Polycystic ovarian syndrome (PCOS), related symptoms/sequelae, and breast cancer risk in a population-based case-control study.

Purpose: Despite the overlap between the clinical symptoms/sequelae of polycystic ovarian syndrome (PCOS) and many known reproductive risk factors for breast cancer, the relationship between PCOS and breast cancer remains unclear, possibly because of the complex heterogeneity and challenges in diagnosing PCOS over time. We hypothesized that PCOS, specific PCOS-related symptoms/sequelae, or clusters of PCOS-related symptoms/sequelae may be differentially associated with pre- versus postmenopausal breast cancer risk.

Materials And Methods: Cases were 1,508 women newly diagnosed with a first primary in situ or invasive breast, and the 1,556 population-based controls were frequency-matched by age.

Genetic variants associated with breast cancer risk for Ashkenazi Jewish women with strong family histories but no identifiable BRCA1/2 mutation.

The ability to establish genetic risk models is critical for early identification and optimal treatment of breast cancer. For such a model to gain clinical utility, more variants must be identified beyond those discovered in previous genome-wide association studies (GWAS). This is especially true for women at high risk because of family history, but without BRCA1/2 mutations.

Genetic variation in telomere maintenance genes, telomere length and breast cancer risk.

Background: Telomeres at the ends of eukaryotic chromosomes play a critical role in maintaining the integrity and stability of the genome and participate in the initiation of DNA damage/repair responses.

Methods: We performed a case-control study to evaluate the role of three SNPs (TERT-07, TERT-54 and POT1-03) in telomere maintenance genes previously found to be significantly associated with breast cancer risk. We used sister-sets obtained from the New York site of the Breast Cancer Family Registry (BCFR).

Contribution of large genomic BRCA1 alterations to early-onset breast cancer selected for family history and tumour morphology: a report from The Breast Cancer Family Registry.

Introduction: Selecting women affected with breast cancer who are most likely to carry a germline mutation in BRCA1 and applying the most appropriate test methodology remains challenging for cancer genetics services. We sought to test the value of selecting women for BRCA1 mutation testing on the basis of family history and/or breast tumour morphology criteria as well as the value of testing for large genomic alterations in BRCA1.

Methods: We studied women participating in the Breast Cancer Family Registry (BCFR), recruited via population-based sampling, who had been diagnosed with breast cancer before the age of 40 years who had a strong family history of breast or ovarian cancer (n = 187) and/or a first primary breast tumour with morphological features consistent with carrying a BRCA1 germline mutation (n = 133; 37 met both criteria).

Is pregnancy after breast cancer safe?

The impact of treatment on subsequent fertility and the safety of childbearing are major complicating factors for young women diagnosed with breast cancer. As national data indicate women are postponing first pregnancy to older ages; therefore, many young patients are seeking clinical guidance regarding the safety of conception and treatment options that may not prevent subsequent pregnancy. Newly developed chemotherapy protocols of brief duration have improved life expectancy enabling some women to consider childbearing.

Investigation of the miR16-1 (C > T) + 7 Substitution in Seven Different Types of Cancer from Three Ethnic Groups.

Background. MicroRNAs are a type of small noncoding RNA molecules that have been shown to control gene expression in eukaryotes. Aberrant expression and alteration of miRNAs may be responsible for human diseases including cancer.

Aberrant methylation of RASSF1A in plasma DNA before breast cancer diagnosis in the Breast Cancer Family Registry.

In addition to classic genetic mechanisms such as deletions and mutations, growth regulatory genes can be inactivated via methylation of cytosine-residues in their promoter regions. Hypermethylation of promoter CpG islands is now recognized as an important and early event in carcinogenesis. Detection of methylated DNA in serum or plasma has been suggested to be a marker for early cancer development.

Prediction of BRCA Mutations Using the BRCAPRO Model in Clinic-Based African American, Hispanic, and Other Minority Families in the United States.

Purpose: BRCAPRO, a BRCA mutation carrier prediction model, was developed on the basis of studies in individuals of Ashkenazi Jewish and European ancestry. We evaluated the performance of the BRCAPRO model among clinic-based minority families. We also assessed the clinical utility of mutation status of probands (the first individual tested in a family) in the recommendation of BRCA mutation testing for other at-risk family members.

Do placental genes affect maternal breast cancer? Association between offspring's CGB5 and CSH1 gene variants and maternal breast cancer risk.

