Urinary polyphenols, glutathione S-transferases copy number variation, and breast cancer risk: results from the Shanghai women's health study

In vitro studies have found that flavanol epigallocatechin (EGC) and flavonols, but not flavanol epicatechin (EC), activate glutathione S-transferases (GSTs), a family of phase II enzymes that detoxify reactive oxygen species, such as catechol estrogen metabolites. This study was designed to investigate prospectively whether urinary excretion of tea polyphenols interacts with GST polymorphisms to influence breast cancer risk. We conducted a study of 352 incident breast cancer cases and 701 individually matched controls nested within the Shanghai Women's Health Study cohort of women aged 40-70 yr at baseline. Liquid chromatography tandem mass spectrometry was used to measure urinary excretion of flavanols and flavonols. Real-time multiplex PCR was used to quantify the copy number variation in the GSTM1 and GSTT1 genes. Urinary excretion of flavonols and flavanols, particularly EGC (P = 0.02), was significantly higher among women null for GSTM1 than those positive for GSTM1. Flavonols and flavanols (EGC in particular) were associated with a reduced risk of breast cancer among those null for GSTM1 and GSTT1, with a P-value of 0.04 for the interaction between EGC and GSTM1 polymorphism. In contrast, among women possessing both GSTM1 and GSTT1, breast cancer risk increased with levels of flavonols, particularly kaempferol. The differential associations between polyphenols and breast cancer risk by GST polymorphisms, if confirmed, may provide a new avenue for the personalized prevention of breast cancer.     

Urinary biomarkers of tea polyphenols and risk of colorectal cancer in the Shanghai Cohort Study

There have been no studies on specific tea polyphenol biomarkers and risk of colorectal cancer in humans. We prospectively examined the associations between validated biomarkers of specific tea polyphenols and risk of developing colorectal cancer among a cohort of 18,244 men in Shanghai, China, with 16 years of follow-up. Epigallocatechin (EGC), 4'-O-methyl-epigallocatechin (4'-MeEGC) and epicatechin, and their metabolites in baseline urine samples were measured on 162 incident colorectal cancer cases and 806 matched controls. Individuals with high prediagnostic urinary EGC levels had a lower risk of colon cancer. Compared with undetectable EGC, odds ratios (95% confidence interval) for colon cancer in the lowest, intermediate and highest tertile of detectable EGC were 0.64 (0.33-1.24), 0.60 (0.30-1.20) and 0.40 (0.19-0.83), respectively (p for trend = 0.02). A similar inverse relation between 4'-MeEGC and colon cancer also was observed. Compared with the lowest quartile, odds ratios (95% confidence intervals) for colon cancer in the 2nd, 3rd and 4th quartiles of urinary 4'-MeEGC were 0.49 (0.25-0.96), 0.32 (0.16-0.67) and 0.41 (0.20-0.84), respectively (p for trend = 0.006). The strongest protective effect was seen for regular tea drinkers who showed high levels of urinary EGC and 4'-MeEGC. No association between urinary levels of epicatechin or its metabolite and colon cancer risk was observed. Urinary levels of tea polyphenols and their metabolites were not associated with rectal cancer risk. The present study supports the notion of tea catechins as chemopreventive agents against the development of colon cancer in humans.     

Urinary tea polyphenols in relation to gastric and esophageal cancers: a prospective study of men in Shanghai,China

