Circulating enterolactone and risk of breast cancer: a prospective study in New York

Zeleniuch‐Jacquotte, Anne; Adlercreutz, Herman; Shore, Roy E.; Koenig, Karen L.; Kato, Ikuko; Arslan, Alan A.; Toniolo, Paolo

doi:10.1038/sj.bjc.6601893

Cited by 60 publications

(37 citation statements)

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“…The protective action of plant lignans against breast cancer in post-menopausal, but not in pre-menopausal women, would suggest that lignan activity has a physiologic effect only at low oestradiol levels. One of the mechanisms of action may be greater sex hormone-binding globulin production and binding of free oestradiol (Adlercreutz et al, 1989(Adlercreutz et al, , 1992Zeleniuch-Jacquotte et al, 2004;Low et al, 2007). Binding of type II nuclear oestrogen receptor (Adlercreutz et al, 1992;Adlercreutz, 2007) and altering oestrogen synthesis within the breast cells and extragonadal sites, such as the adipose tissue, are other possible mechanisms (Adlercreutz et al, 1993;Saarinen et al, 2007).…”

Section: Discussionmentioning

confidence: 99%

Lignans and breast cancer risk in pre- and post-menopausal women: meta-analyses of observational studies

et al. 2009

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Phyto-oestrogens are plant compounds structurally similar to oestradiol, which have been proposed to have protective effects against breast cancer. The main class of phyto-oestrogens in the Western diet is lignans. Literature reports on the effect of lignans in breast cancer risk have been conflicting. We performed three separate meta-analyses to examine the relationships between (i) plant lignan intake, (ii) enterolignan exposure and (iii) blood enterolactone levels and breast cancer risk. Medline, BIOSIS and EMBASE databases were searched for publications up to 30 September 2008, and 23 studies were included in the random effects meta-analyses. Overall, there was little association between high plant lignan intake and breast cancer risk (11 studies, combined odds ratio (OR): 0.93, 95% confidence interval (95% CI): 0.83 -1.03, P ¼ 0.15), but this association was subjected to marked heterogeneity (I 2 ¼ 44%). Restricting the analysis to post-menopausal women, high levels of plant lignan intake were associated with reduced breast cancer risk (7 studies, combined OR: 0.85, 95% CI: 0.78, 0.93, Po0.001) and heterogeneity was markedly reduced (I 2 ¼ 0%). High enterolignan exposure was also associated with breast cancer (5 studies, combined OR: 0.73, 95% CI: 0.57, 0.92, P ¼ 0.009) but, again, there was marked heterogeneity (I 2 ¼ 63%). No association was found with blood enterolactone levels (combined OR: 0.82, 95% CI: 0.59 -1.14, P ¼ 0.24). In conclusion, plant lignans may be associated with a small reduction in post-menopausal breast cancer risk, but further studies are required to confirm these results. (Beral, 2003) have both been associated with increased breast cancer risk. Isoflavones and lignans are plant compounds structurally similar to 17b-oestrodiol known as phyto-oestrogens, capable of oestrogen receptor binding (Kuiper et al, 1998;Mueller et al, 2004). Isoflavones are mostly found in soybean products, which are a staple of the Asian diet, whereas lignans are the principal group of phyto-oestrogens in Western diets. Lignans are more widespread in foods than isoflavones and are present in grain cereals, vegetables, seeds, tea and coffee (Mazur, 1998a;Mazur et al, 1998b). Microflora in the colon (Setchell et al, 1981) convert plant lignans into enterolignans, which are detectable in blood and urine. Their levels have been correlated with the amount of plant lignans ingested (Nesbitt et al, 1999).In a recent meta-analysis, an inverse dose-response relationship was shown between breast cancer risk and soy-food intake in Asian, but not in Western women (Wu et al, 2008). Lignans have been shown to exhibit anti-carcinogenic properties (Wang et al, 1994;Prasad 2000;Bergman Jungeström et al, 2007), and it is hypothesised that exposure to high levels may be associated with a reduction in breast cancer risk. However, results from a number of studies in Western populations have been variable. The aim of our systematic review was to establish whether an association exists between lignan exposure and breast cancer ris...

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Section: Discussionmentioning

confidence: 99%

Lignans and breast cancer risk in pre- and post-menopausal women: meta-analyses of observational studies

et al. 2009

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“…To increase our sample size, we included data from controls of a breast cancer case-control study nested within the NYUWHS, 26 which had a design very similar to the present study and for which enterolactone levels were measured in the same laboratory (Table V). After adjusting for body mass index, the only correlation observed was a weak negative correlation with estrone in controls (r 5 20.12), but not in cases (20.05).…”

