Veggies vs lung cancer

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Hi All,

It seems that cruciferous vegetable protect us from lung cancer, irrespective of

whether we smoke. Cabbage or broccoli and brussel sprouts seemed to protect

similarly and independently.

Genes regulating the enzymes metabolizing the goodies in cruciferous vegetable

may

play a role, it seems, as stated by:

" These results provide strong evidence for our a-priori hypothesis that the

protective effect of cruciferous vegetables is most apparent in those who have

low

values of circulating GST enzymes " .

See the pdf-available below paper.

Effect of cruciferous vegetables on lung cancer in patients stratified by

genetic

status: a mendelian randomisation approach

Lancet 366, Iss 9496, 29 Oct 2005-4 Nov 2005, 1558-1560

Brennan, C Hsu, Norman Moullan, Neonilia Szeszenia-Dabrowska,

Jolanta

Lissowska, Zaridze, Rudnai, Eleonora Fabianova, Dana Mates, Vladimir

Bencko et al.

Summary

Whether consumption of cruciferous vegetables protects against lung cancer is

unclear, largely because of potential confounding factors. We therefore studied

the

role of cruciferous vegetables in lung cancer after stratifying by GSTM1 and

GSTT1

status, two genes implicated in the elimination of isothiocyanates, the likely

chemopreventative compound. In 2141 cases and 2168 controls, weekly consumption

of

cruciferous vegetables protected against lung cancer in those who were GSTM1

null

(odds ratio=0·67, 95% CI 0·49–0·91), GSTT1 null (0·63, 0·37–1·07), or both

(0·28,

0·11–0·67). No protective effect was seen in people who were both GSTM1 and

GSTT1

positive (0·88, 0·65–1·21). Similar protective results were noted for

consumption of

cabbage and a combination of broccoli and brussels sprouts. These data provide

strong evidence for a substantial protective effect of cruciferous vegetable

consumption on lung cancer.

Observational studies have provided consistent evidence for a protective role of

vegetable consumption against lung cancer, with the evidence being most apparent

for

green cruciferous vegetables such as broccoli and cabbage.1 Such vegetables are

rich

in isothiocyanates, which have been shown in animals to have strong

chemopreventative properties against lung cancer.2 In a review of studies of the

effect of cruciferous vegetables, a definite protective effect against any type

of

cancer could not be identified, in view of the small size of studies and

potential

for confounding from other dietary sources.3

Confounding could, however, be addressed by adoption of a mendelian

randomisation

approach.4 Isothiocyanates are thought to be eliminated by

glutathione-S-transferase

enzymes, most notably GSTM1 and GSTT1.5 and 6 Both GSTM1 and GSTT1 genes have

null

alleles with homozygous null genotypes, resulting in no enzyme being produced.

Individuals who are homozygous for the inactive form of either or both genes

probably have higher isothiocyanate concentrations because of their reduced

elimination capacity. Furthermore, and implicit in the mendelian randomisation

approach, the roles of GSTM1 and GSTT1 genes are likely to be independent of

other

dietary and lifestyle factors, reducing the possibility of confounding from

these

sources.

.... a case-control study of 2141 cases and 2168 controls in ... a region that

has

traditionally high rates of cruciferous vegetable consumption. Incident cases

and

age-sex matched hospital or population controls ... the questionnaire listed 23

foods, of which three were cruciferous vegetables (cabbage and a combination of

brussels sprouts with broccoli). ...

Neither GSTM1 nor GSTT1 were related to potential confounding factors in the

controls, such as country, age, smoking status, education, and dietary variables

including cruciferous vegetable consumption (webtable 1). As expected,

cruciferous

vegetable consumption was related to other dietary variables, such as fruit and

other vegetables, and smoking status (webtable 2), although these associations

do

not detract from the validity of the mendelian randomisation comparison. ...

An overall protective effect was seen for consumption of cruciferous vegetables

at

least once a week compared with less than monthly (adjusted odds ratio=0·78, 95%

CI

0·64–0·96), which was much the same for both cabbage consumption and for

broccoli

and brussels sprout consumption (table 1). When stratified by GST status, any

protective effect of high consumption was restricted to those who were null for

GSTM1 (0·67, 0·49–0·91), GSTT1 (0·63, 0·37–1·07), or both GSTM1 and GSTT1,

(0·28,

0·11–0·67). No protective effect was seen in those who were GSTM1 and T1

positive,

with a moderate non-significant protective effect for those who had only one

null

genotype (0·80, 0·60–1·08). The interaction between GSTM1 null/GSTT1 null versus

other GSTM1/GSTT1 groups and cruciferous vegetable consumption was significant

(p=0·03). Similar results were observed separately for cabbage and

broccoli/brussels

sprout consumption, after adjustment for the other, suggesting an independent

protective effect of both sources of cruciferous vegetables.

