Dietary factors protective against breast cancer in Japanese premenopausal and postmenopausal women

Since components of the Japanese diet that might be responsible for the relatively low breast cancer incidence rates observed in Japan have not been clarified in detail, a case-referent study with reference to menopausal status was conducted using data from the hospital-based epidemiologic research program at Aichi Cancer Center (HERPACC). In total, 2,385 breast cancer cases were included, and 19,013 women, confirmed as free of cancer, were recruited as the reference group. Odds ratios (ORs) and 95% confidence intervals (95% CIs) were determined by multiple logistic regression analysis. There were reductions in risk associated with high intake of milk and green-yellow vegetables (green leafy vegetables, carrots and pumpkins) among both pre- and postmenopausal women. The protective effects of the Japanese diet were more prominent among postmenopausal than premenopausal women. The adjusted OR of fish consumption (5 or more times per week vs. fewer than 3 times per month) was 0.75 (95% CI 0.57-0.98, p(trend) = 0.01) for postmenopausal breast cancer. A significant decrease in postmenopausal breast cancer risk was also observed for increasing intake of fruit (OR = 0.61, 95% CI 0.41-0.91). Thus, traditional Japanese dietary factors may protect against breast cancer development, especially among postmenopausal women.     

Intake of fruits,vegetables and selected micronutrients in relation to the risk of breast cancer

High fruit and vegetable intake has been linked with a reduced risk of breast cancer, but evidence is not consistent. We investigated the associations of breast cancer risk with vegetables, fruits and related micronutrient intake in a population-based case-control study among Chinese women in Shanghai, where dietary patterns differ substantially from other study populations. Included in the study were 1,459 incident breast cancer cases and 1,556 frequency-matched controls. Usual dietary habits were assessed by in-person interviews. Logistic regression was used to compute adjusted odds ratios (ORs) and 95% confidence intervals (CIs) to measure strength of the associations. There was no association between breast cancer risk and total vegetable intake. The risk of breast cancer declined, however, with increasing intake of dark yellow-orange vegetables (trend test, p = 0.02), Chinese white turnips (trend test, p 相似文献   

Case-control study of anthropometric measures and breast cancer risk

A population-based case-control study of 1,233 incident breast cancer cases and 1,241 controls was conducted in Alberta between 1995 and 1997 to examine the influence of anthropometric factors on the risk of breast cancer using several newly derived variables. Data on current height, weight and waist and hip circumference were collected by interviewers using standardized methods. Respondents recalled their body weight at each decade from age 20 to the referent year. Several variables were estimated, and unconditional logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (95% CIs). No statistically significant associations for any of the estimated variables with breast cancer risk for premenopausal women (462 cases, 475 controls) were found. The results for postmenopausal women (771 cases, 762 controls) in the highest vs. lowest quartiles were, for waist circumference, OR = 1.30 (95% CI 0.97-1.73); waist-hip ratio, OR = 1.43 (95% CI 1.07-1.93); weight gain since age 20, OR = 1.35 (05% CI 1.01-1.81); difference between maximum and minimum weights over adult lifetime, OR = 1.56 (95% CI 1.16-2.08); and the reference weight minus the minimum weight since age 20, OR = 1.47 (95% CI 1.10-1.97). Statistically significant trends in risk were observed for these variables. Effect modification with hormone replacement therapy use was found for most variables assessed for postmenopausal women, with much stronger associations found among never-users compared to ever-users. We found strong evidence that waist-hip ratio and weight gained over lifetime, as assessed by different variables, are postmenopausal breast cancer risk factors. These effects were independent of dietary intake and lifetime total physical activity.     

