Dietary intakes of total and specific lignans are associated with clinical breast tumor characteristics

Dietary lignans may affect breast cancer by modifying tumor characteristics likely to affect prognosis. We investigated usual dietary intakes of total and specific lignans with tumor characteristics in 683 women with breast cancer and 611 healthy women without breast cancer enrolled in the Data Bank and BioRepository at Roswell Park Cancer Institute (RPCI). Clinicopathologic data were abstracted from the RPCI breast cancer database. Dietary lignan intakes were calculated from FFQ. OR and 95% CI were estimated with logistic regression adjusting for potential confounders and stratified by menopausal status. Women in the highest compared to the lowest tertile of total lignan intakes had a 40-50% lower odds of breast cancer regardless of menopausal status and substantially reduced odds of an invasive tumor, especially among premenopausal women [OR 0.48 (95% CI 0.26-0.86)]. Lignan intakes were inversely associated with odds of grade 3 tumors among premenopausal women. Lignan intakes were inversely associated with risk of estrogen receptor (ER) negative (ER(-)) breast cancer among premenopausal women [OR 0.16 (95% CI 0.03-0.44)] and particularly triple negative tumors [ER(-), progesterone receptor negative, HER2 negative; OR 0.16 (95% CI 0.04-0.62)]. There were significant differences in the contribution to these effects by specific lignans, especially matairesinol and lariciresinol. In summary, in this case-control study of dietary lignan intakes and breast cancer, we found that higher lignan intakes were associated with lower risks of breast cancer with more favorable prognostic characteristics. Future investigations are warranted to explore the strong associations observed with ER(-) cancer in premenopausal women.     

CYP17 genotype modifies the association between lignan supply and premenopausal breast cancer risk in humans

Cytochrome P450c17alpha (CYP17) has been associated with alterations in steroid hormone levels and premenopausal breast cancer risk and could modify the association between phytoestrogen intake and breast cancer risk. We examined plasma concentrations of enterolactone and genistein, estimated dietary phytoestrogen intake, CYP17 5'-UTR MspA1 genetic polymorphism, and breast cancer risk in 267 premenopausal breast cancer patients and 573 age-matched population controls from Germany. Multivariate logistic regression was used to estimate breast cancer risk associated with quartiles of phytoestrogen intake by genotype and to investigate gene-nutrient interactions. Premenopausal breast cancer risk was not significantly associated with the CYP17 A2 genotype. We observed a significant modifying effect of CYP17 genotype on plasma enterolactone-associated breast cancer risk (P for interaction < 0.01). Plasma enterolactone was significantly inversely related to breast cancer risk only in A2A2 carriers, showing odds ratios and 95% CI of 0.02 (0.00-0.41) and 0.01 (0.00-0.21) for the third and fourth quartiles vs. the lowest quartile, respectively. This inverse association was also found for the calculated enterolignan production as well as matairesinol intake. Compared with A1A1 carriers with the lowest enterolactone supply, the risk reduction associated with a high enterolactone supply resulted in a comparably decreased breast cancer risk for all genotypes. For genistein, no clear indication for a differential effect by CYP17 genotype was obtained. Our results suggest that CYP17 genotype modifies the protective effect of lignans on premenopausal breast cancer risk. Women homozygous for A2 allele benefit most from high plasma enterolactone concentrations and a high consumption of dietary precursors.     

Reports: plasma and dietary phytoestrogens and risk of premalignant lesions of the cervix

A number of epidemiological studies have observed an inverse association between phytoestrogens and risk of certain hormonally dependent cancers. We undertook an exploratory analysis of the relationship between specific phytoestrogens and premalignant cervical lesions. A case-control study of 122 women with histologically confirmed cervical squamous intraepithelial lesions (SILs) of the cervix and 183 cytologically normal controls was conducted from 1992 to 1996 in Honolulu, Hawaii. A cervical cell sample was obtained for human papillomavirus (HPV) testing. Dietary information was collected using a structured survey, and a fasting blood sample was taken for measurement of five isoflavonoids (genistein, glycitein, daidzein, O-desmethylangolensin, and equol), two flavonoids (hesperetin and naringenin), and two lignans (enterodiol and enterolactone). Plasma levels of equol and enterodiol were positively associated with cervical SIL risk: odds ratio, OR = 6.5; 95% confidence interval, CI = 1.4-29.2; P for trend = 0.02 and OR = 2.7; 95% CI = 1.1-6.3; P for trend = 0.01, respectively, for the highest relative to the lowest quartile level after adjustment for age, race/ethnicity, HPV infection, cigarette smoking, alcohol drinking, and lifetime number of sexual partners. A nonsignificant positive association with cervical SIL risk was observed for plasma enterolactone. Consistent with the relationships observed for the plasma lignans, dietary sources of lignans, including garlic and taro leaves/ong choy/marunggay, were positively associated with cervical SIL risk. A positive association was also suggested for other lignan sources such as seaweed, onions, grapefruit, and seeds. This is the first study to observe a positive association between specific phytoestrogens and premalignancies of the cervix. The results of this investigation should be considered preliminary and need to be verified in larger, prospective studies.     

