Genomic signature of parity in the breast of premenopausal women.

Background: Full-term pregnancy (FTP) at an early age confers long-term protection against breast cancer. Previously, we reported that a FTP imprints a specific gene expression profile in the breast of postmenopausal women. Herein, we evaluated gene expression changes induced by parity in the breast of premenopausal women.

Blood levels of cadmium and lead in relation to breast cancer risk in three prospective cohorts.

Cadmium and lead have been classified as carcinogens by the International Agency for Research on Cancer. However, their associations with breast cancer risk are unknown despite their persistence in the environment and ubiquitous human exposure. We examined associations of circulating levels of cadmium and lead with breast cancer risk in three case-control studies nested within the Cancer Prevention Study-II (CPS-II) LifeLink Cohort, European Prospective Investigation into Cancer and Nutrition - Italy (EPIC-Italy) and the Northern Sweden Health and Disease Study (NSHDS) cohorts.

Epigenome-wide association study of adiposity and future risk of obesity-related diseases.

Background: Obesity is an established risk factor for several common chronic diseases such as breast and colorectal cancer, metabolic and cardiovascular diseases; however, the biological basis for these relationships is not fully understood. To explore the association of obesity with these conditions, we investigated peripheral blood leucocyte (PBL) DNA methylation markers for adiposity and their contribution to risk of incident breast and colorectal cancer and myocardial infarction.

Methods: DNA methylation profiles (Illumina Infinium HumanMethylation450 BeadChip) from 1941 individuals from four population-based European cohorts were analysed in relation to body mass index, waist circumference, waist-hip and waist-height ratio within a meta-analytical framework.

Pre-diagnostic blood immune markers, incidence and progression of B-cell lymphoma and multiple myeloma: Univariate and functionally informed multivariate analyses.

Recent prospective studies have shown that dysregulation of the immune system may precede the development of B-cell lymphomas (BCL) in immunocompetent individuals. However, to date, the studies were restricted to a few immune markers, which were considered separately. Using a nested case-control study within two European prospective cohorts, we measured plasma levels of 28 immune markers in samples collected a median of 6 years before diagnosis (range 2.

Functional germline variants in driver genes of breast cancer.

Purpose: Germline mutations in tumour suppressor genes cause various cancers. These genes are also somatically mutated in sporadic tumours. We hypothesized that there may also be cancer-related germline variants in the genes commonly mutated in sporadic breast tumours.

Inbreeding and homozygosity in breast cancer survival.

Genome-wide association studies (GWASs) help to understand the effects of single nucleotide polymorphisms (SNPs) on breast cancer (BC) progression and survival. We performed multiple analyses on data from a previously conducted GWAS for the influence of individual SNPs, runs of homozygosity (ROHs) and inbreeding on BC survival. (I.

Genetic Polymorphisms in Vitamin D Metabolism and Signaling Genes and Risk of Breast Cancer: A Nested Case-Control Study.

Genetic polymorphisms in vitamin D metabolism and signaling genes have been inconsistently associated with risk of breast cancer, though few studies have examined SNPs in vitamin D-related genes other than the vitamin D receptor (VDR) gene and particularly have not examined the association with the retinoid X receptor alpha (RXRA) gene which may be a key vitamin D pathway gene. We conducted a nested case-control study of 734 cases and 1435 individually matched controls from a population-based prospective cohort study, the Northern Sweden Mammary Screening Cohort. Tag and functional SNPs were genotyped for the VDR, cytochrome p450 24A1 (CYP24A1), and RXRA genes.

Impact of functional germline variants and a deletion polymorphism in APOBEC3A and APOBEC3B on breast cancer risk and survival in a Swedish study population.

Purpose: The C → T mutation signature caused by APOBEC family members contributes to the development of breast cancer (BC). Also overexpression of APOBEC3B and a ~29.5-kb deletion polymorphism between APOBEC3A and APOBEC3B have been associated with increased BC risk.

Systematic pathway enrichment analysis of a genome-wide association study on breast cancer survival reveals an influence of genes involved in cell adhesion and calcium signaling on the patients' clinical outcome.

Genome-wide association studies (GWASs) may help to understand the effects of genetic polymorphisms on breast cancer (BC) progression and survival. However, they give only a focused view, which cannot capture the tremendous complexity of this disease. Therefore, we investigated data from a previously conducted GWAS on BC survival for enriched pathways by different enrichment analysis tools using the two main annotation databases Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG).