Dietary carotenoids and the risk of invasive breast cancer

Certain classes of vitamins and nutrients found in fruits and vegetables have been of particular interest in relation to cancer prevention, owing to their potential anticarcinogenic properties. We examined the association between certain fruits, vegetables, carotenoids, and vitamin A and breast cancer risk in a large population‐based case‐control study of women residing in the states of Massachusetts, New Hampshire and Wisconsin. The study was comprised of 5,707 women with incident invasive breast cancer (2,363 premenopausal women and 3,516 postmenopausal women) and 6,389 population controls (2,594 premenopausal women and 3,516 postmenopausal women). In an interview, women were asked about their intake of carotenoid rich fruits and vegetables 5 years prior to a referent date. An inverse association observed among premenopausal women was for high levels of vitamin A (OR: 0.82, 95% CI: 0.68–0.98, p for trend = 0.01), β‐carotene (OR: 0.81, 95% CI 0.68–0.98, p for trend = 0.009), α‐carotene (OR: 0.82, 95% CI: 0.68–0.98, p for trend = 0.07) and lutein/zeaxanthin (OR: 0.83, 95% CI 0.68–0.99, p for trend = 0.02). An inverse association was not observed among postmenopausal women. Among premenopausal women who reported ever smoking, these results were stronger than among never smokers, although tests for interaction were not statistically significant. Results from this study are comparable to previous prospective studies, and suggest that a high consumption of carotenoids may reduce the risk of premenopausal but not postmenopausal breast cancer, particularly among smokers. © 2009 UICC     

Dietary carotenoids and vitamins A, C, and E and risk of breast cancer

BACKGROUND: Data on intake of specific carotenoids and breast cancer risk are limited. Furthermore, studies of vitamins A, C, and E in relation to breast cancer risk are inconclusive. We have conducted a large, prospective study to evaluate long-term intakes of these nutrients and breast cancer risk. METHODS: We examined, by use of multivariate analysis, associations between intakes of specific carotenoids, vitamins A, C, and E , consumption of fruits and vegetables, and breast cancer risk in a cohort of 83234 women (aged 33-60 years in 1980) who were participating in the Nurses' Health Study. Through 1994, we identified 2697 incident cases of invasive breast cancer (784 premenopausal and 1913 postmenopausal). RESULTS: Intakes of beta-carotene from food and supplements, lutein/zeaxanthin, and vitamin A from foods were weakly inversely associated with breast cancer risk in premenopausal women. Strong inverse associations were found for increasing quintiles of alpha-carotene, beta-carotene, lutein/zeaxanthin, total vitamin C from foods, and total vitamin A among premenopausal women with a positive family history of breast cancer. An inverse association was also found for increasing quintiles of beta-carotene among premenopausal women who consumed 15 g or more of alcohol per day. Premenopausal women who consumed five or more servings per day of fruits and vegetables had modestly lower risk of breast cancer than those who had less than two servings per day (relative risk [RR] = 0.77; 95% confidence interval [CI] = 0.58-1.02); this association was stronger among premenopausal women who had a positive family history of breast cancer (RR = 0.29; 95% CI = 0.13-0.62) or those who consumed 15 g or more of alcohol per day (RR = 0.53; 95% CI = 0.27-1.04). CONCLUSIONS: Consumption of fruits and vegetables high in specific carotenoids and vitamins may reduce premenopausal breast cancer risk.     

Soybean products and reduction of breast cancer risk: a case-control study in Japan

Components of the Japanese diet, which might contribute to the relatively low breast cancer incidence rates in Japan, have not been clarified in detail. Since soybean products are widely consumed in Japan, a case-control study taking account of the menopausal status was conducted using data from the hospital-based epidemiologic research program at Aichi Cancer Center (HERPACC). In total, 167 breast cancer cases were included and 854 women confirmed as free of cancer were recruited as the control group. Odds ratios (OR) and 95% confidence intervals (95% CI) were determined by multiple logistic regression analysis. There were reductions in risk of breast cancer associated with high intake of soybean products among premenopausal women. Compared with women in the lowest tertile, the adjusted ORs for top tertile intake of tofu (soybean curd) was 0.49 (95% CI, 0.25-0.95). A significant decrease in premenopausal breast cancer risk was also observed for increasing consumption of isoflavones (OR=0.44; 95% CI, 0.22-0.89 for highest vs lowest tertile; P for trend=0.02). The present study found a statistically inverse association between tofu or isoflavone intake and risk of breast cancer in Japanese premenopausal women, while no statistically significant association was evident with the risk among postmenopausal women.     