The association between dietary lignans, phytoestrogen-rich foods, and fiber intake and postmenopausal breast cancer risk: a German case-control study

Phytoestrogens are structurally similar to estrogens and may affect breast cancer risk by mimicking estrogenic/antiestrogenic properties. In Western societies, whole grains and possibly soy foods are rich sources of phytoestrogens. A population-based case-control study in German postmenopausal women was used to evaluate the association of phytoestrogen-rich foods and dietary lignans with breast cancer risk. Dietary data were collected from 2,884 cases and 5,509 controls using a validated food-frequency questionnaire, which included additional questions phytoestrogen-rich foods. Associations were assessed using conditional logistic regression. All analyses were adjusted for relevant risk and confounding factors. Polytomous logistic regression analysis was performed to evaluate the associations by estrogen receptor (ER) status. High and low consumption of soybeans as well as of sunflower and pumpkin seeds were associated with significantly reduced breast cancer risk compared to no consumption (OR = 0.83, 95% CI = 0.70-0.97; and OR = 0.66, 95% CI = 0.77-0.97, respectively). The observed associations were not differential by ER status. No statistically significant associations were found for dietary intake of plant lignans, fiber, or the calculated enterolignans. Our results provide evidence for a reduced postmenopausal breast cancer risk associated with increased consumption of sunflower and pumpkin seeds and soybeans.     

Serum polychlorinated biphenyls, cytochrome P-450 1A1 polymorphisms, and risk of breast cancer in Connecticut women

Recent epidemiologic studies have suggested that genetic polymorphisms in the cytochrome P-450 1A1 gene (CYP1A1) may affect the relation between environmental exposure to polychlorinated biphenyls (PCBs) and breast cancer risk. The authors report results from a case-control study evaluating the potential effect of gene-environment interaction between CYP1A1 and serum PCB levels on breast cancer risk among Caucasian women in Connecticut. The study included 374 case women with histologically confirmed breast cancer and 406 noncancerous controls with information on both serum PCB level and CYP1A1 genotype (1999-2002). Compared with women who had the homozygous wild-type CYP1A1 m2 genotype, significantly increased risks of breast cancer were found for women with the CYP1A1 m2 variant genotype (odds ratio (OR) = 2.1, 95% confidence interval (CI): 1.1, 3.9), especially postmenopausal women (OR = 2.4, 95% CI: 1.1, 5.0). Risks associated with the CYP1A1 m2 variant genotype were highest for all women (OR = 3.6, 95% CI: 1.5, 8.2) and postmenopausal women (OR = 4.3, 95% CI: 1.6, 12.0) with higher serum PCB levels (611-2,600 ng/g). The CYP1A1 m1 and m4 genotypes were not associated with breast cancer risk independently or in combination with PCB exposure. In summary, the CYP1A1 m2 genetic polymorphism was associated with increased risk of female breast cancer and may modify the relation between PCB exposure and breast cancer risk.     