Experimental studies have shown that tea and tea polyphenols have anticarcinogenic properties. There have been no prospective investigations examining the relationship between tea polyphenols and cancer risk using validated biomarkers. In the present study, a nested case-control study design was used to investigate the association between prediagnostic urinary tea polyphenol markers and subsequent risk of gastric and esophageal cancers. One hundred and ninety incident cases of gastric cancer and 42 cases of esophageal cancer occurring in members of the Shanghai Cohort (18 244 men aged 45-64 years at recruitment with up to 12 years of follow-up) were compared with 772 cohort control subjects. The control subjects were individually matched to the index cases by age, month and year of sample collection, and neighborhood of residence (case-control ratio = 1:3 for gastric cancer, 1:5 for esophageal cancer). Urinary tea polyphenols, including epigallocatechin (EGC) and epicatechin (EC), and their respective metabolites 5-(3',4',5'-trihydroxyphenyl)-gamma-valerolactone (M4) and 5-(3',4'-dihydroxyphenyl)-gamma-valerolactone (M6), were measured in all study subjects by means of a validated assay. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated from logistic regression models. After exclusion of cases diagnosed under 4 years follow-up, urinary EGC positivity showed a statistically significant inverse association with gastric cancer (OR = 0.52, 95% CI = 0.28-0.97) after adjustment for Helicobactor pylori seropositivity, smoking, alcohol drinking, and level of serum carotenes. The protective effect was primarily seen among subjects with low (below population median) serum carotenes. The odds ratio for EGC positivity was 0.49 (95% CI = 0.26-0.94) among subjects with low serum carotenes while the corresponding odds ratio among subjects with higher levels of serum carotenes was 1.02 (95% CI = 0.46-2.28). Similar tea polyphenol-cancer risk associations were observed when the gastric cancer and esophageal cancer sites were combined. The present study provides direct evidence that tea polyphenols may act as chemopreventive agents against gastric and esophageal cancer development.     

Tea intake, COMT genotype, and breast cancer in Asian-American women

There is substantial in vitro and in vivo evidence implicating tea polyphenols as chemopreventive agents against various cancers. In a case-control study conducted among Asian-American women in Los Angeles County, we reported a significant inverse relationship between intake of green tea and risk of breast cancer (A. H. Wu et al., Int. J. Cancer, 106: 574-579, 2003). Because catechol-containing tea polyphenols are very rapidly O-methylated by human catechol-O-methyltransferase (COMT), we are interested in determining whether the association between tea intake and breast cancer differed in women according to COMT genotype. We examined the interrelationships between tea intake, COMT genotype, and breast cancer risk in 589 incident cases and 563 population-based controls from a population-based case-control study of breast cancer in Chinese-, Japanese-, and Filipino-American women in Los Angeles County. Risk of breast cancer was influenced significantly by intake of tea, particularly green tea intake. However, the inverse association between tea intake and breast cancer risk was observed only among individuals who possessed at least one low-activity COMT allele. Among women who carried at least one low activity COMT allele, tea drinkers showed a significantly reduced risk of breast cancer (adjusted odds ratio, 0.48; 95% confidence interval, 0.29-0.77) compared with nontea drinkers after adjustment for relevant demographic, menstrual, reproductive, and dietary factors. This risk reduction was observed in relation to both green tea and black tea intake. In contrast, risk of breast cancer did not differ between tea drinkers and nontea drinkers among those who were homozygous for the high activity COMT allele (adjusted odds ratio, 1.02; 95% confidence interval, 0.66-1.60). In conclusion, tea catechins appeared to reduce breast cancer risk in this study of Asian-American women. Reduction in risk was strongest among persons who had the low activity COMT alleles, suggesting these individuals were less efficient in eliminating tea catechins and may derive the most benefit from these compounds.     

Urinary bisphenol A-glucuronide and postmenopausal breast cancer in Poland

Purpose

Concerns regarding a possible link between bisphenol A (BPA) and breast cancer have been mounting, but studies in human populations are lacking. We evaluated the association between the major urinary BPA metabolite [BPA-glucuronide (BPA-G)] and postmenopausal breast cancer risk in a large population-based case–control study conducted in two cities in Poland (2000–2003); we further explored the association of BPA-G levels with known postmenopausal breast cancer risk factors in our control population.

Methods

We analyzed creatinine-adjusted urinary BPA-G levels among 575 postmenopausal cases matched on age and study site to 575 controls without breast cancer using a recently developed assay. Odds ratios and 95 % confidence intervals were used to estimate the association between urinary BPA-G level and breast cancer using conditional logistic regression. Among controls, geometric mean BPA-G levels were compared across categories of breast cancer risk factors using linear regression models.

Results

There was no indication that increased BPA-G was associated with postmenopausal breast cancer (p-trend = 0.59). Among controls, mean BPA-G was higher among women reporting extended use of menopausal hormones, a prior screening mammogram, and residence in Warsaw. Other comparisons across strata of postmenopausal breast cancer risk factors were not related to differences in BPA-G.