Circulating estrogen metabolites and risk of breast cancer in postmenopausal women.

Background: It has been hypothesized that predominance of the 2-hydroxylation estrogen metabolism pathway over the 16α-hydroxylation pathway may be inversely associated with breast cancer risk.

Methods: We examined the associations of invasive breast cancer risk with circulating 2-hydroxyestrone (2-OHE1), 16α-hydroxyestrone (16α-OHE1), and the 2-OHE1:16α-OHE1 ratio in a case-control study of postmenopausal women nested within two prospective cohorts: the New York University Women's Health Study (NYUWHS) and the Northern Sweden Mammary Screening Cohort (NSMSC), with adjustment for circulating levels of estrone, and additional analyses by tumor estrogen receptor (ER) status. Levels of 2-OHE1 and 16α-OHE1 were measured using ESTRAMET 2/16 assay in stored serum or plasma samples from 499 incident breast cancer cases and 499 controls, who were matched on cohort, age, and date of blood donation.

Genetic variants in hormone-related genes and risk of breast cancer.

Sex hormones play a key role in the development of breast cancer. Certain polymorphic variants (SNPs and repeat polymorphisms) in hormone-related genes are associated with sex hormone levels. However, the relationship observed between these genetic variants and breast cancer risk has been inconsistent.

Low-carbohydrate, high-protein diet score and risk of incident cancer; a prospective cohort study.

Background: Although carbohydrate reduction of varying degrees is a popular and controversial dietary trend, potential long-term effects for health, and cancer in specific, are largely unknown.

Methods: We studied a previously established low-carbohydrate, high-protein (LCHP) score in relation to the incidence of cancer and specific cancer types in a population-based cohort in northern Sweden. Participants were 62,582 men and women with up to 17.

Circulating levels of 25-hydroxyvitamin D and risk of breast cancer: a nested case-control study.

Introduction: Experimental evidence suggests a protective role for circulating 25-hydroxyvitamin D (25(OH)D) in breast cancer development, but the results of epidemiological studies have been inconsistent.

Methods: We conducted a case-control study nested within two prospective cohorts, the New York University Women's Health Study and the Northern Sweden Mammary Screening Cohort. Blood samples were collected at enrollment, and women were followed up for breast cancer ascertainment.

Dietary intake of vitamin D and calcium and breast cancer risk in the European Prospective Investigation into Cancer and Nutrition.

Studies assessing the effects of vitamin D or calcium intake on breast cancer risk have been inconclusive. Furthermore, few studies have evaluated them jointly. This study is the largest so far examining the association of dietary vitamin D and calcium intake with breast cancer risk in the European Prospective Investigation into Cancer and Nutrition.

Dietary fiber intake and risk of hormonal receptor-defined breast cancer in the European Prospective Investigation into Cancer and Nutrition study.

Background: Limited scientific evidence has characterized the association between dietary fiber intake and risk of breast cancer (BC) by menopausal status and hormone receptor expression in tumors.

Objective: We investigated the relation between total dietary fiber and its main food sources (vegetables, fruit, cereals, and legumes) and BC risk by using data from the European Prospective Investigation into Cancer and Nutrition (EPIC).

Design: A total of 11,576 invasive BC cases in 334,849 EPIC women mostly aged 35-70 y at baseline were identified over a median follow-up of 11.

Defining the genomic signature of the parous breast.

Background: It is accepted that a woman's lifetime risk of developing breast cancer after menopause is reduced by early full term pregnancy and multiparity. This phenomenon is thought to be associated with the development and differentiation of the breast during pregnancy.

Methods: In order to understand the underlying molecular mechanisms of pregnancy induced breast cancer protection, we profiled and compared the transcriptomes of normal breast tissue biopsies from 71 parous (P) and 42 nulliparous (NP) healthy postmenopausal women using Affymetrix Human Genome U133 Plus 2.

Prediction of breast cancer risk by genetic risk factors, overall and by hormone receptor status.

Objective: There is increasing interest in adding common genetic variants identified through genome wide association studies (GWAS) to breast cancer risk prediction models. First results from such models showed modest benefits in terms of risk discrimination. Heterogeneity of breast cancer as defined by hormone-receptor status has not been considered in this context.