Intake of Energy-Dense Foods,Fast Foods,Sugary Drinks,and Breast Cancer Risk in African American and European American Women

Limiting energy-dense foods, fast foods, and sugary drinks that promote weight gain is a cancer prevention recommendation, but no studies have evaluated intake in relation to breast cancer risk in African American (AA) women. In a case-control study with 1692 AA women (803 cases and 889 controls) and 1456 European American (EA) women (755 cases and 701 controls), odds ratios (OR) and 95% confidence intervals (CI) for risk were computed, stratifying for menopausal and estrogen receptor (ER) status. Among postmenopausal EA women, breast cancer risk was associated with frequent consumption of energy-dense foods (OR = 2.95; 95% CI: 1.66–5.22), fast foods (OR = 2.35; 95% CI: 1.38–4.00), and sugary drinks (OR = 2.05; 95% CI: 1.13–3.70). Elevated risk of ER+ tumors in EA women was associated with energy-dense (OR = 1.75; 95% CI: 1.14–2.69) and fast foods (OR = 1.84; 95% CI: 1.22–2.77). Among AA women, frequent fast food consumption was related to premenopausal breast cancer risk (OR = 1.97; 95% CI: 1.13–3.43), and with ER+ tumors. Energy adjustment attenuated risk estimates in AA women, while strengthening them among EA women. Frequent consumption of energy-dense and fast foods that have poor nutritive value appeared to increase breast cancer risk in AA and EA women, with differences by menopausal status and ER status.     

Enterolactone and breast cancer: methodological issues may contribute to conflicting results in observational studies

Lignans found in plant foods are converted by the intestinal microflora to enterolignans. The structure of enterolignans is similar to that of estrogens, which has inspired researchers to examine a potential protective association in relation to health outcomes. Numerous epidemiological studies have measured concentration of enterolignans, mainly enterolactone, in blood or urine as a biomarker of lignan exposure and studied its relation to breast cancer risk. Case-control studies have shown decreased breast cancer risk associated with high circulating enterolactone concentrations, but results demonstrated by prospective cohort studies are less clear. The purpose of this review is to discuss factors that may contribute to these contradictory findings obtained in epidemiological studies, including age distribution, enterolactone measurement error, heterogeneity of breast cancer subtypes, and genetic factors. Different sources of enterolactone precursors may also contribute to inconclusive results. In conclusion, to get robust evidence of the health effects of lignans and enterolactone, more effort has to be put on methodological problems, including reducing measurement errors in enterolactone estimation, and to identify factors that modify the effect.     

血清有机氯农药DDT暴露、CYP1A1基因多态性与乳腺癌患病风险的病例对照研究

目的研究有机氯农药二氯二苯三氯乙烷(DDT)类物质暴露及细胞色素P4501A1m2突变基因型对女性乳腺癌患病风险的交互作用。方法运用病例对照研究方法,自2003年12月起至2004年9月止,收集组织病理学确诊乳腺癌的女性病例104例,社区来源的健康女性对照154名。采用问卷调查方法获取病例和对照乳腺癌相关危险因素的信息;用气相色谱-电子捕获(GC-ECD)方法检测血清样品中对,对-二氯二苯三氯乙烷(p,p’-DDT)、对,对-二氯二苯三氯乙烯(p,p’-DDE)的含量;用特异性聚合酶链反应(AS-PCR)法检测CYP1A1m2突变型基因;用logistic回归模型分析DDT类有机氯物质血清含量及CYP1A1m2突变基因型与乳腺癌患病风险的相对危险度(OR),以及二者的联合作用。结果病例和对照两组血清中的DDT的含量分别是(36.90±79.41)ng/ml和(50.60±150.70)ng/ml;DDE的含量分别是(7.43±11.10)ng/ml和(8.96±11.30)ng/ml,几何均数检验,两组间差异无统计学意义(P>0.05);CYP1A1m2型突变纯合型基因型(Val/Val)的调整OR=2.61,95%CI:1.00~6.80;绝经前乳腺癌病例与对照组中,携带Val突变基因型且DDT高暴露的OR=4.35,95%CI:1.140~16.950,参照等级是Ile/Ile野生纯合型基因且DDT低暴露。结论CYP1A1m2突变型基因型可能与乳腺癌有关,DDT暴露可能增加携带CYP1A1易感基因型的绝经前女性患乳腺癌的风险。     

Lignan and isoflavone excretion in relation to uterine fibroids: a case-control study of young to middle-aged women in the United States