Conclusions

Urinary BPA-G, measured at the time of diagnosis, is not linked to postmenopausal breast cancer.     

Urinary androgens and breast cancer risk: results from a long-term prospective study based in Guernsey

Between 1961 and 1967 a cohort of over 5000 women volunteered for a prospective study to determine the relationship between the urinary androgen metabolites, androsterone (A) and aetiocholanolone (E), and risk of breast cancer. During the first 10 years of the study the concentration of urinary A and E was determined in 1887 of the urine specimens. In 1971 we reported that subnormal amounts of urinary A and E were associated with a significantly increased risk of breast cancer. The cohort has been followed regularly during the 37 years since inception of the study and, by May 1998, 248 women had been diagnosed with breast cancer. Urinary androgen metabolites had been measured in 116 of these cases. Analysis of these data confirmed that women diagnosed in the first decade of the study were more likely to have low levels of urinary androgen metabolites. In the following decades, however, those who developed breast cancer were more likely to have manifested an increased A and E excretion. The reversal in the relationship between androgen metabolite excretion and risk suggests that age, or probably more importantly, menopausal status at diagnosis is an important modifying factor. Dichotomizing at age 50 it was found that in the younger age group (predominantly premenopausal) the rate ratios in the lowest tertile of A or E excretion were two- to threefold greater than for those in the highest tertile (chi2(1) = 3.57; P = 0.06: chi2(1) = 4.70; P = 0.03 for A and E respectively). In contrast, in the older age group comprising predominantly post-menopausal women, the rate ratios associated with the lowest tertile of A or E were half that of those in the highest tertile (chi2(1) = 4.10; P = 0.04; chi2(1) = 8.72; P = 0.003 for A and E respectively). This suggests that there may be different endocrine promotional factors for pre-and post-menopausal breast cancer. Hormonal risk factors may vary during the lifetime of an individual woman and this may have profound consequences for prevention strategies.     

Urinary estrogens and estrogen metabolites and subsequent risk of breast cancer among premenopausal women

Endogenous estrogens and estrogen metabolism are hypothesized to be associated with premenopausal breast cancer risk but evidence is limited. We examined 15 urinary estrogens/estrogen metabolites and breast cancer risk among premenopausal women in a case-control study nested within the Nurses' Health Study II (NHSII). From 1996 to 1999, urine was collected from 18,521 women during the mid-luteal menstrual phase. Breast cancer cases (N = 247) diagnosed between collection and June 2005 were matched to two controls each (N = 485). Urinary estrogen metabolites were measured by liquid chromatography-tandem mass spectrometry and adjusted for creatinine level. Relative risks (RR) and 95% confidence intervals (CI) were estimated by multivariate conditional logistic regression. Higher urinary estrone and estradiol levels were strongly significantly associated with lower risk (top vs. bottom quartile RR: estrone = 0.52; 95% CI, 0.30-0.88; estradiol = 0.51; 95% CI, 0.30-0.86). Generally inverse, although nonsignificant, patterns also were observed with 2- and 4-hydroxylation pathway estrogen metabolites. Inverse associations generally were not observed with 16-pathway estrogen metabolites and a significant positive association was observed with 17-epiestriol (top vs. bottom quartile RR = 1.74; 95% CI, 1.08-2.81; P(trend) = 0.01). In addition, there was a significant increased risk with higher 16-pathway/parent estrogen metabolite ratio (comparable RR = 1.61; 95% CI, 0.99-2.62; P(trend) = 0.04). Other pathway ratios were not significantly associated with risk except parent estrogen metabolites/non-parent estrogen metabolites (comparable RR = 0.58; 95% CI, 0.35-0.96; P(trend) = 0.03). These data suggest that most mid-luteal urinary estrogen metabolite concentrations are not positively associated with breast cancer risk among premenopausal women. The inverse associations with parent estrogen metabolites and the parent estrogen metabolite/non-parent estrogen metabolite ratio suggest that women with higher urinary excretion of parent estrogens are at lower risk.     