A case-control study on the dietary intake of mushrooms and breast cancer risk among Korean women

To evaluate the association between dietary mushroom intake and breast cancer risk, a total of 362 women between the ages of 30 and 65 years who were histologically confirmed to have breast cancer were matched to controls by age (+/-2 years) and menopausal status. Mushroom intake was measured via a food frequency questionnaire that was administered by well-trained interviewers. The associations between the daily intake and the average consumption frequency of mushrooms with breast cancer risk were evaluated using matched data analysis. Both the daily intake (5th vs. 1st quintile, OR = 0.48, 95% CI = 0.30-0.78, p for trend 0.030) and the average consumption frequency of mushrooms (4th vs. 1st quartile, OR = 0.54, 95% CI = 0.35-0.82, p for trend 0.008) were inversely associated with breast cancer risk after adjustment for education, family history of breast cancer, regular exercise [>or=22.5 MET (metabolic equivalent)-hr/week], BMI (body mass index, Kg/m(2)), number of children and whether they are currently smoking, drinking or using multivitamin supplements. Further adjustments were made for energy-adjusted carbohydrate, soy protein, folate and vitamin E levels, which tended to attenuate these results. After a stratification was performed according to menopausal status, a strong inverse association was found in postmenopausal women (OR = 0.16, 95% CI = 0.04-0.54, p for trend = 0.0058 for daily intake; OR = 0.17, 95% CI = 0.05-0.54, p for trend = 0.0037 for average frequency), but not in premenopausal women. In conclusion, the consumption of dietary mushrooms may decrease breast cancer risk in postmenopausal women.     

Serum carotenoid,tocopherol and retinol concentrations and breast cancer risk in the E3N‐EPIC study

Evidence of a protective effect of fruit and vegetable intake on breast cancer risk is inconsistent. Epidemiologic cohort studies based on blood carotenoid intakes as biomarkers of consumption of fruits and vegetable in individuals are still scare and findings are discrepant. The study population included women in the E3N Study, the large French component of the European Prospective Investigation into Cancer and Nutrition (EPIC). During an average of 7 years follow‐up, 366 cases of incident invasive breast cancer (84 premenopausal women and 282 postmenopausal women) among 19,934 women who completed a dietary questionnaire and had available blood samples at baseline (1995–1998) were included in the study. Controls were randomly matched on age, menopausal status at blood collection, fasting status at blood collection, date and collection center. Serum carotenoids, tocopherols and retinol concentrations were assessed by high pressure liquid chromatography. Odds ratios for breast cancer risk adjusted for established breast cancer risk factors were calculated by quintile of serum micronutrient concentrations. No significant associations between breast cancer risk and serum carotenoids (highest versus lowest quintile, odds ratio (OR) = 0.74, 95% confidence interval (CI) = 0.47–1.16, p for trend 0.38), tocopherols (OR = 0.68, 95% CI = 0.41–1.10, p for trend 0.26) and retinol (OR = 0.85, 95% CI = 0.53–1.35, p for trend 0.34) were found. Our findings did not support the hypothesis that lipophilic antioxidant micronutrients found in fruits and vegetables protect against breast cancer, at least in postmenopausal women.     

