Environmental tobacco smoke exposure and lung cancer: A systematic review

Table 1 Selected details of the 102 studies in publication date order

Study ref	Main ref	Other ref	Location	Study design1	Study dates2			Total cases	Never smoker criteria3
GARFI1	[75]	[104]	United States	P	1959 -	1960,	1971	153	Dur 6 mo
CHAN	[105]	[106,107]	Hong Kong	CC	1976 -	1977		84
CORREA	[67]		United States	CC	1979 -	1982		32
TRICHO	[27]	[108,109]	Greece	CC	1978 -	1982		77
BUFFLE	[110]		United States	CC	1976 -	1980		52
HIRAYA	[28]	[111-120]	Japan	P	1965 -	1966,	1981	264
KABAT1	[53]		United States	CC	1971 -	1980		76
GARFI2	[121]	[122]	United States	CC	1971 -	1981		134
LAMW	[29]		Hong Kong	CC	1981 -	1984		75
WU	[123]		United States	CC	1981 -	1982		31
AKIBA	[68]		Japan	CC	1971 -	1980		113
LEE	[124]		United Kingdom	CC	1979 -	1982		47
BROWN1	[125]		United States	CC	1979 -	1982		19
GAO	[126]		China	CC	1984 -	1986		246
HUMBL1	[127]		United States	CC	1980 -	1984		28	Dur 6 mo
KOO	[128]	[129-133]	Hong Kong	CC	1981 -	1983		88	N20
LAMT	[30]		Hong Kong	CC	1983 -	1986		199	Occ (1 yr)
PERSHA	[134]	[135]	Sweden	CC	1961 -	1980		77
BUTLER	[136]		United States	P	1976 -	1976,	1982	8
GENG	[31]	[137]	China	CC	1983 -	1983		54
INOUE	[138]		Japan	CC	1973 -	1983		28
SHIMIZ	[70]		Japan	CC	1982 -	1985		90
CHOI	[139]		South Korea	CC	1985 -	1988		88
HOLE	[140]	[141]	Scotland	P	1972 -	1976,	1985	9
SCHOEN	[142]		United States	CC	1982 -	1983		116
SVENSS	[143]	[144]	Sweden	CC	1983 -	1985		34	Occ
JANERI	[72]	[145]	United States	CC	1982 -	1985		191	N100
KALAND	[32]		Greece	CC	1987 -	1989		91
SOBUE	[146]	[147]	Japan	CC	1986 -	1988		144
WU-WIL	[46]		China	CC	1985 -	1987		417
LIUZ	[148]	[149,150]	China	CC	1985 -	1986		54	1sm
BROWN2	[151]	[152-155]	United States	CC	1986 -	1991		432
STOCKW	[58]	[156]	United States	CC	1987 -	1991		210	N100, Dur 6 mo
DU	[52]	[157-159]	China	CC	1986 -	1986		75
LIUQ	[160]		China	CC	1983 -	1984		38
FONTHA	[33]	[161-164]	United States	CC	1986 -	1988		653	N100, Dur 6 mo
LAYARD	[165]		United States	CC	1986 -	1986		60
DEWAAR	[166]	[167]	Netherlands	CC	1977 -	1991		23	Cot
KABAT2	[168]	[169,170]	United States	CC	1983 -	1990		110
SCHWAR	[57]		United States	CC	1984 -	1987		257
SUN	[60]		China	CC	NA			230
WANGS	[34]		China	CC	NA			82
WANGT	[171]		China	CC	1992 -	1994		135
CARDEN	[73]	[172,173]	United States	P	1982 -	1982,	1989	362
ZHENG	[35]		China	CC	1990 -	1993		94	Non
AUVINE	[174]		Finland	CC	1986 -	1992		44
BOFFET	[66]	[175-180]	West Europe	CC	1988 -	1994		640	N400
SHEN	[181]	[182-185]	China	CC	1993 -	1993		70
ZARIDZ	[36]	[186-188]	Russia	CC	1991 -	1993		189
BOFFE2	[189]		Europe	CC	1994 -	1996		70	N400