BACKGROUND: Uterine fibroids are hormonally responsive; estradiol and progesterone stimulate their growth, and gonadotrophin-releasing hormone agonists shrink them. Phytoestrogens, including isoflavones and lignans, can act as weak estrogens or antiestrogens. OBJECTIVE: The objective of this case-control study was to evaluate the relation between uterine fibroid risk and phytoestrogen exposure. DESIGN: Two overnight urine collections (48 h apart) from 170 uterine fibroid cases and 173 controls were analyzed for isoflavonoids (ie, daidzein, genistein, equol, and O-desmethylangolensin) and lignans (enterodiol and enterolactone). Logistic regression was used to determine associations between the mean excretion of the 2 collections and the risk of uterine fibroids. RESULTS: Unadjusted isoflavone excretion did not differ significantly between cases and controls (2.33 +/- 5.82 and 2.60 +/- 5.90 nmol/mg Cr, respectively; P = 0.68), but cases excreted significantly less lignans than did controls (2.86 +/- 3.45 and 4.57 +/- 6.67 nmol/mg Cr, respectively; P < 0.01). The trend for a reduced risk of uterine fibroids with increasing quartiles of lignan excretion was significant (odds ratio for highest versus lowest quartile = 0.31; 95% CI: 0.17, 0.58; P for trend < 0.01). When adjusted for age, BMI, race, family history of uterine fibroids, and isoflavone excretion, this trend remained but was attenuated (P = 0.07). CONCLUSIONS: Our findings suggest a modest inverse association between lignan excretion and uterine fibroid risk. Whether this relation represents an effect of lignans per se or of other constituents of lignan-containing foods on the development of uterine fibroids remains to be determined. No association was found between isoflavone excretion and uterine fibroids; however, the intake of soy foods, the primary source of isoflavones, was low in this population.     

Cruciferous vegetables, the GSTP1 Ile105Val genetic polymorphism, and breast cancer risk

BACKGROUND: Cruciferous vegetables are the primary source of isothiocyanates and other glucosinolate derivatives that are known to induce phase II detoxifying enzymes, including glutathione S-transferases (GSTs). OBJECTIVE: We investigated the independent and combined effects of cruciferous vegetable intake and the GSTP1 Ile(105)Val genetic polymorphism on breast cancer risk. DESIGN: Analyses included 3035 cases and 3037 population controls who were participating in the Shanghai Breast Cancer Study and for whom diet and genetic data were complete (87% of cases and 85% of controls). RESULTS: With the use of multivariate logistic regression, the GSTP1 Val/Val genotype was significantly associated with greater breast cancer risk (OR = 1.50; 95% CI: 1.12, 1.99). The association was significantly greater in premenopausal women (OR = 1.69; 95% CI: 1.17, 2.43) than in postmenopausal women (OR = 1.20; 95% CI: 0.74, 1.92). Total cruciferous vegetable intake was not significantly associated with breast cancer risk, although subjects reporting greater turnip (P for trend < 0.001) and Chinese cabbage (P for trend = 0.049) intakes had a significantly lower postmenopausal breast cancer risk. Women with the GSTP1 Val/Val genotype and low cruciferous vegetable intake had a breast cancer risk 1.74-fold (95% CI: 1.13, 2.67) that of women with the Ile/Ile or Ile/Val genotype. This effect of low cruciferous vegetable intake and the Val/Val genotype was seen predominantly among premenopausal women (OR = 2.08; 95% CI = 1.20, 3.59). CONCLUSIONS: Cruciferous vegetable intake consistent with high isothiocyanate exposure may reduce breast cancer risk. Cruciferous vegetable intake also may ameliorate the effects of the GSTP1 genotype.     

Sesamin is one of the major precursors of mammalian lignans in sesame seed (Sesamum indicum) as observed in vitro and in rats

Plant lignans occur in many foods, with flaxseed presently recognized as the richest source. Some plant lignans can be converted by intestinal microbiota to the mammalian lignans, enterodiol and enterolactone, which may have protective effects against hormone-related diseases such as breast cancer. This study determined whether plant lignans in sesame seed, particularly sesamin, could be metabolized to the mammalian lignans. The total plant lignan concentration in sesame seed (2180 micromol/100 g) was higher than that in flaxseed (820 micromol/100 g). In vitro fermentation with human fecal inoculum showed conversion of sesamin to the mammalian lignans, although at a lower rate (1.1%) compared with that of secoisolariciresinol diglucoside (57.2%). However, when fed to female Sprague-Dawley rats for 10 d, sesamin (15 mg/kg body weight) and a 10% sesame seed diet resulted in greater (P < 0.05) urinary mammalian lignan excretion (3.2 and 11.2 micromol/d, respectively), than the control (< 0.05 micromol/d). We conclude that sesame seed is a rich source of mammalian lignan precursors and sesamin is one of them. From intermediate metabolites of sesamin identified in rat urine by GC-MS, a tentative metabolic pathway of sesamin to mammalian lignans is suggested.     

