Fiber, Estrogen and Breast Cancer in Mexican American Women

Institution: University of Southern California
Investigator(s): Malcolm  Pike , Ph.D. -
Award Cycle: 2002 (Cycle VIII) Grant #: 8WB-0066 Award: $159,117
Award Type: STEP Award
Research Priorities
Prevention & Risk Reduction>Other searches for the causes



Initial Award Abstract (2002)
There is a large and compelling body of evidence (both epidemiological and experimental) implicating estrogen in the cause of human breast cancer. The role of diet in breast cancer risk is less clear. However, there is evidence to suggest that dietary fiber may play an important role in estrogen metabolism and may therefore be an important determinant of circulating estrogen levels in the body. Thus, understanding the biological relationship between dietary fiber intake and estrogen metabolism may provide some insight in how diet may alter a woman's risk of breast cancer.

We propose to investigate the hypothesis that high intake of dietary fiber, either total or a specific fraction (e.g., soluble fiber from legumes or insoluble fiber from grain), lowers estrogen levels in the body and thus lowers a woman's risk of breast cancer. We will be examining this hypothesis among a group of Mexican American Latinas currently enrolled in an ongoing research study. These women are a scientifically important group to study, because they have the lowest breast cancer rates of any major racial/ethnic group in the US, and their dietary fiber intake is higher than what is reported by other racial/ethnic groups.

Two generations of Mexican-origin postmenopausal women numbering nearly 7,000 are currently enrolled in an ongoing cohort study. Baseline data on dietary fiber have been collected and blood and urine specimens are currently being collected as part of an NIH funded grant. No additional subject recruitment will be required for this proposed study. We will compare dietary fiber intake, quantified from both a food frequency questionnaire and from a biochemical marker of intake, with blood hormone levels. An updated food frequency questionnaire will be administered at the time of blood draw to obtain current dietary information.

Epidemiology studies examining dietary fiber and breast cancer risk are equivocal. Investigators have proposed that the reason may be due to the heterogeneous nature of dietary fiber, differences in ways fiber is measured and quantified, or the magnitude of fiber intake in the populations studied. This study is innovative in that it (1) utilizes an ideal population where the traditional diet is rich in dietary fiber; (2) comprises two generations of Mexican origin women where differences in breast cancer rates provide powerful evidence on the extent to which the causes are due to changes in environmental factors; and (3) utilizes two methods of quantifying fiber intake - that of a food frequency questionnaire as well as a biochemical marker.


Final Report (2004)
There is a large and compelling body of evidence implicating estrogen in the cause of human breast cancer. The role of diet in breast cancer risk is less clear. There is evidence to suggest that dietary fiber may play an important role in estrogen metabolism and may be an important determinant of circulating estrogen levels in the body. Understanding the biological relationship between dietary fiber intake and estrogen metabolism may provide some insight in how diet may alter a woman's risk of breast cancer.

This study investigated the hypothesis that high dietary fiber intake, either total or a specific fraction (e.g., soluble or insoluble non-starch polysaccharides (NSP) or total lignan), lowers circulating estrogen levels. We investigated this hypothesis among Latinas of Mexican origin enrolled in "The Multiethnic/Minority Cohort Study of Diet and Cancer." Women, who were aged 45-64 at cohort entry, reported never having used menopausal hormone therapy (HT) and reported being postmenopausal on the baseline questionnaire, were eligible for selection. The dietary fiber value from the baseline food frequency questionnaire (FFQ) was used to further define subjects for inclusion to ensure a sufficient number of subjects in both the high and low comparison groups. Subjects agreeing to participate in this sub-study were asked to provide a blood specimen as well as fill out a second complete FFQ in order to provide current dietary information concurrent with blood collection. Plasma levels of enterolactone and genistein were measured in the Folkhalsan Research Center laboratory at the University of Helsinki, Finland and serum hormone assays were conducted in the Reproductive Endocrine Research Laboratory at USC.