JEE	[190]		South Korea	P	1992 -	1994,	1997	79	Occ, Dur 1 yr
RAPITI	[61]		India	CC	1991 -	1992		58	N400
SPEIZE	[191]		United States	P	1982 -	1982,	1992	35
ZHONG	[54]		China	CC	1992 -	1994		504	Dur 6 mo
LEECH	[37]	[192-194]	Taiwan	CC	1992 -	1998		268	N400
MALATS	[195]	[196]	Europe/Brazil	CC	NA			122	Occ
WANGL	[62]	[197]	China	CC	1994 -	1998		233	Dur 6 mo
JOHNSO	[198]	[199-201]	Canada	CC	1994 -	1997		71	N100
LAGARD	[202]	[203]	Sweden	CC	1980 -	1995		433	Occ (1 yr)
NISHIN	[204]		Japan	P	1984 -	1984,	1992	24
OHNO	[205]		Japan	CC	NA			191	N365
RACHTA	[63]	[206]	Poland	CC	1991 -	1997		54	Dur 6 mo
ENSTRO	[207]	[208]	United States	P	1959 -	1960,	1998	256
ZATLOU	[64]	[209,210]	Czech Republic	CC	1998 -	2002		84	N100
IARCKR	[1]	[180]	Germany	CC	1990 -	1996		123	Dur 6 mo, N400
MCGHEE	[211]		Hong Kong	CC	1998 -	1998		324
EPICA	[212]	[213-216]	Western Europe	P	1993 -	1998,	2000	59
FANG	[38]	[216]	China	CC	2001 -	2004		157
FRANCO	[71]	[216]	Mexico	CC	2000 -	2002		94
GORLOV	[55]	[217-222]	United States	CC	1995 -	2003		193	N100
NEUBER	[49]		United States	CC	1994 -	1997		56	N100, Dur 6 mo
RYLAND	[223]		Sweden	CC	1989 -	1994		49
WEN	[56]	[224-227]	China	P	1997 -	2000,	2004	106
YU	[228]	[228-230]	Hong Kong	CC	2002 -	2004		213	N400, Dur 1 yr
ZEKA	[59]		East Europe, United Kingdom	CC	1998 -	2002		223	N100
HILL1	[231]		New Zealand	P	1981 -	1981,	1984	147	Occ
HILL2	[231]		New Zealand	P	1996 -	1996,	1999	234	Occ
LOPEZC	[232]		Spain	CC	2000 -	2005		36	N100
ASOMAN	[233]		United States	CC	1992 -	NA		138	Occ (1 yr)
GALLEG	[51]		Mexico	CC	2003 -	2007		32
KURAHA	[234]		Japan	P	1990 -	1993,	2004	109
PANDEY	[50]		Nepal	CC	NA			268
YANG	[39]	[65,221,235,236]	United States	CC	1997 -	2008		297	N100
OLIVOM	[65]	[237]	United States	CC	NA			45	N100
TSE	[238]	[239]	China	CC	2004 -	2006		132	N400, Dur 1 yr
LIANG	[40]		China	CC	2004 -	2007		226
BRENNE	[47]		Canada	CC	1997 -	2002		156	N100
JIANG	[41]		China	CC	2009 -	2009		145
EPICC	[240]	[212]	Western Europe	P	1992 -	1998,	2006	98
KIYOHA	[241]		Japan	CC	1996 -	2008		153
HE	[242]	[243]	China	P	1976 -	1994,	2011	16	N100
LIM	[74]	[244-246]	China	CC	1996 -	2008		433	Occ (1 yr)
LIN	[42]		China	CC	2006 -	2010		226
FERREC	[247]		Chile	CC	2007 -	2010		59
ALZOUG	[48]	[248,249]	Canada	CC	1996 -	2000		44	N100
GELAC	[43]		Taiwan	CC	2002 -	2009		1540	Occ
MASJED	[44]	[250]	Iran	CC	2002 -	2005		81	Dur 6 mo
REN	[251]		China	CC	2002 -	2012		764
SEKI	[252]		Japan	CC	1997 -	2009		431
WHIOS	[253]	[254]	United States	P	1993 -	1998,	2009	200
ILCCO	[45]	[69]	International	CC	1984 -	2014		2504	N100
TORRES	[255]	[256]	Spain	CC	2011 -	2013		192	N100

