Cumulative genetic defects in carcinogen metabolism may increase breast cancer risk (The Netherlands).

Variants in the metabolic genes NAT1, NAT2, GSTM1 or GSTT1, may cause differences in individual detoxifying capacity of possible carcinogens. We examined the cumulative effect of putative at risk genotypes on breast cancer risk and we examined the extent to which these polymorphisms modify the association between smoking and breast cancer. A case cohort study was conducted in the DOM cohort with 676 breast cancer cases and a random sample of 669 individuals.

Serum sex steroids in premenopausal women and breast cancer risk within the European Prospective Investigation into Cancer and Nutrition (EPIC).

Background: Contrasting etiologic hypotheses about the role of endogenous sex steroids in breast cancer development among premenopausal women implicate ovarian androgen excess and progesterone deficiency, estrogen excess, estrogen and progesterone excess, and both an excess or lack of adrenal androgens (dehydroepiandrosterone [DHEA] or its sulfate [DHEAS]) as risk factors. We conducted a case-control study nested within the European Prospective Investigation into Cancer and Nutrition cohort to examine associations among premenopausal serum concentrations of sex steroids and subsequent breast cancer risk.

Methods: Levels of DHEAS, (Delta4-)androstenedione, testosterone, and sex hormone binding globulin (SHBG) were measured in single prediagnostic serum samples from 370 premenopausal women who subsequently developed breast cancer (case patients) and from 726 matched cancer-free control subjects.

Cyp17, urinary sex steroid levels and breast cancer risk in postmenopausal women.

Endogenous sex hormones play an important role in the etiology of breast cancer. Polymorphisms in genes encoding for enzymes involved in steroidogenesis may therefore play a role in breast cancer risk. Cytochrome P450c17alpha (Cyp17) functions at key branch points in human steroidogenesis.

Postmenopausal breast cancer risk and cumulative number of menstrual cycles.

Objective: To explore whether the lifetime cumulative number of menstrual cycles, as an index for total exposure to endogenous estrogens, and the number of menstrual cycles until a first full-term pregnancy (FFTP), are associated with breast cancer risk in postmenopausal women.

Methods: Population-based study with data from the Prospect-European Prospective Investigation into Cancer and Nutrition study. Naturally menopausal participants were eligible (n = 6,718).

Consumption of vegetables and fruits and risk of breast cancer.

Context: The intake of vegetables and fruits has been thought to protect against breast cancer. Most of the evidence comes from case-control studies, but a recent pooled analysis of the relatively few published cohort studies suggests no significantly reduced breast cancer risk is associated with vegetable and fruit consumption.

Objective: To examine the relation between total and specific vegetable and fruit intake and the incidence of breast cancer.

Alcohol and endogenous sex steroid levels in postmenopausal women: a cross-sectional study.

Breast cancer risk increases with increased levels of alcohol consumption, potentially through an effect on sex hormone levels. In a cross-sectional study among Dutch participants (n = 17,357) of the European Prospective Investigation into Cancer and Nutrition conducted in Utrecht, The Netherlands (Prospect-EPIC), we investigated the relation between alcohol intake and estrogen and androgen levels. Alcohol intake was calculated from a food frequency questionnaire.

No association of estrogen receptor alpha and cytochrome P450c17alpha polymorphisms with age at menopause in a Dutch cohort.

Background: Age at menopause is under strong genetic control. So far, genetic variations of only one gene, the PvuII polymorphism of the estrogen receptor alpha (ERalpha) gene, have been shown to be associated with age at onset of menopause. This study aims to investigate whether PvuII, XbaI and B-variant polymorphisms of the ERalpha gene, and the MspAI polymorphism of the cytochrome P450c17alpha (CYP17) gene are associated with age at menopause in a Dutch cohort.

Dietary determinants of circulating insulin-like growth factor (IGF)-I and IGF binding proteins 1, -2 and -3 in women in the Netherlands.

Objective: Epidemiological studies suggest that individuals with elevated plasma concentrations of insulin-like growth factor (IGF-I) are at increased risk of developing cancer. We assessed whether dietary intake of total energy, protein, alcohol, phytoestrogens and related foods, and tomatoes and lycopene was associated with plasma levels of IGF-I and IGF binding proteins (IGFBPs) in Dutch women.

