Lignan Formation in Man—microbial Involvement and Possible Roles in Relation to Cancer

Setchell, Kenneth D.R.; Borriello, S. P.; Gordon, Helmut A.; Lawson, A. M.; Harkness, R. A.; Morgan, David M. L.; Kirk, D. N.; Adlercreutz, Herman; Anderson, Lora; Axelson, Magnus

doi:10.1016/s0140-6736(81)90250-6

Cited by 270 publications

(136 citation statements)

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“…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).…”

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

et al. 2009

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“…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.…”

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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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“…Recent case -control (Velicer et al, 2004) and cohort (Knekt et al, 2000) studies have suggested that use of antibiotics may increase the risk of breast cancer (Knekt et al, 2000;Velicer et al, 2004). A mechanism for any causal association is unknown, but it has been hypothesised that antibiotics may affect the ability of intestinal microflora to metabolise phytochemicals from edible plants into compounds that may protect against cancer (Setchell et al, 1981;Velicer et al, 2003). Since antibiotics are commonly used and breast cancer is common, any increased risk has major public health potential.…”

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Use of antibiotics and risk of breast cancer: a population-based case–control study

et al. 2004

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We examined the use of antibiotics among 2728 women with a first diagnosis of breast cancer during 1994 -2003, and 27 280 population controls in North Jutland County, Denmark, based on hospital discharge diagnoses, prescription use from 1989 to 2002, and population registry data. We found no increased relative risk of breast cancer associated with use compared with nonuse. The odds ratio for breast cancer associated with more than 10 prescriptions for antibiotics was 1.00 (95% CI 0.86 -1.15). Relative risks were similar for different classes of antibiotics. A subanalysis based on cases and controls younger than 70 years of age, with data on first birth and number of children, showed similar risk estimates even after adjustment for age at first birth and parity. In our study, use of antibiotics was not associated with an increased risk of breast cancer.

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Lignan Formation in Man—microbial Involvement and Possible Roles in Relation to Cancer

Cited by 270 publications

References 22 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

Use of antibiotics and risk of breast cancer: a population-based case–control study

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