¹Study design is coded as P: Prospective; CC: Case control;

²Study dates are given as Start year, End year, Final follow-up year (prospective studies only);

³Inclusion of “near equivalents” to never smokers, coded as Dur: Includes those who smoked up to a number of months (mo) or years (yr); N: Includes those who smoked up to a number of cigarettes in their lifetime; Occ: Includes occasional smokers; Occ (1 yr): Includes those who smoked occasionally for up to 1 year; Non: Described as “non-smokers” and assumed from context to mean never smokers; 1sm: Study included 1 smoker; Cot: Excluded self-reported never smokers with urinary cotinine > 100 ng/mg.

Table 2 Further details of the 102 studies

Ref.	ETS exposures1	Adjustment variables used2	Extent (%) of histological confirmation	Results by histological type	Dose-response results available3
GARFI1	s	7	NA		Yes
CHAN	s	0	80
CORREA	s c4	1	97		Yes
TRICHO	s	0	27	Yes	Yes
BUFFLE	h	0	100		Yes
HIRAYA	s	2	NA		Yes
KABAT1	s h w	4	100
GARFI2	s h w c o tot	4	100	Yes	Yes
LAMW	s tot	1	100	Yes
WU	s w c tot4	2	100	Yes
AKIBA	s c	6	53		Yes
LEE	s h w tr o tot	3	38	Yes
BROWN1	tot	3	100	Yes
GAO	s h c tot	2	43		Yes
HUMBL1	s	2	100		Yes
KOO	s h w c tot	5	97	Yes	Yes
LAMT	s	0	100	Yes	Yes
PERSHA	s c	2	83	Yes	Yes
BUTLER	s	2	100
GENG	s	0	85		Yes
INOUE	s	3	NA		Yes
SHIMIZ	s h w	3	100
CHOI	s	0	100		Yes
HOLE	h	2	NA		Yes
SCHOEN	s	6	100
SVENSS	h c tot	1	70
JANERI	s h w c o	3	100	Yes	Yes
KALAND	s h w	5	48	Yes	Yes
SOBUE	s h c	3	100
WU-WIL	s h w c	5	42
LIUZ	h	3	17
BROWN2	s h w c	2	76	Yes	Yes