Associations of dietary folate,Vitamins B6 and B12 and methionine intake with risk of breast cancer among African American and European American women

African American (AA) women are more likely than European American (EA) women to be diagnosed with breast cancer at younger ages and to develop poor prognosis tumors. However, these racial differences are largely unexplained. Folate and other methyl‐group nutrients may be related to breast carcinogenesis, but few studies have examined these associations in AA populations. We examined the associations of dietary intake of these nutrients with breast cancer risk overall, by menopausal and estrogen receptor (ER) status among 1,582 AA (749 cases) and 1,434 EA (744 cases) women using data from a case–control study, the Women's Circle of Health Study. Unconditional multivariable logistic regression models were used to compute odds ratios (ORs) and 95% confidence intervals (CIs) for the association of each nutrient and breast cancer risk. In AA women, inverse associations were observed for natural food folate intake among premenopausal women (fourth vs. first quartile: OR = 0.57, 95% CI, 0.33–1.00; p for trend = 0.06) and for ER‐positive tumors (fourth vs. first quartile: OR = 0.58, 95% CI, 0.36–0.93; p for trend = 0.03), whereas in EA women, a positive association was observed for intake of synthetic folate (fourth vs. first quartile: OR = 1.53, 95% CI, 1.06–2.21; p for trend = 0.03). Our findings suggest that natural food folate intake is inversely associated with breast cancer risk and that this association may vary by race, menopausal status or ER status. The finding of an increased risk observed among EA women with the highest intake of synthetic folate from fortified foods warrants further investigation.     

Glutathione S-transferase M1, M3, P1, and T1 genetic polymorphisms and susceptibility to breast cancer.

This study was undertaken to examine if glutathione S-transferase (GST) M1, M3, P1, and T1 genotypes affected breast cancer risk in Finnish women. The study population consisted of 483 incident breast cancer cases and 482 healthy population controls. Genotyping analyses were performed by PCR-based methods, and odds ratios (ORs) and 95% confidence intervals (CIs) were calculated by unconditional logistic regression adjusting for known or suspected risk factors for breast cancer. When the genes were studied separately, the only significant finding was between GSTM1 null genotype and postmenopausal breast cancer risk (OR, 1.49; 95% CI, 1.03-2.15). Conversely, when the potential combined effects of the at-risk genotypes were examined, significant associations were observed only among premenopausal women. Although only a moderate risk of breast cancer was seen for premenopausal women concurrently carrying the GSTM3*B allele containing genotypes and the GSTP1 Ile/ Ile genotype (OR, 2.07; 95% CI, 1.02-4.18), the risk rose steeply if they simultaneously lacked the GSTT1 gene (OR, 9.93, 95% CI, 1.10-90.0). A borderline significant increase in the risk of breast cancer was also seen for premenopausal women with the combination of GSTM1 null, GSTP1 Ile/Ile, and GSTT1 null genotypes (OR, 3.96; 95% CI, 0.99-15.8). Our findings support the view that GST genotypes contribute to the individual breast cancer risk, especially in certain combinations.     

Fruits, vegetables, and micronutrient intake in relation to breast cancer survival

SummaryObjective To determine whether fruit, vegetable, and micronutrient intake 1 year prior to breast cancer diagnosis is associated with a reduction in the subsequent risk of all-cause or breast cancer-specific mortality.Methods Follow-up data from 1,235 invasive breast cancer cases age 25–98 years from the Long Island Breast Cancer Study Project were analyzed. At the 1996–1997 case-control interview, respondents completed a food frequency questionnaire, which assessed dietary intake of fruits, vegetables, and vitamin supplement use in the previous 12 months. All-cause mortality (n=186 deaths) and breast cancer-specific mortality status (n=125 deaths, 67.2%) were determined through December 31, 2002.Results Hazard ratios (HRs) for all-cause mortality were insignificantly reduced for intake of any fruits, fruit juices, and vegetables (HR=0.68, 95% CI: 0.42–1.09) and leafy vegetables (HR=0.72, 95% CI: 0.41–1.24) among post-menopausal women only. Both of these associations were more pronounced among those with ER+PR+ tumors (HR=0.54, 95% CI: 0.27–1.10, and HR=0.66, 95% CI: 0.33–1.31, respectively). Similar associations were observed for breast cancer-specific mortality.Conclusions In a cohort of women diagnosed with breast cancer, higher intake of fruits, vegetables, and micronutrients was associated with a non-significant survival advantage in post-menopausal women only.     