Dietary intakes of mushrooms and green tea combine to reduce the risk of breast cancer in Chinese women

To investigate effects of dietary mushrooms and joint effects of mushrooms and green tea on breast cancer, a case–control study was conducted in southeast China in 2004–2005. The incident cases were 1,009 female patients aged 20–87 years with histologically confirmed breast cancer. The 1,009 age‐matched controls were healthy women randomly recruited from outpatient breast clinics. Information on frequency and quantity of dietary intake of mushrooms and tea consumption, usual diet, and lifestyle were collected by face‐to‐face interview using a validated and reliable questionnaire. Compared with nonconsumers, the Odds ratios (Ors) were 0.36 (95% CI = 0.25–0.51) and 0.53 (0.38–0.73) for daily intake of ≥10 g fresh mushrooms and ≥4 g dried mushrooms, based on multivariate logistic regression analysis adjusting for established and potential confounders. There were dose–response relationships with significant tests for trend (p < 0.001). The inverse association was found in both pre‐ and postmenopausal women. Compared with those who consumed neither mushrooms nor green tea, the ORs were 0.11 (0.06–0.20) and 0.18 (0.11–0.29) for daily high intake of fresh and dried mushrooms combined with consuming beverages made from ≥1.05 g dried green tea leaves per day. The corresponding linear trends were statistically significant for joint effect (p < 0.001). We conclude that higher dietary intake of mushrooms decreased breast cancer risk in pre‐ and postmenopausal Chinese women and an additional decreased risk of breast cancer from joint effect of mushrooms and green tea was observed. More research is warranted to examine the effects of dietary mushrooms and mechanism of joint effects of phytochemicals on breast cancer. © 2008 Wiley‐Liss, Inc.     

CYP2A6 activity determined by caffeine phenotyping: association with colorectal cancer risk.

Cytochrome P450 2A6 (CYP2A6) catalyzes the metabolic activation of several procarcinogens including dietary and environmental nitrosamines, and the involvement of CYP2A6 in cancer development has been postulated. CYP2A6 phenotype was determined using caffeine as a probe drug in individuals participating in a case-control study of colorectal cancer (127 cases and 333 controls matched on age, gender, race, and geographic region). Conversion of the caffeine metabolite 1,7-dimethylxanthine (17X) to 1,7-dimethyl uric acid (17U) is catalyzed primarily by CYP2A6, and this activity can be assayed by comparison of urinary molar ratios of metabolites. Caffeine (200 mg) was administered to each participant, and a 4-5 h postadministration urine sample was collected. Urinary metabolites of caffeine were separated by high-performance liquid chromatography and quantified by comparison to authentic standards. We examined the distributions of the ratio, 17U:17X, according to subject characteristics among controls. In case-control comparisons, subjects in the medium and high tertiles of CYP2A6 activity had an increased risk of colorectal cancer compared with subjects with low activity. Odds ratios from a conditional logistic regression model for medium and high 17U:17X ratio were 2.0 (95% confidence interval, 1.1-3.7) and 2.6 (95% confidence interval, 1.5-4.5), respectively (P for trend = 0.001). CYP2A6 phenotype has not been compared previously between cancer cases and controls. We found a strong relationship between CYP2A6 activity, measured by urinary caffeine metabolite ratio, and colorectal cancer risk.     

Effects of a moderate intensity exercise intervention on estrogen metabolism in postmenopausal women.

Physical activity has been associated with reduced breast cancer risk, potentially via hormonal pathways, and high urinary excretion of 2-hydroxyestrone (2-OH E(1)) relative to 16alpha-hydroxyestrone (16alpha-OH E(1)) also has been associated with reduced breast cancer risk. Studies suggest that body composition and exercise can influence estrogen metabolism. We determined the effects of a 12-month moderate intensity aerobic exercise intervention on urinary 2-OH E(1), 16alpha-OH E(1), and their ratio in overweight and obese, previously sedentary, postmenopausal women, ages 50-75 years. Women were randomized to a 12-month exercise intervention (n = 87) or stretching control group (n = 86); 170 completed the study. Urinary 2- and 16alpha-OH E(1) were measured in spot urines collected at baseline, 3, and 12 months. Body composition was measured at baseline and 12 months. Differences between exercisers and controls for excretion of estrogen metabolites were determined using general estimating equations. Further analyses assessed change in estrogen metabolites and their ratio by subgroups of change in body composition. Overall, there were no significant effects of the exercise intervention on 2-OH E(1), 16alpha-OH E(1), or their ratio (P > 0.05). There appeared to be an effect of change in intra-abdominal fat and adherence to the exercise intervention on change in the estrogen metabolites or their ratio. However, this did not reflect a potentially desirable change in estrogen metabolites associated with the exercise intervention. Thus, this 12-month moderate intensity exercise intervention did not significantly alter urinary excretion of 2-OH E(1), 16alpha-OH E(1), or their ratio in this population of women.     