STOCKW	s h w4 c o4 tot	3	100	Yes	Yes
DU	s	2	NA		Yes
LIUQ	s	3	32		Yes
FONTHA	s h w c o tot	10	100	Yes	Yes
LAYARD	s	3	NA		Yes
DEWAAR	tot	0	71		Yes
KABAT2	s h w c tr o tot	6	100		Yes
SCHWAR	h w	2	100
SUN	s h w c hw tot	2	100	Yes
WANGS	tot	0	100
WANGT	s w c	1	57		Yes
CARDEN	s h w o tot	8	NA		Yes
ZHENG	h	2	82	Yes	Yes
AUVINE	tot	1	NA
BOFFET	s h w c tr o tot	7	96	Yes	Yes
SHEN	tot	9	100	Yes	Yes
ZARIDZ	s h w c	2	100	Yes	Yes
BOFFE2	s w c tot	5	100	Yes	Yes
JEE	s	5	0		Yes
RAPITI	s w c tr	3	100	Yes	Yes
SPEIZE	tot	1	100
ZHONG	s h w c tot	7	57	Yes	Yes
LEECH	s h w c tot	7	100		Yes
MALATS	s tot	2	100		Yes
WANGL	h c	6	32		Yes
JOHNSO	h w c tot	4	100		Yes
LAGARD	h tot	6	100
NISHIN	s h	7	NA
OHNO	s w c tr o tot	2	100		Yes
RACHTA	c	21	100	Yes
ENSTRO	s	8	NA
ZATLOU	c tot	3	100	Yes
IARCKR	s w c	2	100		Yes
MCGHEE	h	2	0		Yes
EPICA	h w tot	7	NA
FANG	tot	8	100		Yes
FRANCO	h	2	100
GORLOV	h w hw tot	4	100
NEUBER	tot4	3	100
RYLAND	h w	3	98
WEN	s w c tot	9	NA		Yes
YU	tot	20	100		Yes
ZEKA	w	4	NA		Yes
HILL1	h	9	NA
HILL2	h	9	NA
LOPEZC	tot	0	100
ASOMAN	h w o	0	100
GALLEG	tot	0	100
KURAHA	s w c hw tot	5	90	Yes	Yes
PANDEY	c tot	0	NA		Yes
YANG	c tot	5	NA
OLIVOM	c	4	100	Yes
TSE	h w tot	9	100	Yes	Yes
LIANG	c tot	0	100
BRENNE	h w c tot	3	100		Yes
JIANG	tot	17	100	Yes
EPICC	c	10	NA		Yes
KIYOHA	s	0	100
HE	tot	9	88		Yes
LIM	h	0	96
LIN	tot	9	100		Yes
FERREC	c tot4	3	72
ALZOUG	s h w c tot	3	NA	Yes	Yes
GELAC	s h w hw tot	6	100		Yes
MASJED	s h w o tot	4	100	Yes
REN	tot	5	100
SEKI	s	7	94	Yes
WHIOS	h4 w4 c4 tot	0	0		4
ILCCO	h w c tot	3	100	Yes	Yes
TORRES	h	2	99		Yes