Interactive effect of genetic susceptibility with height, body mass index, and hormone replacement therapy on the risk of breast cancer.

Background: Breast cancer today has many established risk factors, both genetic and environmental, but these risk factors by themselves explain only part of the total cancer incidence. We have investigated potential interactions between certain known genetic and phenotypic risk factors, specifically nine single nucleotide polymorphisms (SNPs) and height, body mass index (BMI) and hormone replacement therapy (HRT).

Methods: We analyzed samples from three different study populations: two prospectively followed Swedish cohorts and one Icelandic case-control study.

Methylation signature of lymph node metastases in breast cancer patients.

Background: Invasion and metastasis are two important hallmarks of malignant tumors caused by complex genetic and epigenetic alterations. The present study investigated the contribution of aberrant methylation profiles of cancer related genes, APC, BIN1, BMP6, BRCA1, CST6, ESR-b, GSTP1, P14 (ARF), P16 (CDKN2A), P21 (CDKN1A), PTEN, and TIMP3, in the matched axillary lymph node metastasis in comparison to the primary tumor tissue and the adjacent normal tissue from the same breast cancer patients to identify the potential of candidate genes methylation as metastatic markers.

Methods: The quantitative methylation analysis was performed using the SEQUENOM's EpiTYPER™ assay which relies on matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS).

Selected polymorphisms in sex hormone-related genes, circulating sex hormones and risk of endometrial cancer.

Background: The role of estrogen and progesterone in the development of endometrial cancer is well documented. Few studies have examined the association of genetic variants in sex hormone-related genes with endometrial cancer risk.

Methods: We conducted a case-control study nested within three cohorts to examine the association of endometrial cancer risk with polymorphisms in hormone-related genes among 391 cases (92% postmenopausal at diagnosis) and 712 individually-matched controls.

A traditional Sami diet score as a determinant of mortality in a general northern Swedish population.

Objectives: To examine the relationship between "traditional Sami" dietary pattern and mortality in a general northern Swedish population.

Study Design: Population-based cohort study.

Methods: We examined 77,319 subjects from the Västerbotten Intervention Program (VIP) cohort.

Adiposity, hormone replacement therapy use and breast cancer risk by age and hormone receptor status: a large prospective cohort study.

Introduction: Associations of hormone-receptor positive breast cancer with excess adiposity are reasonably well characterized; however, uncertainty remains regarding the association of body mass index (BMI) with hormone-receptor negative malignancies, and possible interactions by hormone replacement therapy (HRT) use.

Methods: Within the European EPIC cohort, Cox proportional hazards models were used to describe the relationship of BMI, waist and hip circumferences with risk of estrogen-receptor (ER) negative and progesterone-receptor (PR) negative (n = 1,021) and ER+PR+ (n = 3,586) breast tumors within five-year age bands. Among postmenopausal women, the joint effects of BMI and HRT use were analyzed.

Low-carbohydrate, high-protein score and mortality in a northern Swedish population-based cohort.

Background/objective: Long-term effects of carbohydrate-restricted diets are unclear. We examined a low-carbohydrate, high-protein (LCHP) score in relation to mortality.

Subjects/methods: This is a population-based cohort study on adults in the northern Swedish county of Västerbotten.

Mutations of mitochondrial DNA as potential biomarkers in breast cancer.

Background: Alterations of mitochondrial DNA (mtDNA) have been found in cancer patients, therefore informative mtDNA mutations could serve as biomarkers for the disease.

Materials And Methods: The two hypervariable regions HVR1 and HVR2 in the D-Loop region were sequenced in ten paired tissue and plasma samples from breast cancer patients.

Results: MtDNA mutations were found in all patients' samples, suggesting a 100% detection rate.

Combined effect of low-penetrant SNPs on breast cancer risk.

Background: Although many low-penetrant genetic risk factors for breast cancer have been discovered, knowledge about the effect of multiple risk alleles is limited, especially in women <50 years. We therefore investigated the association between multiple risk alleles and breast cancer risk as well as individual effects according to age-approximated pre- and post-menopausal status.

Methods: Ten previously described breast cancer-associated single-nucleotide polymorphisms (SNPs) were analysed in a joint European biobank-based study comprising 3584 breast cancer cases and 5063 cancer-free controls.