Table 1. Odds ratios for lung cancer by cruciferous vegetable consumption* and

GST

status

===================

All cruciferous vegetables Cabbage Broccoli and brussel sprouts

Cases/controls* OR (95% CI) † p Cases/controls* OR (95% CI) †‡ p

Cases/controls*

OR (95% CI) †§** p

===================

ALL GST types

Low 327/250 1 367/296 1 1747/1758 1

Medium 677/754 0·77 (0·62–0·95) 0·0156 668/740 0·80 (0·65–0·98) 0·0342 249/261

1·04

(0·84–1·29) 0·7163

High 1137/1164 0·78 (0·64–0·96) 0·0188 1106/1132 0·83 (0·69–1·01) 0·0674 145/149

0·87 (0·66–1·14) 0·3118

GSTM1+

Low 160/140 1 177/159 1 842/885 1

Medium 323/368 0·92 (0·68–1·24) 0·5722 319/365 0·92 (0·69–1·24) 0·5996 127/134

1·08

(0·80–1·46) 0·6075

High 560/589 0·89 (0·67–1·18) 0·4156 547/573 0·93 (0·70–1·22) 0·5818 74/78 0·94

(0·64–1·39) 0·7695

GSTM1 null

Low 161/103 1 184/128 1 845/801 1

Medium 330/352 0·65 (0·47–0·89) 0·0072 323/342 0·69 (0·51–0·93) 0·0143 113/117

0·98

(0·71–1·35) 0·9122

High 531/531 0·67 (0·49–0·91) 0·0092 515/516 0·73 (0·55–0·97) 0·0308 64/68 0·72

(0·47–1·09) 0·1198

GSTT1+

Low 265/211 1 298/247 1 1443/1467 1

Medium 557/614 0·80 (0·63–1·01) 0·0631 546/607 0·81 (0·64–1·01) 0·0630 211/216

1·09

(0·87–1·38) 0·4475

High 953/971 0·83 (0·66–1·03) 0·0940 931/942 0·86 (0·70–1·06) 0·1635 121/113

0·97

(0·71–1·32) 0·8317

GSTT1 null

Low 58/37 1 65/46 1 285/270 1

Medium 115/133 0·67 (0·39–1·16) 0·1551 117/127 0·79 (0·47–1·33) 0·3707 33/41

0·80

(0·45–1·44) 0·4593

High 167/174 0·63 (0·37–1·07) 0·0849 158/171 0·73 (0·44–1·21) 0·2223 22/33 0·55

(0·27–1·11) 0·0954

GSTM1/GSTT1 +/+

Low 127/114 1 140/129 1 693/753 1

Medium 263/305 0·87 (0·62–1·22) 0·4100 259/306 0·87 (0·63–1·21) 0·4111 106/109

1·15

(0·82–1·59) 0·4191

High 471/502 0·88 (0·65–1·21) 0·4391 462/486 0·93 (0·69–1·27) 0·6584 62/59 1·02

(0·67–1·57) 0·9163

GSTM1+/GSTT1 null or GSTM1 null/GSTT1+

Low 162/117 1 186/140 1 828/774 1

Medium 325/339 0·82 (0·60–1·12) 0·2214 316/328 0·81 (0·60–1·10) 0·1756 112/120

0·97

(0·70–1·33) 0·8425

High 516/507 0·80 (0·60–1·08) 0·1498 501/495 0·81 (0·61–1·07) 0·1339 63/69 0·81

(0·53–1·24) 0·3362

GSTM1 null/GSTT1 null

Low 28/10 1 31/15 1 147/138 1

Medium 60/69 0·26 (0·10–0·63) 0·0032 62/67 0·37 (0·16–0·84) 0·0169 17/18 0·91

(0·39–2·13) 0·8273

High 87/92 0·28 (0·11–0·67) 0·0045 82/89 0·42 (0·19–0·94) 0·0338 11/15 0·35

(0·12–1·01) 0·0529

=======================

Null=those with homozygous deletion of GST. +=positive. Low=these vegetables

eaten less than once per month; medium=less than once per week; high=at least

once

per week.

* 2141 cases, 2168 controls.

† Adjusted by age, sex, country, education, and tobacco pack-years.

‡ Additional adjustment for intake of broccoli and brussels sprouts.