¹ETS exposure measures reported, coded as s: Spousal; h: Household; w: Work; c: Childhood; hw: Exposure at both home and work; tr: Travel; o: Social/other; tot: Total exposure. Codes marked 4 represent exposures for which the only result presented is a statement that no association was found;

²Number of factors adjusted for, excluding sex;

³Coded as yes: Dose response result presented;

⁴The only dose response result presented is a statement that no dose response was found. NA: Not available.

Table 3 Meta-analyses of smoking by the spouse (or nearest equivalent)

Estimates considered	No. of estimates	Relative risk (95% confidence limits)		Heterogeneity1
		Fixed-effects meta-analysis	Random-effects meta-analysis
All	119	1.18 (1.14-1.23)	1.21 (1.14-1.29)	+++
N America	38	1.08 (1.00-1.17)	1.09 (0.95-1.26)	+++
Europe	22	1.15 (1.03-1.28)	1.16 (1.00-1.35)	(+)
Asia	54	1.24 (1.17-1.32)	1.31 (1.20-1.44)	+++
Asia - Japan	13	1.26 (1.11-1.45)	1.26 (1.11-1.45)	NS
Asia - Hong Kong	8	1.32 (1.12-1.57)	1.31 (1.06-1.63)	NS
Asia - China	23	1.16 (1.06-1.27)	1.29 (1.08-1.54)	+++
Asia - Other	10	1.34 (1.19-1.51)	1.37 (1.19-1.57)	NS
Heterogeneity between Asian countries				NS
Other continents	5	1.20 (1.09-1.33)	1.20 (1.09-1.33)	NS
Heterogeneity between continents				(+)
Published in 1981-1989	34	1.38 (1.24-1.54)	1.38 (1.24-1.54)	NS
Published in 1990-1999	33	1.09 (1.01-1.17)	1.15 (1.02-1.28)	++
Published in 2000-2009	34	1.22 (1.12-1.33)	1.21 (1.08-1.36)	+
Published in 2010 onwards	18	1.17 (1.10-1.26)	1.13 (0.94-1.36)	+++
Heterogeneity by publication date				++
1-49 cases	23	1.44 (1.14-1.81)	1.47 (1.15-1.88)	NS
50-99	31	1.30 (1.14-1.47)	1.27 (1.08-1.50)	+
100-199	29	1.09 (1.00-1.19)	1.10 (0.96-1.26)	+++
200-399	22	1.33 (1.21-1.46)	1.32 (1.16-1.50)	+
400+	14	1.14 (1.07-1.20)	1.13 (1.02-1.25)	++
Heterogeneity by study size				++
Case-control	97	1.18 (1.13-1.23)	1.22 (1.13-1.31)	+++
Prospective	22	1.18 (1.05-1.33)	1.18 (1.05-1.33)	NS
Heterogeneity by study type				NS
Not age adjusted	21	1.34 (1.19-1.50)	1.42 (1.18-1.71)	+
Age adjusted	98	1.16 (1.11-1.21)	1.18 (1.10-1.26)	+++
Heterogeneity by age adjustment				NS
Dose-response results not reported	46	1.13 (1.06-1.21)	1.18 (1.06-1.31)	++
Only no dose-response stated	2	0.95 (0.60-1.50)	0.95 (0.60-1.50)	NS
Dose-response results reported	71	1.21 (1.15-1.28)	1.24 (1.14-1.35)	+++
Heterogeneity by dose response reporting				NS
Spouse the index	71	1.18 (1.11-1.24)	1.21 (1.12-1.31)	++
Spouse not the index	48	1.19 (1.12-1.27)	1.20 (1.07-1.35)	+++
Heterogeneity by index definition				NS

¹Significance levels indicated by +++ P < 0.001, ++ P < 0.01, + P < 0.05, (+) P < 0.1 for heterogeneity within level and for heterogeneity between level. NS: Not significant, P≥ 0.1.

Table 4 Meta-analyses of childhood environmental tobacco smoke exposure

Estimates considered	No. of estimates	Relative risk (95% confidence limits)		Heterogeneity1
		Fixed-effects meta-analysis	Random-effects meta-analysis
From any cohabitant	41	1.08 (1.01-1.15)	1.15 (1.02-1.29)	+++
N America	13	1.00 (0.89-1.13)	1.06 (0.89-1.28)	+
Europe	11	0.94 (0.81-1.08)	1.02 (0.81-1.29)	+
Asia	15	1.26 (1.11-1.42)	1.31 (1.02-1.67)	+++
Other	2	1.10 (0.95-1.28)	1.13 (0.89-1.45)	NS
Heterogeneity between continents				+
From mother specifically	9	0.96 (0.77-1.20)	0.98 (0.77-1.25)	NS
From father specifically	11	0.90 (0.80-1.00)	1.00 (0.78-1.29)	+++
From parents specifically	8	0.78 (0.64-0.94)	0.78 (0.64-0.94)	NS

¹Significance levels indicated by +++P < 0.001, ++P < 0.01, +P < 0.05, (+) P < 0.1 for heterogeneity within level and for heterogeneity between level. NS: Not significant, P≥ 0.1.