Fruit and vegetable intake and breast cancer risk defined by estrogen and progesterone receptor status: the Japan Public Health Center-based Prospective Study

Background

Epidemiological evidence for the impact of fruit and vegetable intake on breast cancer risk among the Japanese populations is scarce.

Objective

The purpose of this study was to evaluate the association between fruit and vegetable intake and breast cancer risk among 47,289 Japanese women.

Design

The study was conducted under a population-based prospective cohort design. Dietary assessment was performed using a validated food frequency questionnaire. A Cox proportional hazards regression model was used to calculate relative risks (RRs) and their corresponding 95 % confidence intervals (CIs).

Results

During an average of 10.2 years of follow-up, 452 cases of breast cancer were newly diagnosed. No association with breast cancer risk was seen for intake of total fruits and vegetables, cruciferous vegetables, green-leaf vegetables, yellow vegetables, or tomato products in overall or postmenopausal women. Cruciferous vegetable intake was associated with a statistically significant decrease in risk of premenopausal breast cancer [multivariable-RR_{Q4 vs. Q1} = 0.64 (95 % CI = 0.38–1.10; p _trend = .046)] and showed a marginally inverse association with ER+ PR+ tumors [RR_{per 100 g increment} = 0.64 (95 % CI = 0.41–1.00)]. In contrast, positive associations were seen between intake of total fruits and citrus fruits and breast cancer risk in overall and premenopausal women. However, these associations for fruit were all attenuated with additional adjustment for vitamin C intake.

Conclusions

Our results suggest an overall null association between total fruit and vegetable intake and breast cancer risk. Intake of cruciferous vegetable showed a statistically significant association with a decreased risk of breast cancer among premenopausal women.     

Premenopausal levels of circulating insulin-like growth factor I and the risk of postmenopausal breast cancer

Increased levels of insulin-like growth factor I (IGF-I) may directly stimulate breast cell proliferation and promote growth and survival of transformed cells. Higher levels of IGF-I have been associated with increased risk of premenopausal breast cancer but not postmenopausal breast cancer. We investigated whether circulating levels of IGF-I prior to menopause are associated with breast cancer diagnosed after menopause in a population-based nested case-control study. Female cohort participants were enrolled in 1974 (n = 15,192) and 1989 (n = 18,724) and blood was drawn. Cases were women diagnosed with primary breast cancer at ages > or =50, of whom 152 were premenopausal at blood draw. One control was matched to each case on cohort participation, age, ethnic group, menopausal status and date of blood draw. Levels of IGF-I and IGF binding protein 3 (IGFBP-3) were measured using enzyme-linked immunoabsorbent assays. The association between IGF-I and breast cancer was determined using conditional logistic regression, adjusting for IGFBP-3. IGF-I levels decreased with age (p = 0.0001). Prior to age-stratification, IGF-I levels neither measured before nor after menopause were associated with postmenopausal breast cancer. After age-stratification, associations were suggested in the youngest premenopausal age group (upper vs. lowest third: odds ratio (OR) = 5.31, 95% confidence intervals (CI) = 0.85-33.13; p trend = 0.06) and oldest postmenopausal age group (upper vs. lowest third: OR = 3.41, 95% CI = 0.66-17.71; p trend = 0.13). The association between circulating levels of IGF-I and postmenopausal breast cancer risk may be modified by age. Increased levels of circulating IGF-I may be of particular interest in the younger premenopausal women and older postmenopausal women. Age-stratification should be undertaken in larger investigations of IGF-I levels as predictors of postmenopausal breast cancer.     