Section: S)mentioning

confidence: 99%

Circulating enterolactone and risk of endometrial cancer

Zeleniuch‐Jacquotte

Lundin

Micheli

et al. 2006

Intl Journal of Cancer

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It has been suggested that phytoestrogens protect against hormone-dependent cancers. Lignans are the main class of phytoestrogens in Western diets. We conducted a prospective study of endometrial cancer and circulating levels of the main human lignan, enterolactone. The design was a case-control study nested within 3 prospective cohort studies, in New York, Sweden and Italy. Serum or plasma samples had been collected at enrollment and stored at 280°C. A total of 153 cases, diagnosed a median of 5.3 years after blood donation, and 271 matched controls were included. No difference in circulating enterolactone was observed between cases (median, 19.2 nmol/L) and controls (18.5 nmol/L). Adjusting for body mass index, the odds ratio for the top tertile of enterolactone, as compared to the lowest was 1.2 (95% CI, 0.7-2.0; p for trend 5 0.53). Lack of association was observed in both pre-and postmenopausal women. No correlation was observed between enterolactone and circulating estrogens or SHBG in healthy postmenopausal women. These results do not support a protective role of circulating lignans, in the range of levels observed, against endometrial cancer. ' 2006 Wiley-Liss, Inc.Key words: endometrial cancer; prospective study; nested casecontrol study; enterolactone; lignan; phytoestrogen It has been suggested that phytoestrogens (estrogenic compounds of plant origin) protect against hormone-dependent cancers. Estrogen-related mechanisms that have been proposed include competitive binding with estrogen receptors (ERs), resulting in an overall anti-estrogenic effect when estrogen concentrations are high because of the weak estrogenic potency of phytoestrogens as compared to estradiol; inhibition of aromatase (the enzyme responsible for the peripheral conversion of androgens into estrogens); and stimulation of the production of SHBG, resulting in reduced circulating free estradiol. [1][2][3][4][5] Phytoestrogens have also been reported to have antioxidant and antiproliferative properties which provide additional pathways through which they may reduce cancer risk. 6,7 The 2 main groups of phytoestrogens found in humans, the isoflavonoids and the lignans, are formed in the intestinal tract by transformation of plant precursors (isoflavone glycosides and plant lignans) by the microflora. Soy and soy products are the main sources of isoflavones, whereas lignans are found in oilseeds, in particular flaxseed, whole grain products, nuts, berries, legumes and some vegetables and fruits. 6,[8][9][10] Historically, lignans have been the main group of phytoestrogens in Western-type diets.Endometrial cancer is of particular interest when studying exposures thought to act through estrogen-related mechanisms because of the strong, direct association of both exogenous estrogens, such as estrogen replacement therapy, 11 and endogenous estrogens 12,13 with risk. We measured circulating enterolactone levels in subjects from a case-control study of endometrial cancer nested within 3 cohorts, the New York University Women's Health Study (...

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“…[14][15][16][17][18][19][20][21] Two recently published metaanalyses (including our own) showed that high serum or urinary enterolactone levels were associated with a nonsignificant reduced postmenopausal breast cancer risk, whereas high consumption of dietary lignans was associated with a significant reduced postmenopausal breast cancer risk. 22,23 The objective of our study was to examine the association of the major serum enterolignan (enterolactone) with the risk of postmenopausal breast cancer in a large German study population with Western dietary habits.…”

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confidence: 99%

Serum enterolactone and postmenopausal breast cancer risk by estrogen, progesterone and herceptin 2 receptor status

Zaineddin

Vrieling

Buck

et al. 2011

Intl Journal of Cancer

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Lignans are a group of estrogenic compounds present in plants. Several epidemiological studies proposed that lignans may protect against breast cancer by exerting anticarcinogenic activity. Levels of enterolactone were determined in serum samples of 1,250 cases and 2,164 controls from a large population-based case-control study. We assessed the association between serum enterolactone and postmenopausal breast cancer risk using conditional logistic regression accounting for potential risk and confounding factors. Fractional polynomials were used to determine the function that best fitted the data. Moreover, we assessed heterogeneity by estrogen/progesterone/herceptin (ER/PR/HER2) status of the tumor. Additionally, a meta-analysis with seven further studies addressing enterolactone concentrations and breast cancer risk was performed. Postmenopausal breast cancer risk decreased with increasing serum enterolactone levels [highest compared to lowest quintile: [odds ratio 5 0.65; 95% confidence interval (CI) 0.52-0.83, p trend 5 <0.0001]. A significant inverse association for ER1/PR1 as well as ER2/PR2 tumors was observed, with a significantly stronger association for ER2/PR2 tumors (p heterogeneity 5 0.03). The association for ER2/PR2 tumors did not differ by expression of HER2 (p heterogeneity 5 0.3). The meta-analysis yielded a significant reduced pooled risk estimate of: 0.66; 95% CI: 0.55-0.77) comparing the highest to the lowest quantiles of enterolactone levels. We found strong evidence for a significant inverse association between serum enterolactone and postmenopausal breast cancer risk, which was stronger for ER2PR2 than for ER1PR1 tumors but not differential by further expression of HER2. The overall evidence together with other studies supports an inverse association between higher serum enterolactone levels and postmenopausal breast cancer risk.Phytoestrogens are a group of biologically active compounds that have been shown to protect against hormone-dependent cancers, in particular, breast cancer. 1-4 Their protective inverse association with breast cancer may be due to either estrogenic or antiestrogenic properties. [5][6][7][8] Because of their chemical structure, phytoestrogens can compete with endogenous estrogen for binding to the estrogen receptor (ER) of the tumor, thereby plausibly reducing the hormonal effect of the endogenous estrogens. 9 In addition to this, phytoestrogens also have antioxidative and antiproliferative properties and thereby may also reduce cancer risk. 10 The two main groups of phytoestrogens are the isoflavones and the lignans. Isoflavones, in particular, genistein, are mostly found in soy products. Only a few nonsoy plants contain isoflavones (e.g., legumes, grapefruit and raisins); but, at lower concentration, isoflavones do not importantly contribute to phytoestrogen intake in Western diets. 11,12 Plant lignans are widely present in whole grain, berries, vegetables, fruits, flaxseeds and other types of seeds and are the main source of phytoestrogens in Western populations....

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Circulating enterolactone and risk of breast cancer: a prospective study in New York

Cited by 60 publications

References 53 publications

Lignans and breast cancer risk in pre- and post-menopausal women: meta-analyses of observational studies

Lignans and breast cancer risk in pre- and post-menopausal women: meta-analyses of observational studies

Circulating enterolactone and risk of endometrial cancer

Serum enterolactone and postmenopausal breast cancer risk by estrogen, progesterone and herceptin 2 receptor status

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