Blood specimens from 353 Latina women who met the inclusion criteria for the study were included in laboratory assays. The first aim of this study was to determine the effect of dietary fiber intake on blood concentration levels of estrone (E1), estradiol (E2), and sex-hormone-binding globulin (SHBG). Dietary fiber intake was quantified in two ways: (1) from the FFQ administered at time of blood draw; and (2) from biomarkers of dietary fiber intake, i.e., the lignan enterolactone (Enl) and the isoflavone genistein. We found that measures of dietary fiber intake, quantified from the FFQ administered at time of blood draw, as well as the biomarkers Enl and genistein were significantly associated with serum hormone levels. As predicted, serum E1 and E2 levels decreased, as did bioavailable E2, as dietary fiber intake increased. These associations remained after adjusting for weight, even though weight strongly influenced the blood levels of E1, E2, bioavailable E2, SHBG, and fiber in opposite directions. This provides strong evidence of an association between dietary fiber intake and circulating hormone levels in postmenopausal women. We are continuing to investigate these associations to learn which component of dietary fiber, e.g., insoluble fiber from grain or soluble fiber from legumes, has the strongest influence.

A secondary aim of this study was to investigate the correlations between plasma Enl and genistein with various measures of dietary fiber intake measured by the FFQ. We found a statistically significant positive correlation (0.14) between plasma Enl and the lignan secoisolariciresinol quantified from the FFQ. Plasma genistein was significantly correlated with dietary fiber (0.18), soluble NSP (0.16), insoluble NSP (0.18), and the lignan secoisolariciresinol (0.14).

This study provides an exceptional opportunity to understand the biological relationship between dietary fiber and estrogen metabolism and potentially provides a dietary mechanism for lowering a woman's risk of breast cancer.


Symposium Abstract (2007)
New findings stemming from our previously funded CBCRP research suggests that grapefruit intake may be associated with an increased risk of breast cancer among postmenopausal women.

The inhibitory effect of grapefruit juice on the intestinal cytochrome P450 3A4 enzyme system was discovered accidentally in 1989 during a study designed to test the effect of ethanol on a calcium-channel blocker. Grapefruit juice was given to subjects to mask the taste of the ethanol. Subsequent investigations have found that grapefruit interacts with more than 60% of orally administered drugs leading to elevation of serum concentrations. An effect is seen with the whole fruit as well as the juice and chronic consumption may enhance the magnitude of the effect.

Since 1989, the list of drug interactions with grapefruit juice has expanded to include oral estradiol and progesterone. U.S. Food and Drug Administration (FDA) mandated labeling for estrogen and estrogen-progestin products for postmenopausal women now contains warnings that grapefruit juice may increase plasma concentrations of estrogens. Since endogenous estrogens are metabolized in the same manner as exogenous estrogens, we conducted a study to determine whether endogenous levels were significantly affected by grapefruit consumption. We found a statistically significant positive association between whole grapefruit intake (we had no information on grapefruit juice intake) and endogenous serum estrogen level among 242 naturally postmenopausal Latina women not taking menopausal hormone therapy.

Since it is well established that serum estrogen concentration is associated with postmenopausal breast cancer risk, it is plausible that regular intake of grapefruit would increase a woman’s risk of breast cancer. Therefore, we recently investigated whole grapefruit intake in association with breast cancer risk among postmenopausal women in the Hawaii-Los Angeles Multiethnic Cohort Study, a prospective cohort that includes over 50,000 postmenopausal women from five racial/ethnic groups. A total of 1,657 incident breast cancer cases were available for analysis.

Grapefruit intake was significantly associated with an increased risk of breast cancer (relative risk (RR)=1.30, 95% confidence interval (CI) 1.06-1.58) for subjects in the highest category of intake, i.e., one-quarter grapefruit or more per day, compared to non-consumers (ptrend = 0.015). The relative risk of breast cancer associated with consumption of ¼ grapefruit or more per day compared to non-consumers was 44% higher among women who had never used hormone therapy; 36% higher in current estrogen therapy users, and 27% higher among current estrogen+progestin therapy users. The risk of breast cancer associated with consumption of grapefruit was 32% higher among lean/normal weight women and 26% higher among overweight/obese women. Taken together, these results suggest that the risk of breast cancer associated with grapefruit intake is stronger for subgroups of women with lower circulating estrogen levels.

To our knowledge, this was the first report of a commonly consumed food that may increase the risk of breast cancer. If confirmed, these new findings have important public health implications.