Dairy, calcium, and vitamin D intake and postmenopausal breast cancer risk in the Cancer Prevention Study II Nutrition Cohort.

BACKGROUND: Calcium, vitamin D, and dairy products are highly correlated factors, each with potential roles in breast carcinogenesis. Few prospective studies have examined these relationships in postmenopausal women.METHODS: Participants in the Cancer Prevention Study II Nutrition Cohort completed a detailed questionnaire on diet, vitamin and mineral supplement use, medical history, and lifestyle in 1992 to 1993. After exclusion of women with a history of cancer and incomplete dietary data, 68,567 postmenopausal women remained for analysis. During follow-up through August 31, 2001, we identified 2,855 incident cases of breast cancer. Multivariate-adjusted rate ratios (RR) were calculated using Cox proportional hazards models.RESULTS: Women with the highest intake of dietary calcium (>1,250 mg/d) were at a lower risk of breast cancer than those reporting < or =500 mg/d [RR, 0.80; 95% confidence interval (95% CI), 0.67-0.95; P(trend) = 0.02]; however, neither use of supplemental calcium nor vitamin D intake was associated with risk. Consumption starting at two or more servings of dairy products per day was likewise inversely associated with risk (RR, 0.81; 95% CI, 0.69-0.95; P(trend) = 0.002, compared with <0.5 servings/d). The associations were slightly stronger in women with estrogen receptor-positive tumors comparing highest to lowest intake: dietary calcium (RR, 0.67; 95% CI, 0.51-0.88; P(trend) = 0.004); dairy products (RR, 0.73; 95% CI, 0.57-0.93; P(trend) = 0.0003), and dietary vitamin D (RR, 0.74; 95% CI, 0.59-0.93; P(trend) = 0.006).CONCLUSIONS: Our results support the hypothesis that dietary calcium and/or some other components in dairy products may modestly reduce risk of postmenopausal breast cancer. The stronger inverse associations among estrogen receptor-positive tumors deserve further study.     

Dietary cadmium exposure and risk of postmenopausal breast cancer: a population-based prospective cohort study

The ubiquitous food contaminant cadmium has features of an estrogen mimetic that may promote the development of estrogen-dependent malignancies, such as breast cancer. However, no prospective studies of cadmium exposure and breast cancer risk have been reported. We examined the association between dietary cadmium exposure (at baseline, 1987) and the risk of overall and estrogen receptor (ER)-defined (ER(+) or ER(-)) breast cancer within a population-based prospective cohort of 55,987 postmenopausal women. During an average of 12.2 years of follow-up, 2,112 incident cases of invasive breast cancer were ascertained (1,626 ER(+) and 290 ER(-)). After adjusting for confounders, including consumption of whole grains and vegetables (which account for 40% of the dietary exposure, but also contain putative anticarcinogenic phytochemicals), dietary cadmium intake was positively associated with overall breast cancer tumors, comparing the highest tertile with the lowest [rate ratio (RR), 1.21; 95% confidence interval (CI), 1.07-1.36; P(trend) = 0.02]. Among lean and normal weight women, statistically significant associations were observed for all tumors (RR, 1.27; 95% CI, 1.07-1.50) and for ER(+) tumors (RR, 1.25; 95% CI, 1.03-1.52) and similar, but not statistically significant associations were found for ER(-) tumors (RR, 1.22; 95% CI, 0.76-1.93). The risk of breast cancer increased with increasing cadmium exposure similarly within each tertile of whole grain/vegetable consumption and decreased with increasing consumption of whole grain/vegetables within each tertile of cadmium exposure (P(interaction) = 0.73). Overall, these results suggest a role for dietary cadmium in postmenopausal breast cancer development.     