Dietary flavonoid intake and breast cancer risk among women on Long Island

Flavonoids are found in a variety of foods and have anticarcinogenic properties in experimental models. Few epidemiologic studies have examined whether flavonoid intake is associated with breast cancer in humans. In this study, the authors investigated whether dietary flavonoid intake was associated with reduced risk of breast cancer in a population-based sample of US women. They conducted a case-control study among women who resided in Nassau and Suffolk counties on Long Island, New York. Cases and controls were interviewed about known and suspected risk factors and asked to complete a food frequency questionnaire regarding their average intake in the prior 12 months. A total of 1,434 breast cancer cases and 1,440 controls provided adequate responses. A decrease in breast cancer risk was associated with flavonoid intake; the decrease was most pronounced among postmenopausal women for flavonols (odds ratio (OR) = 0.54, 95% confidence interval (CI): 0.40, 0.73), flavones (OR = 0.61, 95% CI: 0.45, 0.83), flavan-3-ols (OR = 0.74, 95% CI: 0.55, 0.99), and lignans (OR = 0.69, 95% CI: 0.51, 0.94). The authors conclude that intake of flavonols, flavones, flavan-3-ols, and lignans is associated with reduced risk of incident postmenopausal breast cancer among Long Island women. These results suggest that US women can consume sufficient levels of flavonoids to benefit from their potential chemopreventive effects.     

Body size and breast cancer risk in black women and white women: the Carolina Breast Cancer Study

The relation between body size and breast cancer risk was investigated in a population-based, case-control study of Black women (350 cases, 353 controls) and White women (523 cases, 471 controls) from North Carolina, aged 20-74 years in 1993-1996. Logistic regression analyses compared tertiles of each body size variable, adjusting for age and breast cancer risk factors (results shown for highest relative to lowest tertile). Among premenopausal women, body mass index (kg/m2) was inversely associated with breast cancer (odds ratio (OR) = 0.46, 95% confidence interval (CI): 0.26, 0.80) for Whites but not for Blacks. There was essentially no association among postmenopausal women. Higher waist/hip ratio, adjusted for body mass index, increased risk for all women. Odds ratios for Black and White premenopausal women were 2.50 (95% CI: 1.10, 5.67) and 2.44 (95% CI: 1.17, 5.09), respectively; odds ratios for Black and White postmenopausal women were 1.62 (95% CI: 0.70, 3.79) and 1.64 (95% CI: 0.88, 3.07), respectively. Findings for body mass index differed among Black women when stratified by age (<50 years) (OR = 0.50, 95% CI: 0.25, 1.01) instead of menopausal status. Thus, the associations of breast cancer with body mass index and waist/hip ratio among Black women are similar to those documented for Whites, despite different body size profiles on average.     

Fruits, vegetables, soy foods and breast cancer in pre- and postmenopausal Korean women: a case-control study

We carried out a case-control study to examine the relationship between fruits, vegetables, and soy foods intake with breast cancer risk in Korean women. Incident cases (n = 359) were identified through cancer biopsies and hospital-based controls (n = 708) were selected in the same hospitals. Subjects were asked to indicate usual dietary habits, which were assessed using a semi-quantitative food frequency questionnaire (98 items). Odds ratio (OR) and 95% confidence intervals (95% CI) were calculated by unconditional logistic regression after adjustment for additional confounding factors according to the menopausal status. High grape intake showed an inverse association of breast cancer in postmenopausal women (OR = 0.59, 95% CI = 0.35-0.95; p for trend = 0.05). High tomato intake was associated with reduced breast cancer risk in premenopausal women (OR = 0.59, 95% CI = 0.38-0.89, p for trend = 0.04). In postmenopausal women, green pepper intake showed an inverse association of breast cancer risk (OR = 0.60, 95% CI = 0.43-0.96, p for trend = 0.03). High soybean intake showed an inverse association of breast cancer in postmenopausal women (OR = 0.61, 95% CI = 0.34-0.89, p for trend = 0.02). Our study suggests that high intake of some fruits, vegetables, and soybeans may be associated with a reduced breast cancer risk.     

