Association between adult height, genetic susceptibility and risk of glioma.

Background: Some, but not all, observational studies have suggested that taller stature is associated with a significant increased risk of glioma. In a pooled analysis of observational studies, we investigated the strength and consistency of this association, overall and for major sub-types, and investigated effect modification by genetic susceptibility to the disease.

Methods: We standardized and combined individual-level data on 1354 cases and 4734 control subjects from 13 prospective and 2 case-control studies.

Use of aspirin, other nonsteroidal anti-inflammatory drugs, and acetaminophen and postmenopausal breast cancer incidence.

Purpose: The associations between use of aspirin, other nonsteroidal anti-inflammatory drugs (NSAIDs), and acetaminophen and breast cancer incidence in postmenopausal women are uncertain. We examined these associations with breast cancer, both overall and by molecular subtype.

Patients And Methods: We observed 84,602 postmenopausal women, free of cancer in 1980, until June 2008 and prospectively collected data on analgesic use, reproductive history, and other lifestyle factors using biennial questionnaires.

Genetic variability in IGF-1 and IGFBP-3 and body size in early life.

Background: Early life body size and circulating levels of IGF-1 and IGFBP-3 have been linked to increased risks of breast and other cancers, but it is unclear whether these exposures act through a common mechanism. Previous studies have examined the role of IGF-1 and IGFBP-3 genetic variation in relation to adult height and body size, but few studies have examined associations with birthweight and childhood size.

Methods: We examined whether htSNPs in IGF-1 and the IGFBP-1/IGFBP-3 gene region are associated with the self-reported outcomes of birthweight, body fatness at ages 5 and 10, and body mass index (BMI) at age 18 among healthy women from the Nurses' Health Study (NHS) and NHSII.

Association between physical activity and urinary estrogens and estrogen metabolites in premenopausal women.

Objective: The objective of the study was to evaluate in premenopausal women the relationships of physically active and sedentary behaviors reported for adulthood and adolescence with a comprehensive profile of estrogen metabolism.

Methodology: Fifteen estrogens and estrogen metabolites (jointly termed EM) were measured using liquid chromatography-tandem mass spectrometry in luteal phase urines from 603 premenopausal women in the Nurses' Health Study II. Geometric means of individual EM, metabolic pathway groups, and pathway ratios were examined by level of exposure after adjustment for age, body mass index, alcohol intake, menstrual cycle length, and sample collection timing.

Age at last birth in relation to risk of endometrial cancer: pooled analysis in the epidemiology of endometrial cancer consortium.

Childbearing at an older age has been associated with a lower risk of endometrial cancer, but whether the association is independent of the number of births or other factors remains unclear. Individual-level data from 4 cohort and 13 case-control studies in the Epidemiology of Endometrial Cancer Consortium were pooled. A total of 8,671 cases of endometrial cancer and 16,562 controls were included in the analysis.

A genome-wide association meta-analysis of circulating sex hormone-binding globulin reveals multiple Loci implicated in sex steroid hormone regulation.

Sex hormone-binding globulin (SHBG) is a glycoprotein responsible for the transport and biologic availability of sex steroid hormones, primarily testosterone and estradiol. SHBG has been associated with chronic diseases including type 2 diabetes (T2D) and with hormone-sensitive cancers such as breast and prostate cancer. We performed a genome-wide association study (GWAS) meta-analysis of 21,791 individuals from 10 epidemiologic studies and validated these findings in 7,046 individuals in an additional six studies.

Duarte galactose-1-phosphate uridyl transferase genotypes are not associated with ovarian cancer risk.

Objective: To investigate whether galactose-1-phosphate uridyl transferase (GALT) variant genotypes were associated with epithelial ovarian cancer risk, and to determine if this association was modified by lactose intake.

Design: Two prospective cohort studies and a case-control study.

Setting: Academic institution.

Genome-wide association study of circulating estradiol, testosterone, and sex hormone-binding globulin in postmenopausal women.

Genome-wide association studies (GWAS) have successfully identified common genetic variants that contribute to breast cancer risk. Discovering additional variants has become difficult, as power to detect variants of weaker effect with present sample sizes is limited. An alternative approach is to look for variants associated with quantitative traits that in turn affect disease risk.

Detectable clonal mosaicism and its relationship to aging and cancer.

In an analysis of 31,717 cancer cases and 26,136 cancer-free controls from 13 genome-wide association studies, we observed large chromosomal abnormalities in a subset of clones in DNA obtained from blood or buccal samples. We observed mosaic abnormalities, either aneuploidy or copy-neutral loss of heterozygosity, of >2 Mb in size in autosomes of 517 individuals (0.89%), with abnormal cell proportions of between 7% and 95%.

Identification of a novel percent mammographic density locus at 12q24.

Percent mammographic density adjusted for age and body mass index (BMI) is one of the strongest risk factors for breast cancer and has a heritable component that remains largely unidentified. We performed a three-stage genome-wide association study (GWAS) of percent mammographic density to identify novel genetic loci associated with this trait. In stage 1, we combined three GWASs of percent density comprised of 1241 women from studies at the Mayo Clinic and identified the top 48 loci (99 single nucleotide polymorphisms).

Pathway analysis of genome-wide association study data highlights pancreatic development genes as susceptibility factors for pancreatic cancer.

Four loci have been associated with pancreatic cancer through genome-wide association studies (GWAS). Pathway-based analysis of GWAS data is a complementary approach to identify groups of genes or biological pathways enriched with disease-associated single-nucleotide polymorphisms (SNPs) whose individual effect sizes may be too small to be detected by standard single-locus methods. We used the adaptive rank truncated product method in a pathway-based analysis of GWAS data from 3851 pancreatic cancer cases and 3934 control participants pooled from 12 cohort studies and 8 case-control studies (PanScan).