The protective effect of full-term pregnancy against breast cancer is thought to be induced by two placental hormones: human chorionic gonadotropin and human chorionic somatotropin hormone (CSH) produced by the placental trophoblastic cells. We hypothesized that variants in placental genes encoding these hormones may alter maternal breast cancer risk subsequent to pregnancy. We conducted a case-control study to examine the association between polymorphisms in a woman's placental (i.

BRCA1 and BRCA2 mutation carriers in the Breast Cancer Family Registry: an open resource for collaborative research.

The Breast Cancer Family Registry is a resource for interdisciplinary and translational studies of the genetic epidemiology of breast cancer. This resource is available to researchers worldwide for collaborative studies. Herein, we report the results of testing for germline mutations in BRCA1 and BRCA2.

Double-strand breaks repair in lymphoblastoid cell lines from sisters discordant for breast cancer from the New York site of the BCFR.

Unrepaired DNA double-strand breaks (DSBs) may have serious consequences for cells by inducing chromosomal aberrations, thereby increasing genetic instability and cancer risk. One's capacity to repair DSB is therefore an important factor to consider when estimating cancer risk. We assessed DNA end-joining (EJ) capacity in cell lines derived from sisters discordant for breast cancer to determine if individual differences in DSB repair are a significant risk factor.

Cancer screening practices of Asian American physicians in New York City.

Cancer screening rates are lower among Asian Americans than the general USA population. While prior studies examined characteristics of Asian American patients as predictors of cancer screening, few investigated their health care providers. Asian American primary care physicians practicing in New York City were surveyed by questionnaire regarding their demographics, practice characteristics, and cancer screening of their Asian American patients.

Short telomere length and breast cancer risk: a study in sister sets.

Telomeres consist of a tandem repeats of the sequence TTAGGG at the ends of chromosomes and play a key role in the maintenance of chromosomal stability. Previous studies indicated that short telomeres are associated with increased risk for human bladder, head and neck, lung, and renal cell cancer. We investigated the association between white blood cell telomere length and breast cancer risk among 268 family sets (287 breast cancer cases and 350 sister controls).

Alcohol metabolism, alcohol intake, and breast cancer risk: a sister-set analysis using the Breast Cancer Family Registry.

Moderate alcohol intake has been consistently associated with a modest (30-50%) increase in breast cancer risk, but it remains unclear if certain individuals have higher susceptibility to the harmful effects of alcohol intake. 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. Using data from the Breast Cancer Family Registry (n = 811 sister sets), we examined whether sisters with breast cancer differ with respect to alcohol consumption and alcohol metabolism (measured by polymorphisms in ADH1B and ADH1C) compared to their sisters without breast cancer.

BRCA1 and BRCA2 mutation carriers, oral contraceptive use, and breast cancer before age 50.

Background: Understanding the effect of oral contraceptives on risk of breast cancer in BRCA1 or BRCA2 mutation carriers is important because oral contraceptive use is a common, modifiable practice.

Methods: We studied 497 BRCA1 and 307 BRCA2 mutation carriers, of whom 195 and 128, respectively, had been diagnosed with breast cancer. Case-control analyses were conducted using unconditional logistic regression with adjustments for family history and familial relationships and were restricted to subjects with a reference age under 50 years.

Polymorphisms in nucleotide excision repair genes and DNA repair capacity phenotype in sisters discordant for breast cancer.

Interindividual differences in DNA repair capacity (DRC) may play a critical role in breast cancer risk. Previously, we determined that DRC measured via removal of in vitro-induced benzo[a]pyrene diolepoxide-DNA adducts in lymphoblastoid cell lines was lower in cases compared with controls among sisters discordant for breast cancer from the Metropolitan New York Registry of Breast Cancer Families. We have now determined genotypes for seven single nucleotide polymorphisms in five nucleotide excision repair genes, including Xeroderma pigmentosum complementation group A (XPA +62T>C), group C (XPC Lys939Gln and Ala499Val), group D (XPD Asp312Asn and Lys751Gln), and group G (XPG His1104Asp) and ERCC1 (8092 C>A) in a total of 160 sister pairs for whom DRC phenotype data were available.

Variants in estrogen metabolism and biosynthesis genes and urinary estrogen metabolites in women with a family history of breast cancer.

We examined associations between polymorphisms in genes related to estrogen metabolism (CYP1B1 codon 432G --> C rs#1056836, CYP1B1 codon 453A --> G rs#1800440, COMT codon 158G --> A rs#4680) and biosynthesis (CYP17 T --> C promoter rs#743572, CYP19 exon 4 TTTA repeat) and urinary estrogen metabolites (2-hydroxyestrogens (2-OHE), 16alpha-hydroxyestrone (16alpha-OHE1), and their ratio) in a pilot study of 64 pre- and post-menopausal women with a family history of breast cancer. Women were participants in the Metropolitan New York Registry of Breast Cancer Families, one of six international sites of the National Cancer Institute's Breast Cancer Family Registry. We used linear regression to examine the effects of genetic variants on log-transformed urinary estrogen metabolites.