Phyto-oestrogens and risk of prostate cancer in Scottish men

A population-based case-control study of diet, inherited susceptibility and prostate cancer was undertaken in the lowlands and central belt of Scotland to investigate the effect of phyto-oestrogen intake and serum concentrations on prostate cancer risk. A total of 433 cases and 483 controls aged 50-74 years were asked to complete a validated FFQ and provide a non-fasting blood sample. Multivariate logistic regression analysis found significant inverse associations with increased serum concentrations of enterolactone (adjusted OR 0.40, 95 % CI 0.22, 0.71] and with the consumption of soy foods (adjusted OR 0.52, 95 % CI 0.30, 0.91). However, no significant associations were observed for isoflavone intake or serum genistein, daidzein and equol. This study supports the hypotheses that soy foods and enterolactone metabolised from dietary lignans protect against prostate cancer in older Scottish men.     

Evaluation of Breast Cancer Risk in a Multigenic Model Including Low Penetrance Genes Involved in Xenobiotic and Estrogen Metabolisms

Breast cancer has become the most frequent cancer among women in Westernized countries. The majority of breast cancers are due to low penetrance genes, which can act with environmental factors, particularly nutrition. Polymorphisms in gene coding for xenobiotic and estrogen metabolic pathways could increase individual cancer susceptibility and lead to the indication of individuals at higher cancer risk. A population-based, case-control study consisting of 911 breast cancer cases and 1,000 healthy control cases was performed. The association between 11 single nucleotide polymorphisms (SNP) in 7 genes and breast cancer risk was investigated in a multigenic model. The CYP1B1-432 Leu-Val and Val-Val genotypes significantly increased risk [odds ratio (OR) = 1.23, 95% confidence interval (CI) = 1.08–1.39; OR = 1.51, 95% CI = 1.17–1.94, respectively] similarly as observed with CYP1B1-453 (Asn-Ser genotype: OR = 1.17, 95% CI = 1.00–1.37; Ser-Ser genotype: OR = 1.38, 95% CI = 1.00–1.89). We showed that catechol-O-methyltransferase (COMT) could modulate the risk conferred by CYP1B1, ESR, GSTP1, and NAT2 acetylation phenotype. Additionally, a higher risk conferred by the variant for COMT was noted only for individuals presenting a high waist-to-hip ratio (COMT Val-Met, OR = 1.60, 95% CI = 1.04–2.44; COMT Met-Met, OR = 1.57, 95% CI = 0.98–2.53), suggesting a relationship with abdominal adiposity. In conclusion, COMT constitutes a crucial element in estrogen metabolism by regulating carcinogen metabolites elimination and, consequently, is a major factor in breast cancer risk.     

Dietary intake of soy protein and tofu in association with breast cancer risk based on a case-control study

Soy food and its constituents may protect against breast cancer, but the association between soy intake and decreased breast cancer risk is inconsistent. We evaluated the relationship between breast cancer risk and the dietary intake of soy protein as measured by total soy food and tofu intake. Histologically confirmed cases (n = 362) were matched to controls by age (within 2 yr) and menopausal status. High soy protein intake was associated with reduced breast cancer risk in analyses adjusted for potential confounders including dietary factors among premenopausal women (odds ratio [OR] = 0.39 in the highest quintile, 95% confidence interval [CI] = 0.22-0.93, P for trend = 0.03) and postmenopausal women (OR = 0.22, 95% CI = 0.06-0.88, P for trend = 0.16). We also found an inverse association between total tofu intake and breast cancer risk among premenopausal women (for total tofu intake, OR = 0.23 in the highest quintile, 95% CI = 0.11-0.48, P for trend < 0.01; for at least 1 serving of tofu as the main ingredient per day, OR = 0.26, 95% CI = 0.13-0.55, P for trend < 0.01). We concluded that increased regular soy food intake at a level equivalent to traditional Korean consumption levels may be associated with a reduced risk of breast cancer, and this effect is more pronounced in premenopausal women.     