Methods: A cross-sectional study was conducted in 224 premenopausal and 162 postmenopausal women, aged 49-69, participating in the Prospect-EPIC study in the Netherlands.

Body size and breast cancer risk: findings from the European Prospective Investigation into Cancer And Nutrition (EPIC).

The evidence for anthropometric factors influencing breast cancer risk is accumulating, but uncertainties remain concerning the role of fat distribution and potential effect modifiers. We used data from 73,542 premenopausal and 103,344 postmenopausal women from 9 European countries, taking part in the EPIC study. RRs from Cox regression models were calculated, using measured height, weight, BMI and waist and hip circumferences; categorized by cohort-wide quintiles; and expressed as continuous variables, adjusted for study center, age and other risk factors.

Long term consequences of the 1944-1945 Dutch famine on the insulin-like growth factor axis.

The insulin-like growth factor axis is highly responsive to nutritional status and may be involved as one of the underlying mechanisms through which caloric restriction could affect cancer risk. High levels of circulating insulin-like growth factor (IGF)-I, or IGF-I relative to IGF binding protein (IGFBP)-3 have been related to various human cancer types. In a group of 87 postmenopausal women, we found that childhood exposure to the 1944-1945 Dutch famine was associated with increased plasma levels of IGF-I and IGFBP-3, whereas IGFBP-1 and -2 levels were weakly decreased.

The V89L polymorphism in the 5-alpha-reductase type 2 gene and risk of breast cancer.

Women with high androgen levels appear to be at increased risk for breast cancer. The 5-alpha-reductase type 2 enzyme (SRD5A2) is an important mediator of local androgen actions. The SRD5A2 gene contains a polymorphism leading to a valine to leucine change in codon 89 (V89L).

Heterozygosity for the Cys282Tyr mutation in the HFE gene and the risk of colorectal cancer (Netherlands).

Background & Aims: Heterozygosity for the Cys282Tyr transition in the HFE-gene is associated with slightly increased iron levels and may therefore be a potential risk factor for colorectal cancer.

Methods: We studied the relationship between Cys282Tyr-heterozygosity and colorectal cancer using a case-control design. The 240 colorectal cancer cases and 635 controls in our study were derived from a prospective cohort study of 12,242 postmenopausal women, who were invited for an experimental breast cancer screening program in Utrecht, The Netherlands.

Circulating levels of insulin-like growth factor I, its binding proteins -1,-2, -3, C-peptide and risk of postmenopausal breast cancer.

Higher levels of circulating Insulin-like Growth Factor (IGF)-I may be associated with higher risks for premenopausal breast cancer. We investigate the associations between circulating levels of IGF-I, its binding proteins (IGFBPs) -1, -2, -3, C-peptide and postmenopausal breast cancer. This is a prospective study nested in 2 Dutch cohorts.

Differences in base excision repair capacity may modulate the effect of dietary antioxidant intake on prostate cancer risk: an example of polymorphisms in the XRCC1 gene.

We propose a hypothesis that differences in base excision repair capacity modulate the effect of dietary antioxidant intake on prostate cancer risk. As a preliminary test of this hypothesis, we conducted a pilot case-control study to evaluate prostate cancer risk in men with polymorphisms in the XRCC1 gene, a key player in base excision repair, across different strata of antioxidant intake. Seventy-seven prostate cancer patients and 183 community controls, for whom we have detailed dietary information, were frequency matched on age and race.

HRAS1 variable number of tandem repeats polymorphism and risk of bladder cancer.

The HRAS1 variable number of tandem repeats (VNTR) polymorphism, 1 kb downstream from the HRAS1 gene, has been reported to be associated with risk of various cancers. To examine whether individuals with rare HRAS1 VNTR alleles are at increased risk of bladder cancer we carried out a case control study with 230 bladder cancer cases and 203 hospital-based controls frequency-matched on ethnicity, gender and age. For genotyping we used a PCR-based long-gel electrophoretic assay that provides precise allele size discrimination.