A prospective study of serum insulin-like growth factor-I (IGF-I), IGF-II, IGF-binding protein-3 and breast cancer risk

The associations between serum concentrations of insulin-like growth factor-I (IGF-I), IGF-II and IGF-binding proteins (IGFBP)-3 and risk of breast cancer were investigated in a nested case-control study involving 117 cases (70 premenopausal and 47 postmenopausal at blood collection) and 350 matched controls within a cohort of women from the island of Guernsey, UK. Women using exogenous hormones at the time of blood collection were excluded. Premenopausal women in the top vs bottom third of serum IGF-I concentration had a nonsignificantly increased risk for breast cancer after adjustment for IGFBP-3 (odds ratio (OR) 1.71; 95% confidence interval (CI): 0.74-3.95; test for linear trend, P=0.21). Serum IGFBP-3 was associated with a reduction in risk in premenopausal women after adjustment for IGF-I (top third vs the bottom third: OR 0.49; 95% CI: 0.21-1.12, P for trend=0.07). Neither IGF-I nor IGFBP-3 was associated with risk in postmenopausal women and serum IGF-II concentration was not associated with risk in pre- or postmenopausal women. These data are compatible with the hypothesis that premenopausal women with a relatively high circulating concentration of IGF-I and low IGFBP-3 are at an increased risk of developing breast cancer.     

Polymorphic catechol-O-methyltransferase gene and breast cancer risk.

We examined 483 Finnish breast cancer cases and 482 population controls to determine the potential effect of catechol-O-methyltransferase (COMT) genotype in individual susceptibility to breast cancer. Odds ratios (ORs) and 95% confidence intervals (CIs) were estimated by unconditional logistic regression after adjustment for known or suspected risk factors for breast cancer. When studied separately by menopausal status, the COMT-L allele-containing genotypes were inversely associated with premenopausal breast cancer, especially with advanced stage of the disease (OR, 0.44; 95% CI, 0.22-0.87). Among postmenopausal women a similar decreased risk was seen for local carcinoma associated with the COMT-LL genotype (OR, 0.55; 95% CI, 0.31-0.98). The lowest breast cancer risk was seen in the postmenopausal women with the COMT-LL genotype and low body-mass index (30 months) use of estrogen (OR, 4.02; 95% CI, 1.13-14.3), or with the COMT-L allele-containing genotypes and early age (相似文献   

IGF-I and breast cancer: a meta-analysis

IGFs are peptide hormones involved in the regulation of cell proliferation, differentiation and apoptosis. IGFs are regulated by endocrine and paracrine mechanisms; however, their action in tissue is determined by circulating levels and local production of IGFs and IGF-binding proteins (IGFBPs). Some, but not all, epidemiologic studies have associated high circulating levels of IGF-I with increased risk of breast cancer among premenopausal women. To evaluate the overall association of IGF-I and IGFBP-3 levels with breast cancer risk, we performed a meta-analysis on 16 publications of epidemiologic and clinical studies. Analyses were performed for all women as well as for pre- and postmenopausal women separately. Hedges' standardized mean differences (HSMDs) and odds ratios (ORs) were used to estimate the effect of IGF-I and IGFBP-3. Data analysis showed that circulating levels of IGF-I were not significantly higher in breast cancer patients than in controls for all women and for the postmenopausal group (HSMD = 0.024 and 0.035, respectively; p > 0.40) but were significantly higher (HSMD = 0.170, p < 0.001) for the premenopausal group. ORs for breast cancer risk were 1.05 (95% CI 0.94-1.17), 0.93 (95% CI 0.80-1.10) and 1.39 (95% CI 1.16-1.66). The HSMD of IGFBP-3 was 0.18 (p < 0.001), and the OR for breast cancer was 1.42 (95% CI 1.15-1.74) for premenopausal women. Our results support the suggested association between high IGF-I and IGFBP-3 levels and increased risk of breast cancer in premenopausal women.     