Urinary excretion of phytoestrogens and risk of breast cancer among Chinese women in Shanghai.

Although the majority of ecological and experimental studies have suggested a potential role of phytoestrogens in breast cancer prevention, findings from epidemiological studies have been inconsistent. Part of the inconsistencies may be attributable to the difficulty in measuring intake levels of phytoestrogens. Overnight urine samples from 250 incident breast cancer cases and their individually matched controls were analyzed for urinary excretion rates of isoflavonoids, mammalian lignans, and citrus flavonoids. The study subjects were a subset of the participants in the Shanghai Breast Cancer Study, a large population-based case-control study conducted in Shanghai from 1996-1998. To minimize potential influence of treatment on the exposure of interest, urine samples from breast cancer cases were collected before cancer therapy. Urinary excretion of total isoflavonoids and mammalian lignans was substantially lower in breast cancer cases than in controls. The median excretion rate of total isoflavonoids was 13.97 nmol/mg creatinine in cases and 23.09 in controls (P = 0.01), and the median excretion rate of total lignans was 1.77 in cases and 4.16 in controls (P < 0.01). The risk of breast cancer was reduced with increasing excretion of total isoflavonoids (P for trend, 0.04) and total lignans (P for trend, <0.01), with adjusted odds ratios of 0.62 (95% confidence interval, 0.39-0.99) and 0.40 (95% confidence interval, 0.24-0.64) observed for the highest versus the lowest tertile of total isoflavonoid and lignan excretion, respectively. The adjusted odds ratio was 0.28 (95% confidence interval, 0.15-0.50) for women who had a high excretion rate of both total lignans and isoflavonoids compared with those with a low excretion of both groups of phytoestrogens. No association was observed with citrus flavonoids. The results from this study suggest that high intake of certain phytoestrogens may reduce the risk of breast cancer.     

Tea and circulating estrogen levels in postmenopausal Chinese women in Singapore

The role of tea in the etiology of breast cancer is controversial. We recently provided the first set of human evidence that breast cancer risk is significantly inversely associated with tea intake, largely confined to intake of green tea. Since black tea and green tea possess comparable levels of the total tea polyphenols that possess antioxidative activities, reasons for the paradoxical effects of green tea and black tea on breast cancer protection are not apparent. Some limited evidence suggests that green tea may have downregulatory effects on circulating sex-steroid hormones, whereas black tea may have upregulatory effects. We therefore, investigated the relationship between tea intake, and plasma estrogen and androstenedione levels in a cross-sectional study of healthy postmenopausal Chinese women in Singapore. In this group of 130 women, 84 were non or irregular (less than once a week) tea drinkers, 27 were regular (weekly/daily) green tea drinkers and 19 were regular (weekly/daily) black tea drinkers. Relative to plasma estrone levels in non- or irregular tea drinkers (29.5 pg/ml) the levels were 13% lower in regular green tea drinkers (25.8 pg/ml) and 19% higher in regular black tea drinkers (35.0 pg/ml). These differences in estrone levels were statistically significant (P = 0.03) inspite of adjusting for age, body mass index, intake of soy, and other covariates. A similar pattern of differences between tea intake, and plasma levels of estradiol (P = 0.08) and androstenedione (P = 0.14) were found. In addition, the tea-estrogen associations were observed irrespective of the genotype of catechol-O-methyltransferase (COMT), a major enzyme that aids in the excretion of tea polyphenols in humans. Larger studies are needed to confirm results from this cross-sectional study and to better understand the potentially differing effect of black and green tea on circulating estrogen levels and ultimately on the risk of breast cancer.     