Table 5 Estimates used when adjusting for potential confounding effects¹

	Statistic	Fruit consumption	Vegetable consumption	Dietary fat consumption	Education
Lung cancer risk	N studies	14	16	6	12
	RR2	0.86	0.88	1.22	0.91
	(95%CI)	(0.78-0.96)8	(0.80-0.97)8	(1.09-1.36)8	(0.88-0.95)6
	per	SD	SD	SD	Year3
ETS exposure	N studies	11	16	12	13
at home	Difference24	-0.0737	-0.0568	0.1317	-0.5346
	(SE)	-0.02	-0.021	-0.032	-0.063
	unit	SD	SD	SD	Year3
Correlations5	Fruit consumption	1	+0.3147	-0.104NS	+0.143NS
	Vegetable consumption		1	-0.054NS	-0.1309
	Dietary fat consumption			1	-0.039NS
	Education				1

Note: P values are indicated by

⁶P < 0.001,

⁷P < 0.01,

⁸P < 0.05,

⁹P < 0.1, or

^NSP≥ 0.1. ¹All data are for lifelong non-smoking females;

²Based on random-effects meta-analysis;

³The SD for education was taken as 2.435 years based on six studies;

⁴Difference in level of confounder between those exposed and unexposed to ETS at home;

⁵Based on seven studies, using unweighted means.

Table 6 Adjusted/corrected analyses: Husband smoking¹

Studies	n	Unadjusted for confoundingUncorrected for misclassificationRR (95%CI)	Adjusted for confounding2Uncorrected for misclassificationRR (95%CI)	Adjusted for confounding2Corrected for misclassification3RR (95%CI)
All	93	1.219 (1.138-1.305)	1.139 (1.062-1.221)	1.077 (0.999-1.162)
North America	29	1.074 (0.937-1.232)	1.004 (0.873-1.154)	0.898 (0.775-1.039)
Europe and New Zealand	20	1.174 (1.007-1.369)	1.092 (0.934-1.277)	1.062 (0.899-1.254)
China (including Hong Kong and study LIM)	27	1.321 (1.144-1.524)	1.239 (1.071-1.433)	1.175 (1.005-1.374)
Rest of Asia (including study ILCCO)	17	1.284 (1.187-1.389)	1.194 (1.103-1.291)	1.164 (1.072-1.262)
North America, Europe and New Zealand	49	1.112 (1.004-1.231)	1.037 (0.935-1.150)	0.959 (0.858-1.072)
Asia	44	1.314 (1.199-1.439)	1.229 (1.121-1.348)	1.181 (1.070-1.304)
Published in 1980s	26	1.361 (1.216-1.522)	1.267 (1.132-1.417)	1.194 (1.059-1.347)
Published in 1990s	27	1.152 (1.016-1.305)	1.077 (0.948-1.225)	1.005 (0.871-1.160)
Published in 2000s	26	1.240 (1.105-1.392)	1.163 (1.034-1.308)	1.115 (0.987-1.260)
Published in 2010s	14	1.139 (0.945-1.372)	1.059 (0.877-1.277)	1.026 (0.844-1.247)
< 100 cases	49	1.339 (1.178-1.521)	1.249 (1.098-1.422)	1.192 (1.038-1.370)
100-199 cases	22	1.117 (0.973-1.284)	1.042 (0.904-1.200)	0.978 (0.846-1.131)
200-399 cases	13	1.363 (1.190-1.561)	1.275 (1.114-1.460)	1.226 (1.051-1.429)
400+ cases	9	1.101 (0.973-1.247)	1.027 (0.905-1.166)	0.957 (0.826-1.108)
With dose-response data4	24	1.308 (1.181-1.449)	1.226 (1.105-1.359)	1.170 (1.052-1.302)
Without dose-response data	69	1.182 (1.088-1.286)	1.104 (1.014-1.201)	1.040 (0.948-1.141)
With age adjustment5	75	1.184 (1.100-1.274)	1.106 (1.027-1.191)	1.048 (0.966-1.136)
Without age adjustment	18	1.437 (1.194-1.728)	1.340 (1.110-1.618)	1.264 (1.026-1.556)
Case-control studies	77	1.226 (1.133-1.326)	1.144 (1.057-1.239)	1.080 (0.990-1.177)
Prospective studies	16	1.187 (1.043-1.350)	1.111 (0.977-1.264)	1.064 (0.928-1.220)

¹All analyses use random-effects models;

²Adjusted for confounding by fruit, vegetables and dietary fat consumption and by education;

³Using the Lee and Forey method[22] with an additive model and assuming a concordance ratio of 3 and misclassification rates of 2.5% for studies in North America and Europe and 10% for studies in Asia;

⁴Specifically for smoking by the husband;

⁵Or matching (within nonsmokers).

