Expression of estrogen receptors in non-malignant mammary tissue modifies the association between insulin-like growth factor 1 and breast cancer risk.

BACKGROUND: Several studies have reported that the insulin-like growth factor 1 (IGF-1) is positively associated with estrogen receptor-positive [ER(+)] breast cancer risk, whereas there is little or no association with respect to ER(-) breast cancer. All comparisons of ER(+) breast cancer cases, however, have been made versus healthy controls, for whom there is no information about the ER expression in their mammary gland. PATIENTS AND METHODS: In the context of a case-control investigation conducted in Athens, Greece, we studied 102 women with incident ERα(+) breast cancer and compared their IGF-1 blood levels with those of 178 ERα(+) and 83 ERα(-) women with benign breast disease (BBD) who underwent biopsies in the context of their standard medical care. Data were analysed using multiple logistic regression and controlling for potential confounding variables. RESULTS: ERα(+) breast cancer patients had higher IGF-1 levels compared with women with BBD [odds ratio (OR) 1.36, 95% confidence interval (CI): 0.95-1.94, per 1 standard deviation (SD) increase in IGF-1 levels]. When ERα status of women with BBD was taken into account, the difference in IGF-1 levels between ERα(+) breast cancer patients and women with BBD was clearly driven by the comparison with BBD women who were ERα(+) (OR = 1.95, 95% CI: 1.31-2.89 per 1 SD increase in IGF-1 levels), whereas there was essentially no association with IGF-1 levels when ERα(+) breast cancer patients were compared with ERα(-) BBD women. These contrasts were particularly evident among post/peri-menopausal women. CONCLUSIONS: We found evidence in support of an interaction of IGF-1 with the expression of ERα in the non-malignant mammary tissue in the context of breast cancer pathogenesis. This is in line with previous evidence suggesting that IGF-1 increases the risk of ER(+) breast cancer.

A comparison of hormonal profiles between breast cancer and benign breast disease: a case-control study.

BACKGROUND: Benign breast disease (BBD), particularly proliferative BBD, is an established breast cancer risk factor. However, there has been no systematic attempt to compare the hormonal profiles of the two conditions. In a case-control investigation in Athens, Greece, we compared levels of estrogens, testosterone and insulin-like growth factor-1 (IGF-1), as well as their principal binding proteins, between breast cancer patients, women with BBD by histological type (proliferative and nonproliferative) and women with no breast pathology. PATIENTS AND METHODS: We studied 466 women with incident breast cancer, 704 women with BBD and 244 healthy women. We used multiple regression to compare log-transformed serum hormone levels of breast cancer patients with those of healthy women and women with BBD by histological type (proliferative and nonproliferative BBD). RESULTS: The hormonal profile of breast cancer in our study was in line with the generally accepted hormonal profile of this disease, as reported from large cohort studies. Compared with healthy women, breast cancer patients tended to have higher levels of steroid hormones. The evidence was strong for estrone (difference 21.5%, P < 0.001), weaker for testosterone (difference 15.8%, P = 0.07) and weaker still for estradiol (difference 12.0%, P = 0.18). Also compared with healthy women, breast cancer patients had barely higher levels of IGF-1 (difference 2.0%, P = 0.51), but had significantly lower levels of IGF binding protein 3 (IGFBP-3) (difference -6.7%, P = 0.001). Compared with women with BBD, breast cancer patients had nonstatistically significantly lower levels of steroid hormones, but they had higher levels of IGF-1 [difference 5.5%, 95% confidence interval (CI) 0.7% to 10.6%] and lower levels of IGFBP-3 (difference -3.7%, 95% CI -6.7% to -0.7%). Differences were more pronounced when breast cancer patients were contrasted to women with proliferative BBD. CONCLUSIONS: Our findings suggest that high levels of IGF-1 may be an important factor toward the evolution of BBD to breast cancer.

The hormonal profile of benign breast disease.