Telomere length,oxidative damage,antioxidants and breast cancer risk

Telomeres play a critical role in maintaining the integrity and stability of the genome, and are susceptible to oxidative damage after telomere shortening to a critical length. In the present study, we explored the role of white blood cell DNA telomere length on breast cancer risk, and examined whether urinary 15‐F₂‐isoprostanes (15‐F_2t‐IsoP) and 8‐oxo‐7,8‐dihydrodeoxyguanosine (8‐oxodG) or dietary antioxidant intake modified the relationship between telomere length and breast cancer risk. A population‐based case–control study—the Long Island Breast Cancer Study Project—was conducted among 1,067 cases and 1,110 controls. Telomere length was assessed by quantitative PCR. Overall, the mean levels of telomere length (T/S ratio), 15‐F_2t‐IsoP and 8‐oxodG were not significantly different between cases and controls. Among premenopausal women only, carrying shorter telomeres (Q3 and Q4), as compared with the longest (Q1), was associated with significantly increased breast cancer risk. Age‐adjusted OR and 95% CI were 1.71 (1.10–2.67) and 1.61 (1.05–2.45). The 5‐F_2t‐IsoP and 8‐oxodG biomarkers did not modify the telomere–breast cancer association. A moderate increase in breast cancer risk was observed among women with the shortest telomeres (Q4) and lower dietary and supplemental intake of β‐carotene, vitamin C or E intake [OR (95% CI) = 1.48 (1.08–2.03), 1.39 (1.01–1.92) and 1.57 (1.14–2.18), respectively], although the trend test exhibited statistical significance only within the lower vitamin E intake subgroup (p_trend = 0.01). These results provided the strongest evidence to date that breast cancer risk may be affected by telomere length among premenopausal women or women with low dietary intake of antioxidants or antioxidant supplements. © 2008 Wiley‐Liss, Inc.     

Green tea and risk of breast cancer in Asian Americans

There is substantial in vitro and in vivo evidence implicating tea polyphenols as chemopreventive agents against various cancers. However, epidemiologic data obtained from mainly Western populations are not supportive of a protective role of tea, mainly black tea, in the etiology of breast cancer. Much less is known about the relationship between green tea and breast cancer risk. During 1995-1998, we conducted a population-based, case-control study of breast cancer among Chinese, Japanese and Filipino women in Los Angeles County and successfully interviewed 501 breast cancer patients and 594 control subjects. Detailed information on menstrual and reproductive factors; dietary habits, including intake of black and green tea; and other lifestyle factors was collected. Risk of breast cancer was not related to black tea consumption. In contrast, green tea drinkers showed a significantly reduced risk of breast cancer, and this was maintained after adjusting for age, specific Asian ethnicity, birthplace, age at menarche, parity, menopausal status, use of menopausal hormones, body size and intake of total calories and black tea. Compared to women who did not drink green tea regularly (i.e., less than once a month), there was a significant trend of decreasing risk with increasing amount of green tea intake, adjusted odds ratios being 1.00, 0.71 (95% confidence interval [CI] 0.51-0.99) and 0.53 (95% CI 0.35-0.78), respectively, in association with no, 0-85.7 and >85.7 ml of green tea per day. The significant inverse association between risk of breast cancer and green tea intake remained after further adjustment for other potential confounders, including smoking; alcohol, coffee and black tea intake; family history of breast cancer; physical activity; and intake of soy and dark green vegetables. While both green tea and soy intake had significant, independent protective effects on breast cancer risk, the benefit of green tea was primarily observed among subjects who were low soy consumers. Similarly, the protective effect of soy was primarily observed among subjects who were nondrinkers of green tea. In summary, our results point to an important role of both green tea and soy intake in relation to breast cancer risk in Asian-American women.     

Green tea intake, ACE gene polymorphism and breast cancer risk among Chinese women in Singapore