Inverse association between dietary and serum conjugated linoleic acid and risk of breast cancer in postmenopausal women

Conjugated linoleic acid (CLA) is anticarcinogenic in experimental animal studies. We studied dietary and serum CLA in Finnish patients with breast cancer in 1992-1995. Participants were consecutive women with breast cancer (68 premenopausal and 127 postmenopausal) and population-based control women (75 premenopausal and 133 postmenopausal), matched for age and area of residence. Diet was assessed by a validated food frequency questionnaire and the fatty acid composition of serum by gas-liquid chromatography. In postmenopausal women, dietary CLA, serum CLA, myristic acid, and trans-vaccenic acid were significantly lower in cases than in controls. The odds ratio for breast cancer in the highest quintile vs. the lowest was 0.4 [95% confidence interval (CI) = 0.2-0.9]for CLA, 0.3 (95% CI = 0.1-0.7) for myristic acid, and 0.3 (95% CI = 0.1-0.7) for trans-vaccenic acid in serum. The odds ratios remained similar after adjustment for known risk factors of breast cancer. A diet composed of CLA-rich foods, particularly cheese, may protect against breast cancer in postmenopausal women, but it is impossible to assess the independent effects of CLA in this study. The findings may be of relevance for food production, inasmuch as it is possible to increase CLA and its precursor trans-vaccenic acid in foods by modifying the feeding of ruminants.     

Plasma enterolignan concentrations and colorectal cancer risk in a nested case-control study

Enterolignans are biphenolic compounds that possess several biologic activities whereby they may influence carcinogenesis. The authors investigated the association between plasma enterolactone and enterodiol and colorectal cancer risk in a Dutch prospective study. Among more than 35,000 participants aged 20-59 years, 160 colorectal cancer cases were diagnosed after 7.5 years of follow-up (1987-2003). Cohort members who were frequency-matched to the cases on age, sex, and study center were selected as controls (n = 387). Plasma enterodiol and enterolactone were not associated with risk of colorectal cancer after adjustment for known colorectal cancer risk factors (highest quartile vs. lowest: for enterodiol, odds ratio = 1.11, 95% confidence interval: 0.56, 2.20 (p-trend = 0.75); for enterolactone, odds ratio = 1.70, 95% confidence interval: 0.88, 3.27 (p-trend = 0.15)). However, sex (p-interaction = 0.06) and body mass index (p-interaction < 0.01) modified the relation between plasma enterolactone and colorectal cancer risk; increased risks were observed among women and subjects with a high body mass index. The association between plasma enterodiol and colorectal cancer risk was modified by smoking status; risk was increased among current smokers (p-interaction < 0.01). These findings do not support the hypothesis that high plasma enterodiol or enterolactone concentrations are associated with reduced risk of colorectal cancer.     

Estrogen metabolism and risk of breast cancer: a prospective study of the 2:16alpha-hydroxyestrone ratio in premenopausal and postmenopausal women

Experimental and clinical evidence suggests that 16alpha-hydroxylated estrogen metabolites, biologically strong estrogens, are associated with breast cancer risk, while 2-hydroxylated metabolites, with lower estrogenic activity, are weakly related to this disease. This study analyzes the association of breast cancer risk with estrogen metabolism, expressed as the ratio of 2-hydroxyestrone to 16alpha-hydroxyestrone, in a prospective nested case-control study. Between 1987 and 1992, 10,786 women (ages 35-69 years) were recruited to a prospective study on breast cancer in Italy, the "Hormones and Diet in the Etiology of Breast Cancer" (ORDET) study. Women with a history of cancer and women on hormone therapy were excluded at baseline. At recruitment, overnight urine was collected from all participants and stored at -80 degrees C. After an average of 5.5 years of follow-up, 144 breast cancer cases and four matched controls for each case were identified among the participants of the cohort. Among premenopausal women, a higher ratio of 2-hydroxyestrone to 16alpha-hydroxyestrone at baseline was associated with a reduced risk of breast cancer: women in the highest quintile of the ratio had an adjusted odds ratio (OR) for breast cancer of 0.58 [95% confidence interval (CI) = 0.25-1.34]. The corresponding adjusted OR in postmenopausal women was 1.29 (95% CI = 0.53-3.10). Results of this prospective study support the hypothesis that the estrogen metabolism pathway favoring 2-hydroxylation over 16alpha-hydroxylation is associated with a reduced risk of invasive breast cancer risk in premenopausal women.