New York AANCART: using participatory research to address the health needs of South Asian and Korean Americans in New York City.

Since its inception in April 2000, the New York Asian American Network for Cancer Awareness, Research, and Training (NY AANCART) has conducted cancer control education, research, and infrastructure-building activities in collaboration with the agenda of the national AANCART project, one of the Special Population Networks funded by the National Cancer Institute. In New York, the AANCART program was developed based on the principles of community-based participatory research (CBPR), a research approach that is centered on community strengths and issues and that engages the community in the research process. NY AANCART has been dedicated to developing leadership within and collaboration with community-based organizations (CBOs) to address the needs of medically underserved New York Asian-American populations.

DNA repair capacity of lymphoblastoid cell lines from sisters discordant for breast cancer.

Background: Interindividual differences in DNA repair capacity may influence cancer risk. We tested whether the nucleotide excision repair pathway was deficient in breast cancer case patients by analyzing sister pairs.

Methods: Cell lines derived from sisters discordant for breast cancer (137 families containing 158 case patients and 154 control sisters) were obtained from the Metropolitan New York Registry of Breast Cancer Families.

Variants in estrogen-biosynthesis genes CYP17 and CYP19 and breast cancer risk: a family-based genetic association study.

Background: Case-control studies have reported inconsistent results concerning breast cancer risk and polymorphisms in genes that control endogenous estrogen biosynthesis. We report findings from the first family-based association study examining associations between female breast cancer risk and polymorphisms in two key estrogen-biosynthesis genes CYP17 (T-->C promoter polymorphism) and CYP19 (TTTA repeat polymorphism).

Methods: We conducted the study among 278 nuclear families containing one or more daughters with breast cancer, with a total of 1123 family members (702 with available constitutional DNA and questionnaire data and 421 without them).

The Breast Cancer Family Registry: an infrastructure for cooperative multinational, interdisciplinary and translational studies of the genetic epidemiology of breast cancer.

Introduction: The etiology of familial breast cancer is complex and involves genetic and environmental factors such as hormonal and lifestyle factors. Understanding familial aggregation is a key to understanding the causes of breast cancer and to facilitating the development of effective prevention and therapy. To address urgent research questions and to expedite the translation of research results to the clinical setting, the National Cancer Institute (USA) supported in 1995 the establishment of a novel research infrastructure, the Breast Cancer Family Registry, a collaboration of six academic and research institutions and their medical affiliates in the USA, Canada, and Australia.

A family-based genetic association study of variants in estrogen-metabolism genes COMT and CYP1B1 and breast cancer risk.

In this paper, we report findings from a family-based association study examining the association between polymorphisms in two key estrogen-metabolism genes CYP1B1 (codon 432 G --> C and codon 453 A --> G variants) and COMT (codon 158 G --> A variant) and female breast cancer. We conducted the study among 280 nuclear families containing one or more daughters with breast cancer with a total of 1124 family members (702 with available constitutional DNA and questionnaire data and 421 without). These nuclear families were selected from breast cancer families participating in the Metropolitan New York Registry (MNYR) - one of the six centers of NCI's Breast Cooperative Family Registry.

The Long Island Breast Cancer Study Project: description of a multi-institutional collaboration to identify environmental risk factors for breast cancer.

The Long Island Breast Cancer Study Project is a federally mandated, population-based case-control study to determine whether breast cancer risk among women in the counties of Nassau and Suffolk, NY, is associated with selected environmental exposures, assessed by blood samples, self-reports, and environmental home samples. This report describes the collaborative project's background, rationale, methods, participation rates, and distributions of known risk factors for breast cancer by case-control status, by blood donation, and by availability of environmental home samples. Interview response rates among eligible cases and controls were 82.

Removal of benzo(a)pyrene diol epoxide (BPDE)-DNA adducts as a measure of DNA repair capacity in lymphoblastoid cell lines from sisters discordant for breast cancer.

The mutagen sensitivity assay is one of the approaches used to investigate individual DNA repair capacity. This method is based on the premise that after in vitro treatment with a test mutagen, DNA from subjects with defective repair will be more damaged than DNA from those with an efficient repair system. However, very little is known about unmeasured processes that occur between cell treatment and final assessment of DNA damage.