Experimental and epidemiological data have implicated a potential chemoprotective role of green tea polyphenols and a potential enhancing role of angiotensin II in the development of breast cancer in humans. Angiotensin II is converted from its precursor by angiotensin-converting enzyme (ACE). Women with low-activity genotype of the ACE gene had a reduced risk of breast cancer compared with those possessing high-activity ACE genotype. Experimental data showed that green tea polyphenols could inhibit angiotensin II-induced reactive oxygen species production. We reasoned that if this is one of the mechanisms by which green tea polyphenols protect against human breast cancer, then their effect should be more prominent among women possessing high-activity ACE genotype than women with low-activity ACE genotype. In other words, we predict a stronger inverse green tea-breast cancer association among the former versus the latter subgroup of women. To test this hypothesis, we conducted a nested case-control study involving 297 incident breast cancer cases and 665 control subjects within the Singapore Chinese Health Study. There was no association between intake frequencies of green tea and risk of breast cancer among all women or those with low-activity ACE genotype. Among women with high-activity ACE genotype, however, intake frequency of green tea was associated with a statistically significant decrease in risk of breast cancer (P for trend=0.039); the odds ratio (95% confidence interval) was 0.33 (0.13-0.82) for women drinking green tea at least monthly and 0.29 (0.10-0.79) for those drinking green tea at least weekly compared with non-drinkers. There was a statistically significant interaction effect between green tea intake and ACE genotype on risk of breast cancer (P for interaction=0.01). Black tea intake was unrelated to breast cancer risk irrespective of the ACE genotype. The findings of the present study highlight the importance of genetically determined factors in evaluating the role of green tea intake in the development of breast cancer.     

Do the dose or route of administration of norethisterone acetate as a part of hormone therapy play a role in risk of breast cancer: National‐wide case‐control study from Finland

We examined the associations between various doses and routes of administration of norethisterone acetate (NETA) in estrogen–progestagen therapy (EPT) and the risk of breast cancer in Finland. All Finnish women with first invasive breast cancer diagnosed between the ages of 50–62 during 1995–2007 (n = 9,956) were identified from the Finnish Cancer Registry. For each case, 3 controls of the same age were retrieved from the Finnish Population Register. The use of estradiol+NETA‐therapy by the cases and controls was traced from the national Medical Reimbursement Registry. The data were analyzed with multivariate conditional logistic regression, adjusting for parity, age at the first birth, and health care district. The continuous mode of NETA use tended to be associated with a higher rate ratio for breast cancer than the sequential use. The use of continuous “low” dose (NETA 0.5 mg + estradiol 1.0 mg) was associated with an increased rate ratio of breast cancer already in less than 3 years of use (odds ratio 1.94; 95% confidence interval 1.39–2.70) while a risk elevation for “high” dose (NETA 1.0 mg + estradiol 2.0 mg) was seen after 3 years use (1.71; 1.51–2.54). Oral and transdermal use of NETA were accompanied with comparable risks for breast cancer. In conclusion, the dose or route of administration of NETA in EPT do not modify the risks for breast cancer.     

Green tea drinking,high tea temperature and esophageal cancer in high‐ and low‐risk areas of Jiangsu Province,China: A population‐based case–control study

Epidemiological studies suggested drinking green tea is inversely associated with esophageal cancer but results remain inconclusive. Moreover, inconsistent observations found high temperature drinks are associated with esophageal cancer. A population‐based case–control study was conducted in a high‐risk area (Dafeng) and a low‐risk area (Ganyu) of esophageal cancer in Jiangsu province China from 2003 to 2007. It aimed to explore green tea drinking and tea temperature with the risk of esophageal cancer, and to compare the difference between different risk regions. Using identical protocols, 1,520 cases and 3,879 healthy controls were recruited as study subjects in 2 regions. Detailed information was collected to assess green tea drinking habits. Unconditional logistic regression was used to obtain OR and 95% CI. Results showed that ever drinking green tea elevated OR in both counties (Dafeng OR = 1.2, 95% CI = 0.9–1.5; Ganyu: OR = 1.9, 95% CI = 1.4–2.4). Drinking tea at high temperature was found to increase cancer risk in both areas (Dafeng: OR = 1.9, 95% CI = 1.2–2.9; Ganyu OR = 3.1 95% CI = 2.2–4.3). However, after further adjustment for tea temperature, ever drinking tea was not related to cancer in either county (Dafeng: OR = 1.0, 95% CI = 0.7–1.3; Ganyu: OR = 1.3, 95% CI = 0.9–1.7). For dose‐response relationships, we observed positive relationship with monthly consumption of tea (p for trend = 0.067) and tea concentration (p for trend = 0.006) after further adjustment for tea temperature. In conclusion, green tea drinking was not inversely associated with esophageal cancer in this study. However, drinking tea at high temperatures significantly increased esophageal cancer risk. There was no obvious difference of green tea drinking between low‐ and high‐risk areas. © 2008 Wiley‐Liss, Inc.     

