Phytoestrogen Exposure Is Associated with Circulating Sex Hormone Levels in Postmenopausal Women and Interact with<i>ESR1</i>and<i>NR1I2</i>Gene Variants

Low, Yen-Ling; Dunning, Alison M.; Dowsett, Mitch; Folkerd, Elizabeth; Doody, Deborah; Taylor, James I.; Bhaniani, Amit; Luben, Robert; Khaw, Kay‐Tee; Wareham, Nick; Bingham, Sheila

doi:10.1158/1055-9965.epi-06-0899

Cited by 55 publications

(33 citation statements)

References 58 publications

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“…In postmenopausal women, an interaction effect between NR1I2 gene variants and phytoestrogen exposure has been reported to influence circulating sex hormone levels. 37 Our observation here that the heterozygous rs247280 genotype AG of NR1I2 is linked with an increased risk for CO in the JPN study group is consistent with this hypothesis. However, no significant association between CYP3A4 gene variants and risk of CO was found in this study.…”

Section: Discussionsupporting

confidence: 88%

Association of variants in genes involved in environmental chemical metabolism and risk of cryptorchidism and hypospadias

et al. 2012

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We hypothesized that single-nucleotide polymorphisms (SNPs) of genes involved in environmental endocrine disruptors (EEDs) metabolism might influence the risk of male genital malformations. In this study, we explored for association between 384 SNPs in 15 genes (AHR, AHRR, ARNT, ARNT2, NR1I2, RXRA, RXRB, RXRG, CYP1A1, CYP1A2, CYP1B1, CYP2B6, CYP3A4, CYP17A1 and CYP19A1) and risk of cryptorchidism (CO) and hypospadias (HS) in 334 Japanese (JPN) males (141 controls, 95 CO and 98 HS) and 187 Italian (ITA) males (129 controls and 58 CO). In the JPN study group, five SNPs from ARNT2 (rs2278705 and rs5000770), CYP1A2 (rs2069521), CYP17A1 (rs4919686) and NR1I2 (rs2472680) were significantly associated at both allelic and genotypic levels with risk of at least one genital malformation phenotype. In the ITA study group, two SNPs in AHR (rs3757824) and ARNT2 (rs1020397) were significantly associated with risk of CO. Interaction analysis of the positive SNPs using multifactor dimensionality reduction demonstrated that synergistic interaction between rs2472680, rs4919686 and rs5000770 had 62.81% prediction accuracy for CO (P ¼ 0.011) and that between rs2069521 and rs2278705 had 69.98% prediction accuracy for HS (P ¼ 0.001) in JPN population. In a combined analysis of JPN and ITA population, the most significant multi-locus association was observed between rs5000770 and rs3757824, which had 65.70% prediction accuracy for CO (P ¼ 0.055). Our findings indicate that genetic polymorphisms in genes involved in EED metabolism are associated with risk of CO and HS.

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Section: Discussionsupporting

confidence: 88%

Association of variants in genes involved in environmental chemical metabolism and risk of cryptorchidism and hypospadias

et al. 2012

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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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“…* Adjusted for age (20)(21)(22)(23)(24)(25)(26)(27)(28)(29)(30)(31)(32)(33)(34)(35)(36)(37)(38)(39)(40)(41)(42)(43)(44)(45)(46)(47)(48)(49), 50-64 and 65-85 years), race and ethnicity (Mexican American, other Hispanic, non-Hispanic White, non-Hispanic Black, other), education (less than 9th grade, 9-11th grade, high school/GED), cotinine level (,0·01 (LOD), 0·01-10 and .10 ng/ml), hepatitis B (positive serum hepatitis B surface antigen and core antibody, negative) and hepatitis C (positive serum hepatitis C antibody, negative), fibre intake (gm).…”

Section: Discussionmentioning

confidence: 99%

Urinary enterolactone associated with liver enzyme levels in US adults: National Health and Nutrition Examination Survey (NHANES)

Liu

Zhang

et al. 2015

Br J Nutr

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Phyto-oestrogens are a family of plant-derived xeno-oestrogens that appear to have beneficial effects on human health. To date, no data are available about phyto-oestrogen consumption affecting liver health in a population. The present study aimed to explore the relationship of urinary phyto-oestrogen metabolites with serum liver enzymes in US adults. A nationally representative sample of US adults in the National Health and Nutrition Examination Survey (NHANES) 2003 -10 was analysed. The cross-sectional study sample consisted of 6438 adults with data on urinary phyto-oestrogen levels, serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP) and g-glutamyl transaminase (GGT) concentrations and data on other potential confounders. Multivariate logistic regression and linear regression were applied to assess associations between urinary phyto-oestrogen levels and ALT, AST, ALP and GGT concentrations. We found a remarkable association between urinary enterolactone and GGT in both adult males (OR 0·37, 95 % CI 0·22, 0·61; P¼ 0·003) and females (OR 0·37, 95 % CI 0·26, 0·54; P¼ 0·009). Moreover, elevated enterolactone levels were inversely associated with ALT and AST levels in adult males. However, no association was present between levels of urinary daidzein, O-desmethylangolensin, equol, enterodiol or genistein with liver enzyme levels in this population. The present study results provide epidemiological evidence that urinary enterolactone levels are associated with liver GGT levels in humans. This suggests a potential protective effect of enterolactone on human liver function. However, the underlying mechanisms still need further investigation.

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Phytoestrogen Exposure Is Associated with Circulating Sex Hormone Levels in Postmenopausal Women and Interact withESR1andNR1I2Gene Variants

Cited by 55 publications

References 58 publications

Association of variants in genes involved in environmental chemical metabolism and risk of cryptorchidism and hypospadias

Association of variants in genes involved in environmental chemical metabolism and risk of cryptorchidism and hypospadias

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

Urinary enterolactone associated with liver enzyme levels in US adults: National Health and Nutrition Examination Survey (NHANES)

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