BACKGROUND: Limited information exists about the endocrine milieu of benign breast disease (BBD), a documented breast cancer risk factor. We compared blood levels of estrogens, testosterone and insulin-like growth factor-1 (IGF-1) between BBD patients by histological type and women without breast pathology. METHODS: We studied 578 BBD patients and 178 healthy women in Athens, Greece, who provided blood samples, and completed interviewer-administered questionnaires. RESULTS: Of the BBD patients, 254 had non-proliferative disease, 268 proliferative disease without atypia and 56 atypical hyperplasia. Comparing BBD patients with healthy women, the per cent differences (and 95% confidence intervals) for blood hormones, among pre-menopausal and peri/post-menopausal women, respectively, were: 22.4% (-4.0%, 56.1%) and 32.0% (5.6%, 65.1%) for estradiol; 26.2% (10.1%, 44.8%) and 30.9% (16.8%, 46.6%) for estrone; 19.5% (3.1%, 38.4%) and 16.5% (-5.0%, 42.9%) for testosterone; and -5.2% (-13.8%, 4.4%) and -12.1% (-19.8%, -3.6%) for IGF-1. Steroid hormones tended to be higher in proliferative compared with non-proliferative BBD. CONCLUSIONS: Circulating steroid hormones tend to be higher among women with BBD than women with no breast pathology and higher in proliferative than non-proliferative disease; these patterns are more evident among peri/post-menopausal women. In peri/post-menopausal women IGF-1 was lower among women with BBD compared with healthy women.

Maternal and cord blood hormone levels in the United States and China and the intrauterine origin of breast cancer.

BACKGROUND: Breast cancer is less common in China than in the United States and perinatal characteristics predict breast cancer risk in the offspring. We determined levels of pregnancy hormones in Boston and Shanghai to identify those possibly involved in the intrauterine origin of breast cancer. PARTICIPANTS AND METHODS: We compared maternal and cord blood levels of estradiol, estriol, testosterone, progesterone, prolactin, insulin-like growth factors (IGF) 1 and 2, insulin-like growth factor-binding protein 3, adiponectin and sex hormone-binding globulin (SHBG) in 241 Caucasian and 295 Chinese women. RESULTS: In both centers, hormone levels at the 16th were predictive of those at the 27th gestational week, but there was little correlation between maternal and cord blood levels. In cord blood, we found significantly (P < 0.01) higher levels of estradiol (44.2%), testosterone (54.5%), IGF-2 (22.7%) and strikingly SHBG (104.6%) in Shanghai women, whereas the opposite was true for IGF-1 (-36.8%). CONCLUSIONS: Taking into account the current understanding of the plausible biological role of the examined endocrine factors, those likely to be involved in the intrauterine origin of breast cancer are SHBG and IGF-2, with higher cord blood levels among Chinese, and IGF-1, with higher cord blood levels among Caucasian women.

Dietary fat intake in the European Prospective Investigation into Cancer and Nutrition: results from the 24-h dietary recalls.

OBJECTIVES: This paper describes the dietary intake of total fat, saturated (SFA), monounsaturated (MUFA) and polyunsaturated fatty acids (PUFA) and cholesterol of participants in the European Prospective Investigation into Cancer and Nutrition (EPIC) in 27 centres across 10 countries. METHODS: Between 1995 and 2000, a stratified random sample of 36 034 participants (age range 35-74 years) completed a standardized 24-h dietary recall, assessed by means of the computer software EPIC-SOFT. Lipid intake data were calculated using a standardized nutrient database. RESULTS: On average, the contribution of fat to total energy intake was >or=34% of energy intake (%en) in women and >or=36%en in men for most EPIC centres, except for the British, Dutch and most Italian cohorts. Total fat (>40%en) and MUFA intakes (21%en, mainly from olive oil) were highest in Greece. Except for the Greek, Spanish and Italian centres, the average MUFA intake ranged between 10 and 13%en, with a high proportion derived from animal sources. SFA intake in women and men was lowest in the Greek, Spanish, Italian and UK cohorts with an average of

Glycemic load in relation to hepatocellular carcinoma among patients with chronic hepatitis infection.

BACKGROUND: Chronic infections with hepatitis B virus (HBV) and hepatitis C virus (HCV) are of paramount etiologic importance for hepatocellular carcinoma (HCC), but other factors are likely to be important. The association of diabetes mellitus and obesity with HCC raises the possibility that dietary glycemic load (GL) may interact with chronic hepatitis infection in the causation of HCC. PATIENTS AND METHODS: We conducted a case-control study of 333 HCC patients and 360 controls in Athens, Greece. Third-generation assays were used to determine chronic HBV and HCV infection and information from a semiquantitative food frequency questionnaire to estimate dietary GL. RESULTS: After adjustment for possible confounding factors through multiple logistic regression, we found a nonsignificant positive association between GL and HCC, which was exclusively accounted for by a positive association between GL and HCC cases with chronic infection with hepatitis B and/or C. For the latter group of patients, the odds ratio at the highest compared with the lowest GL quintile was 1.95 (95% confidence interval 1.09-3.48). The association was strengthened after exclusion of subjects with diabetes. CONCLUSION: Our results indicate that, among patients with chronic infection with HBV and/or HCV, reduction of dietary GL could reduce risk or delay development of HCC.