Cadmium exposure and the risk of breast cancer in Japanese women

Non-occupational exposure to cadmium has been suspected to be a risk factor for breast cancer. The present study examined the association between urinary cadmium level and the risk of breast cancer in a case–control study among Japanese women. Cases were 153 women newly diagnosed and histologically confirmed with breast cancer at a general hospital in Gifu, Japan. A total of 431 controls individually matched to cases by age, menopausal status, and the period of urine sampling were selected from those who attended a breast cancer mass screening at this hospital. Urinary cadmium levels were measured using spot urine samples. Spot urine samples were collected from cases after surgery but before any cancer therapy. For controls, spot urine samples were obtained at the date of the screening visit. Information on known or suggested breast cancer risk factors was obtained by a self-administered questionnaire. The odds ratios (ORs) and 95 % confidence intervals (CIs) of breast cancer according to the tertile of the creatinine-adjusted cadmium level were calculated using conditional logistic regression models. Women in the highest tertile of the creatinine-adjusted cadmium level (>2.620 μg/g) had significantly elevated OR of breast cancer relative to those in the lowest tertile (<1.674 μg/g) after controlling for covariates [OR = 6.05, (95 % CI 2.90, 12.62)]. The trend of increase in risk with increasing cadmium level was also statistically significant [OR = 1.67, (95 % CI 1.39, 2.01) for every 1.0 μg/g increase in urinary cadmium level, P-trend <0.01]. These data suggested that exposure to cadmium was associated with a risk of breast cancer in Japanese women.     

Mammographic density,plasma vitamin D levels and risk of breast cancer in postmenopausal women

Mammographic density is a strong risk factor for breast cancer, but the underlying biology for this association is unknown. Studies suggest that vitamin D may reduce breast cancer risk and dietary vitamin D intake has been associated with reduced breast density. We conducted a case–control study nested within the Nurses' Health Study cohort consisting of 463 and 497 postmenopausal cases and controls, respectively. We examined the association between mammographic density and plasma levels of 25‐hydroxyvitamin D [25(OH)D] and 1,25‐dihydroxyvitamin D [1,25(OH)₂D]. We assessed whether plasma vitamin D metabolites modify the association between breast density and breast cancer. Percent mammographic density was measured from digitized film mammograms. Generalized linear models were used to determine mean percent breast density per quartile of vitamin D metabolite. Logistic regression models were used to calculate relative risks and confidence intervals. All models were adjusted for matching variables and potential confounders. We found no cross‐sectional association between circulating levels of 25(OH)D or 1,25(OH)₂D with mammographic density. Women in the highest tertile of mammographic density and lowest tertile of plasma 25(OH)D had 4 times greater risk of breast cancer than women with the lowest mammographic density and highest plasma 25(OH)D levels (RR = 3.8; 95% CI: 2.0–7.3). The overall interaction between mammographic density and plasma 25(OH)D was nonsignificant (p‐het = 0.20). These results indicate that the association between mammographic density and breast cancer is independent of plasma vitamin D metabolites in postmenopausal women. Further research examining vitamin D, mammographic density and breast cancer risk is warranted.     

The urinary excretion of corticosteroid sulfates by cancer patients.

Urinary excretions of free cortisol and corticosteroid sulfates were determined in 31 female controls, 77 breast cancer patients, 14 cases of colonic cancer, and 7 patients with bronchial carcinoma. Elevated corticosteroid sulfate excretion was present in 38% of patients with locally recurrent breast cancer and 30% of those with distant metastases, but in only 13% of the "early" breast cancer cases. A similar abnormality was seen in colonic cancer. Urinary free cortisol was usually normal. ACTH stimulation in a normal subject produced marked increases of both urinary free cortisol and corticosteroid sulfates. It is concluded that elevated corticosteroid sulfate excretion in cancer patients arises from an increased cortisol production rate combined with increased sulfurylation of the steroid. In bronchial carcinoma patients, changes similar to those occurring in the ACTH-treated normal subject may have resulted from ectopic ACTH production in the tumor.