introduction
Stomach cancer is the fourth most common cancer and the second most common cause of cancer death worldwide [
1]. The huge geographic and gender discrepancies (gastric cancer being eight times more common among Asian men than among North American women) indicate the importance of lifestyle and environmental factors, as well as the potential for prevention through change in exposures. Prevention opportunities are particularly important, given the dismal overall prognosis and the nature of the disease making early diagnosis rare [
2,
3]. Since
Helicobacter pylori infection was proposed as a necessary cause of noncardia gastric cancer [
4–
6] through inflammation and oxidative stress [
7–
9], the role of bioactive redox substances has emerged as highly relevant. While contrasting results from intervention trials have cast doubt on the positive influence of antioxidants on human health [
10] and gastric cancer prevention [
11,
12], only a few antioxidants (mainly β-carotene, vitamins A, C and E), out of the hundreds present in plant foods, have actually been investigated thoroughly.
In a recent study, we measured a marker of antioxidant function, the total radical-trapping antioxidant potential (TRAP) of plant foods, and we showed that a diet with high total antioxidant capacity (TAC) was associated with >30% reduction in gastric cancer risk [13]. The risk reduction was even stronger among individuals whose gastric mucosa was likely to be under oxidative stress, i.e. long-term smokers and those infected with
H. pylori [
13]. Still, only some of the reduced cancer risk could be attributed to vitamins C and E and β-carotene, while a significant part remained unexplained [
14].
Since flavonoids are major determinants of the in vitro TAC of plant products [15, 16], some of the preventive effect of plant foods on gastric tumors could be attributable to quercetin, a main dietary source of flavonoids [17], despite contradictory evidence from other cancer studies [
18–
21]. Quercetin not only possess strong antioxidant properties through free radical scavenging [
15] but also reduces inflammation and inhibits cell proliferation and angiogenesis [
22].
Thus, we investigated the association between quercetin dietary intake and gastric cancer risk using data from a large population-based case–control study conducted in Sweden, with detailed information both on known important covariates and on gastric cancer subtypes.