Table 7 Adjusted/corrected analyses: Per 10 cigs smoked by husband¹

Studies	n	Unadjusted for confoundingUncorrected for misclassificationRR (95%CI)	Adjusted for confounding2Uncorrected for misclassificationRR (95%CI)	Adjusted for confounding2Corrected for misclassification3RR (95%CI)
All	93	1.102 (1.065-1.140)	1.062 (1.027-1.099)	1.032 (0.994-1.071)
North America	29	1.037 (0.977-1.101)	1.006 (0.946-1.070)	0.957 (0.896-1.022)
Europe and New Zealand	20	1.060 (0.995-1.128)	1.020 (0.956-1.088)	1.003 (0.938-1.073)
China (including Hong Kong and study LIM)	27	1.169 (1.082-1.263)	1.127 (1.041-1.219)	1.094 (1.006-1.191)
Rest of Asia (including study ILCCO)	17	1.142 (1.095-1.191)	1.094 (1.050-1.141)	1.079 (1.033-1.127)
North America, Europe and New Zealand	49	1.046 (1.001-1.094)	1.012 (0.967-1.059)	0.974 (0.928-1.023)
Asia	44	1.158 (1.104-1.216)	1.113 (1.060-1.170)	1.089 (1.033-1.147)
Published in 1980s	26	1.148 (1.092-1.207)	1.105 (1.052-1.162)	1.075 (1.019-1.134)
Published in 1990s	27	1.063 (1.004-1.125)	1.025 (0.967-1.087)	0.988 (0.926-1.053)
Published in 2000s	26	1.123 (1.056-1.194)	1.085 (1.020-1.155)	1.061 (0.995-1.132)
Published in 2010s	14	1.073 (0.970-1.188)	1.032 (0.932-1.143)	1.014 (0.912-1.128)
< 100 cases	49	1.143 (1.077-1.213)	1.101 (1.036-1.169)	1.072 (1.005-1.144)
100-199 cases	22	1.062 (0.993-1.137)	1.025 (0.957-1.098)	0.994 (0.926-1.066)
200-399 cases	13	1.176 (1.097-1.261)	1.134 (1.058-1.216)	1.111 (1.027-1.202)
400+ cases	9	1.041 (0.976-1.111)	1.002 (0.938-1.070)	0.966 (0.895-1.042)
With dose-response data4	24	1.123 (1.072-1.176)	1.082 (1.032-1.134)	1.053 (1.005-1.103)
Without dose-response data	69	1.091 (1.044-1.139)	1.053 (1.007-1.100)	1.021 (0.973-1.071)
With age adjustment5	75	1.084 (1.046-1.123)	1.044 (1.008-1.082)	1.015 (0.976-1.056)
Without age adjustment	18	1.211 (1.101-1.331)	1.168 (1.061-1.285)	1.131 (1.018-1.256)
Case-control studies	77	1.106 (1.064-1.150)	1.066 (1.025-1.109)	1.034 (0.991-1.080)
Prospective studies	16	1.081 (1.021-1.145)	1.043 (0.985-1.105)	1.018 (0.957-1.083)

¹All analyses use random-effects models;

²Adjusted for confounding by fruit, vegetables and dietary fat consumption and by education;

³Using the Lee and Forey method[22] with an additive model and assuming a concordance ratio of 3 and misclassification rates of 2.5% for studies in North America and Europe and 10% for studies in Asia;

⁴Specifically for smoking by the husband;

⁵Or matching (within nonsmokers).