Flavonoids comprise the most common group of plant polyphenols and provide much of the flavor and color to fruits and vegetables. More than 5000 different flavonoids have been described. The six major subclasses of flavonoids include the flavones (e.g., apigenin, luteolin), flavonols (e.g., quercetin, myricetin), flavanones (e.g., naringenin, hesperidin), catechins or flavanols (e.g., epicatechin, gallocatechin), anthocyanidins (e.g., cyanidin, pelargonidin), and isoflavones (e.g., genistein, daidzein). Most of the flavonoids present in plants are attached to sugars (glycosides), although occasionally they are found as aglycones. Interest in the possible health benefits of flavonoids has increased owing to their potent antioxidant and free-radical scavenging activities observed in vitro. There is growing evidence from human feeding studies that the absorption and bioavailability of specific flavonoids is much higher than originally believed. However, epidemiologic studies exploring the role of flavonoids in human health have been inconclusive. Some studies support a protective effect of flavonoid consumption in cardiovascular disease and cancer, other studies demonstrate no effect, and a few studies suggest potential harm. Because there are many biological activities attributed to the flavonoids, some of which could be beneficial or detrimental depending on specific circumstances, further studies in both the laboratory and with populations are warranted.

We examined the association between whole-grain intake and incident upper aerodigestive tract cancer in a cohort of 34,651 postmenopausal, initially cancer-free women. We also studied established risk factors for upper aerodigestive cancers, including fruit and vegetable intake, smoking and alcohol intake. A mailed questionnaire at baseline in 1986 included a food-frequency questionnaire and assessment of other cancer risk factors. During the 14-year follow-up period, 169 Studies that have considered the role of dietary factors with regard to cancers of the upper aerodigestive tract have generally reported inverse associations with intake of fruit and vegetables, 1-7 and whole grains. 8,9 Several studies support the idea that wholegrain intake is associated with reduced risk of gastric cancers. 10 Studies that included grain fiber as a predictor 11,12 further bolster the idea that whole grain may protect against upper aerodigestive tract cancers. Previous studies of upper aerodigestive cancers have been case-control in design and, therefore, potentially subject to recall bias.The mechanism of the apparent protective effect of fruits, vegetables and whole grains against upper aerodigestive cancers remains unclear. It may be a result of their fiber content, antioxidant content or some other phytochemicals. Clarification of the protective mechanisms of fruits, vegetables and whole grains is important to our understanding of cancers of the upper aerodigestive tract. In an analysis of the Iowa Women's Health Study (IWHS), a prospective cohort study of initially 55-to 69-year old women living in Iowa, Zheng et al. 13 reported lower dietary intake of yellow/orange vegetables and of carotene, vitamins C and E and retinol in the 59 women who developed upper digestive tract cancers between 1986 and 1992.Our primary focus was to study whether, after 14 years of follow-up in the IWHS, whole-grain intake is related to reduced risk of upper aerodigestive tract cancers. At the same time, we reviewed evidence for the established lifestyle risk factors: low fruit and vegetable intake, smoking and alcohol intake. To address potential mechanisms, we considered the roles of fiber and specific micronutrients in the risk of upper digestive tract neoplasms. MATERIAL AND METHODSA detailed description of the methodology of the IWHS has been published elsewhere. 14 Briefly, participants in the IWHS were a random sample of women aged 55-69 years from the 1985 Iowa driver's license list. A total of 41,836 women responded to a mail survey in January 1986 (42.7% response rate). Using information from the driver's license list and the 1980 U.S. census, it was determined that responders were about 3 months older than nonresponders, 0.4 kg/m 2 lighter and slightly more likely to live in rural, less affluent counties. Nonresponders had somewhat higher rates of smoking-related diseases. 14 Women were excluded from the analysis if they left 30 or more items blank on the foodfrequency questionnaire or reported implausibly high or low energy intak...

We examined whether there is an association between whole grain intake and incident endometrial cancer and whether the association varied by use of hormone replacement therapy. The study included 23,014 Iowa women, aged 55-69 years in 1986. A mailed food frequency questionnaire was used to estimate grain intake, hormone replacement therapy use, and other cancer risk factors. Cancer incidence from 1986 to 1998 was also collected. In analyses stratified by hormone replacement therapy use, an inverse association between whole grain intake and endometrial cancer was observed among never-users of hormone replacement therapy (p for trend = 0.05). Never-users in the highest quintile of whole grain intake were 0.63 times as likely to develop endometrial cancer as those in the lowest quintile of whole grain intake (95% confidence interval = 0.39-1.01). Among hormone replacement therapy users, no association between whole grain intake and endometrial cancer was evident. There was no statistically significant association between whole grain intake and incident endometrial cancer when users of hormone replacement therapy and nonusers were analyzed together. There also was no association between refined grain intake and endometrial cancer. Whole grain intake may protect against endometrial cancer among never-users of hormone replacement therapy.

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