ADH3 genotype, alcohol intake and breast cancer risk

Moderate alcohol consumption of approximately 1-2 drinks per day has been associated with a 30-50% increase in breast cancer risk. Individuals differ in their ability to metabolize alcohol through genetic differences in alcohol dehydrogenase (ADH), the enzyme that catalyzes the oxidation of approximately 80% of ethanol to acetaldehyde, a known carcinogen. Individuals differ in their ADH genotype, and one locus in particular (ADH3) is polymorphic in Caucasian populations. Using data from the Long Island Breast Cancer Study Project, we examined whether fast metabolizers of alcohol, as measured by the ADH3(1-1) genotype, have a higher risk of breast cancer from alcohol intake compared with those individuals who are slow metabolizers, but consume similar amounts of alcohol. We combined genotyping information with questionnaire data on 1047 breast cancer cases and 1101 controls and used unconditional logistic regression methods to estimate multivariate-adjusted odds ratios (ORs) and 95% confidence intervals (CIs) between alcohol intake and breast cancer risk. Among individuals homozygous for the fast metabolizing allele (ADH(3)1-1), a lifetime alcohol consumption of 15-30 g/day (approximately 1-2 drinks per day) increased breast cancer risk by 2-fold (OR=2.0, 95% CI=1.1-3.5). In contrast, the increase in risk from a lifetime alcohol consumption of 15-30 g/day was less pronounced in the intermediate and slow metabolizing groups, respectively: ADH3(1-2) (OR=1.5, 95% CI 0.9-2.4) and ADH(3)2-2 (OR=1.3, 95% CI 0.5-3.5). Fast metabolizers who drank 15-30 g/day of alcohol had 2.3 times (95% CI 1.3-4.0) greater risk of breast cancer than non-drinkers who were intermediate or slow metabolizers. This association for fast metabolizers who drank 15-30 g/day was particularly pronounced among premenopausal women (premenopausal women OR=2.9, 95 % CI=1.2-7.1; postmenopausal women OR=1.8, 95% CI=0.9-3.8). These population-based data support the hypothesis that fast metabolizers of alcohol have a higher risk of breast cancer risk, from alcohol intake than slow metabolizers.     

Phytoestrogen intake from foods,during adolescence and adulthood,and risk of breast cancer by estrogen and progesterone receptor tumor subgroup among Ontario women

Phytoestrogen intake may reduce breast cancer risk and limited evidence suggests this association may hold for hormone receptor‐positive tumors only. The study aims were to assess whether the association between phytoestrogen intake during adolescence and adulthood and breast cancer risk varies by estrogen and progesterone receptor (ERPR) tumor subgroup. Cases were identified from the Ontario Cancer Registry (2002–2003), and ERPR status was ascertained from pathology reports for 81% of cases (n = 2,438). Controls were identified through random digit dialing of Ontario households (n = 3,370). Published phytoestrogen food values were applied to food frequency questionnaire responses to assess isoflavone, lignan and total phytoestrogen intake, during adolescence and adulthood. Polytomous multivariate logistic regression was used to estimate adjusted odds ratios (ORs) for association between phytoestrogen intake and breast cancer risk by hormone receptor ERPR tumor subgroups. Among premenopausal women, few associations were observed for adolescent or adult phytoestrogen intake across all tumor subgroups. Among postmenopausal women, adolescent phytoestrogen intake (isoflavone, lignan and total) was associated with reduced risk across all hormone receptor subgroups; however, statistical significance was most consistent within the ER+PR+ subgroup. For example, ER+PR+ postmenopausal breast cancer risk was associated with adolescent phytoestrogen intake (highest vs. lowest: OR = 0.79; 95% confidence interval: 0.65–0.96). Among all women and postmenopausal women, ORs for high adult lignan intake were all below 1.0 within each tumor subgroup, suggesting reduced breast cancer risk, although none reached statistical significance. In conclusion, adolescent phytoestrogen intake was associated with reduced postmenopausal breast cancer, particularly for ER+PR+ tumor subgroup.