§** Additional adjustment for cabbage intake.

When the population was stratified by smoking history (never vs ever), the

protective effect in never smokers was largely independent of GSTM1 and GSTT1

status, being recorded in those who were positive for both M1 and T1 (0·31,

0·14–0·70) and negative for M1 and T1 (0·12, 0·01–1·54) (table 2). No

interaction

was noted for GSTM1/GSTT1 null versus other GSTM1/GSTT1 combinations in never

smokers (p=0·70), although there was evidence of interaction in those who had

smoked

(p=0·05). Since one might expect GST enzyme concentrations to be higher in

smokers

than in non-smokers because of the presence of tobacco-specific substrates,

GSTM1

and GSTT1 might not modify the protective effect of cruciferous vegetables in

non-smokers.

Table 2. Odds ratios for lung cancer by cruciferous vegetable consumption and

GSTM1

and GSTT1 status for ever and never smokers

====================== Never smokers Ever smokers

Case/control* OR † (95%CI) p Case/control ‡ OR §** (95%CI) p

======================

GSTM1+

Low 14/36 1 146/104 1

Medium 28/136 0·52 (0·23–1·18) 0·1165 295/232 1·01 (0·73–1·40) 0·9403

High 39/216 0·36 (0·16–0·79) 0·0107 521/373 1·04 (0·77–1·40) 0·8098

GSTM1 null

Low 11/27 1 150/76 1

Medium 25/121 0·57 (0·23–1·42) 0·2258 305/231 0·68 (0·48–0·96) 0·0300

High 39/172 0·47 (0·19–1·14) 0·0951 492/359 0·70 (0·50–0·96) 0·0288

GSTT1+

Low 22/56 1 243/155 1

Medium 49/219 0·56 (0·30–1·05) 0·0687 508/395 0·86 (0·66–1·10) 0·2323

High 68/340 0·40 (0·22–0·74) 0·0035 885/631 0·91 (0·72–1·16) 0·4607

GSTT1 null

Low 3/10 1 55/27 1

Medium 8/49 0·44 (0·07–2·84) 0·3857 107/84 0·71 (0·39–1·29) 0·2639

High 13/55 0·22 (0·03–1·56) 0·1303 154/119 0·65 (0·37–1·14) 0·1332

M1/T1 +/+

Low 14/30 1 113/84 1

Medium 23/110 0·47 (0·20–1·09) 0·0792 240/195 0·98 (0·69–1·41) 0·9337

High 29/182 0·31 (0·14–0·70) 0·0048 442/320 1·07 (0·77–1·50) 0·6806

M1/T1 +/null or null/+

Low 8/30 1 154/87 1

Medium 27/123 0·84 (0·31–2·25) 0·7307 298/216 0·85 (0·61–1·18) 0·3314

High 44/176 0·70 (0·27–1·83) 0·4649 472/331 0·81 (0·59–1·12) 0·2024

M1/T1 null/null

Low 3/3 1 25/7 1

Medium 3/22 0·09 (0·01–0·99) 0·0488 57/47 0·30 (0·11–0·81) 0·0176

High 4/22 0·12 (0·01–1·54) 0·1039 83/70 0·31 (0·12–0·82) 0·0176

========================

Null=those with homozygous deletion of GST. Low=less than once per month;

medium=less than once per week; high=at least once per week.

* 164 cases, 739 controls.

† In never smokers, model adjusted by age, sex, and education.

‡ 1977 cases, 1429 controls.

§** Adjusted by age, sex, country, education, and tobacco pack-years.

These results provide strong evidence for our a-priori hypothesis that the

protective effect of cruciferous vegetables is most apparent in those who have

low

values of circulating GST enzymes, because they have null alleles for GSTM1 and

GSTT1 genes. The results also accord with those of several smaller studies of

lung

cancer, breast cancer, and colorectal adenomas, which showed a protective effect

in

GSTM1 and GSTT1 null carriers.2 However, we cannot draw definitive conclusions

from

these individual studies because of their small sample size (the three previous

studies of lung cancer, based in Shanghai, Singapore, and Texas, consisted of a

total of 968 cases and 1362 controls).5, 8 and 9 Taking into consideration the

size

of the protective effects that have been reported in this and other studies,

which

are likely to have been substantially diluted by measurement error, these

findings

raise the prospect of an important chemopreventive effect against lung cancer

for

cruciferous vegetables in general, and isothiocyanates in particular.

Al Pater, PhD; email: old542000@...

__________________________________

- PC Magazine Editors' Choice 2005

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