
Hospital	5	1.21 (1.01–1.45)	0.65	0.56	4	1.12 (0.58–2.13)	0.02	0.99
Matching
Individual/frequency matching	3	1.12 (0.89–1.42)	0.47	0.60	5	1.84 (0.98–3.46)	0.02	0.72
No matching	4	1.18 (0.90–1.55)	0.12	0.90	6	1.09 (0.79–1.50)	0.05	0.14

^a OR, odds ratio (adjusted for study center); CI, confidence interval.
^b Excluded (28) .
^c Included (26 , 30 , 37) .
^d Included (19 , 29 , 37 , 46 , 47) .
^e Included (27 , 35 , 37 , 41 , 49) .
^f Included (34 , 37 , 43) .
^g Ever smoking was categorized by different criteria in the studies: smoked at least 5 cigarettes/day for 5 years (26 , 27) , smoked at least 100 cigarettes in a lifetime (39) , and not specifically defined (30) .
^h Included (26 , 27 , 30 , 39) .

Table 5

Pooled analysis of case–control studies on the GSTM1, GSTT1, GSTP1 (ILE105VAL), and CYP1A1 (ILE462VAL) genotypes and head and neck cancer

Principal investigator	First author (Refs.)	Country	Control source	Site					Cases (n)	Controls (n)	GSTM1 (null), OR^a (95% CI)	GSTT1 (null), OR (95% CI)	GSTP1 (any Val), OR (95% CI)	CYP1A1 (any Val), OR (95% CI)
Principal investigator	First author (Refs.)	Country	Control source					Oral	Cases (n)	Controls (n)	GSTM1 (null), OR^a (95% CI)	GSTT1 (null), OR (95% CI)	GSTP1 (any Val), OR (95% CI)	CYP1A1 (any Val), OR (95% CI)	Pharynx	Larynx
Benhamou	Jourenkova (25 26 27)	France	Hospital	X	X	X	250	172	1.09 (0.74–1.60)	1.38 (0.82–2.30)	1.23 (0.83–1.82)
Bhisey	Buch (13)	India	Hospital- healthy	X			300^b^c^d	678^c,^d	1.73 (1.49–1.99)	1.61 (1.11–2.33)		1.06 (0.76–1.48)
Cascorbi	Unpublished	Germany	Hospital- healthy		X	X	505^f	223^f	2.01 (1.34–3.01)	1.26 (0.65–2.43)		1.02 (0.51–2.04)
Coutelle	Coutelle (15)	France	Alcoholism clinic		X	X	39^c,^d,^e	76^c,^d,^e	2.37 (1.05–5.36)
Foulkes	Hamel (20)	Canada	Mixed	X	X	X	196^b,^f	199^f	1.09 (0.74–1.62)	1.15 (0.67–1.98)
Katoh	Katoh (29 , 30)	Japan	Healthy	X			45	91	1.59 (0.78–3.27)
Lazarus	Park (42 43 44)	United States	Hospital	X		X	185^f	367^f	1.40 (0.96–2.03)		0.87 (0.57–1.33)
Manni	Oude Ophuis (40)	Netherlands	Hospital- healthy	X	X	X	245^b,^f	159^f	1.33 (0.77–2.29)	0.56 (0.30–1.05)	0.77 (0.52–1.14)	0.63 (0.33–1.19)
Romkes	Unpublished	United States	Healthy	Head and neck					40^f	70^f	0.79 (0.36–1.73)	0.84 (0.25–2.84)
Strange	Deakin (16)	United Kingdom	Hospital	X			107^f	493^f	0.69 (0.45–1.05)	1.38 (0.84–2.27)	1.53 (0.94–2.48)	2.11 (0.85–5.24)
Strange	Matthias (34 , 35)	Germany	Hospital	X	X	X	422^f	238^f	1.31 (0.94–1.83)	1.54 (0.91–2.63)	1.56 (1.11–2.19)	0.87 (0.55–1.38)
No. of studies (cases/controls) in data									11 (2224/2517)	8 (1929/1830)	5 (1164/982)	5 (1558/1467)
Summary OR^a									1.32 (1.07–1.62)	1.25 (1.00–1.57)	1.15 (0.86–1.53)	0.98 (0.75–1.29)
Test for heterogeneity									0.00	0.22	0.04	0.28
Publication bias (Egger’s test)									0.15	0.14	0.75	0.79
Oral									1.20 (0.89–1.63)	1.34 (0.99–1.82)	1.37 (0.88–2.14)	0.97 (0.56–1.69)
Pharynx									1.25 (0.98–1.61)	1.11 (0.66–1.87)	1.10 (0.58–2.05)	0.77 (0.47–1.25)
Larynx									1.53 (1.17–2.00)	1.10 (0.81–1.49)	1.08 (0.81–1.44)	0.93 (0.64–1.34)
Never smokers									1.58 (1.11–2.23)	1.29 (0.83–1.99)	1.38 (0.46–4.12)	0.95 (0.62–1.45)
Ever smokers									1.33 (1.01–1.74)	1.23 (0.77–1.94)	1.01 (0.76–1.33)	0.87 (0.50–1.51)
Caucasians									1.19 (0.93–1.51)	1.17 (0.91–1.50)	1.15 (0.86–1.54)	0.95 (0.64–1.43)
SCC									1.24 (0.99–1.54)	1.17 (0.88–1.55)	1.13 (0.83–1.54)

^a OR, odds ratio (all ORs from the pooled analysis are adjusted for study center); CI, confidence interval; SCC, squamous cell carcinoma.
^b Prevalent and incident cases.
^c All ever tobacco smokers and/or chewers.
^d All males.
^e All drinkers.
^f Number of cases and controls genotyped varied for each gene; thus, overall numbers are presented.