Circadian genes and breast cancer susceptibility in rotating shift workers.

Rotating night shift work is associated with increased risk of breast cancer, likely via circadian disruption. We hypothesized that circadian pathway genes influence breast cancer risk, particularly in rotating night shift workers. We selected 178 common variants across 15 genes pertinent to the circadian system.

Common breast cancer susceptibility variants in LSP1 and RAD51L1 are associated with mammographic density measures that predict breast cancer risk.

Background: Mammographic density adjusted for age and body mass index (BMI) is a heritable marker of breast cancer susceptibility. Little is known about the biologic mechanisms underlying the association between mammographic density and breast cancer risk. We examined whether common low-penetrance breast cancer susceptibility variants contribute to interindividual differences in mammographic density measures.

Association between reproductive factors and urinary estrogens and estrogen metabolites in premenopausal women.

Background: Little is known about relationships among reproductive factors, estrogens and estrogen metabolites (jointly referred to as EM), and estrogen metabolism patterns.

Methods: In a cross-sectional analysis, we examined the associations of age at menarche, menstrual cycle length and regularity, parity, age at first and last birth, breastfeeding, and duration of and time since use of oral contraceptives with mid-luteal phase urinary EM in a sample of 603 premenopausal women, ages 33 to 51 years, within the Nurses' Health Study II (NHSII). Fifteen individual urinary EMs were measured with liquid chromatography/tandem mass spectrometry (LC/MS-MS) and analyzed both individually and in metabolic pathways.

Reproductive aging-associated common genetic variants and the risk of breast cancer.

Introduction: A younger age at menarche and an older age at menopause are well established risk factors for breast cancer. Recent genome-wide association studies have identified several novel genetic loci associated with these two traits. However, the association between these loci and breast cancer risk is unknown.

Insulin-like growth factor-1, insulin-like growth factor binding protein-3 and lobule type in the Nurses' Health Study II.

Introduction: Previous research in the Nurses' Health Study (NHS) and the NHSII observed that, among women diagnosed with benign breast disease (BBD), those with predominant type 1/no type 3 lobules (a marker of complete involution) versus other lobule types were at lower risk of subsequent breast cancer. Studies in animal models suggest that insulin-like growth factor-1 (IGF-1) may inhibit involution of lobules in the breast; however, this has not been studied in humans.

Methods: We conducted a cross-sectional study among 472 women in the NHSII who were diagnosed with biopsy-confirmed proliferative BBD between 1991 and 2002 and provided blood samples between 1996 and 1999.

Family history and risk of breast cancer: nurses' health study.

Family history of cancer remains underused in general clinical practice. We assess age at diagnosis and the role of family history in risk of breast cancer. Prospective follow-up of nurses' health study participants from 1980 to 2006.

Physical activity, sedentary behavior, and leukocyte telomere length in women.

Leukocyte telomere length (LTL) is a potential indicator of cellular aging; however, its relation to physical activity and sedentary behavior is unclear. The authors examined cross-sectionally associations among activity, sedentary behavior, and LTL among 7,813 women aged 43-70 years in the Nurses' Health Study. Participants self-reported activity by questionnaire in 1988 and 1992 and sedentary behavior in 1992.

Carotenoid intakes and risk of breast cancer defined by estrogen receptor and progesterone receptor status: a pooled analysis of 18 prospective cohort studies.

Background: Epidemiologic studies examining associations between carotenoid intakes and risk of breast cancer by estrogen receptor (ER) and progesterone receptor (PR) status are limited.

Objective: We investigated these associations in a pooled analysis of 18 cohort studies.

Design: Of 1,028,438 participants followed for a maximum follow-up of 26 y across studies, 33,380 incident invasive breast cancers were identified.

Meta-analyses identify 13 loci associated with age at menopause and highlight DNA repair and immune pathways.

To newly identify loci for age at natural menopause, we carried out a meta-analysis of 22 genome-wide association studies (GWAS) in 38,968 women of European descent, with replication in up to 14,435 women. In addition to four known loci, we identified 13 loci newly associated with age at natural menopause (at P < 5 × 10(-8)). Candidate genes located at these newly associated loci include genes implicated in DNA repair (EXO1, HELQ, UIMC1, FAM175A, FANCI, TLK1, POLG and PRIM1) and immune function (IL11, NLRP11 and PRRC2A (also known as BAT2)).

A dietary pattern derived to correlate with estrogens and risk of postmenopausal breast cancer.

Circulating estrogens are an established risk factor for breast cancer and some data suggest that diet may influence estrogen levels. Therefore, using a subsample (n = 550) of women from a large cohort, we applied reduced rank regression to identify a dietary pattern that was correlated with estradiol and estrone sulfate. We then adapted the pattern to be used with the full cohort (n = 67,802) and prospectively assessed its association with postmenopausal breast cancer.

Urinary estrogens and estrogen metabolites and subsequent risk of breast cancer among premenopausal women.

Endogenous estrogens and estrogen metabolism are hypothesized to be associated with premenopausal breast cancer risk but evidence is limited. We examined 15 urinary estrogens/estrogen metabolites and breast cancer risk among premenopausal women in a case-control study nested within the Nurses' Health Study II (NHSII). From 1996 to 1999, urine was collected from 18,521 women during the mid-luteal menstrual phase.

A prospective cohort study of coffee consumption and risk of endometrial cancer over a 26-year follow-up.

Background: Coffee has been reported to lower levels of estrogen and insulin, two hormones implicated in endometrial carcinogenesis, but prospective data on the relation between coffee consumption and risk of endometrial cancer are limited.

Methods: We prospectively assessed coffee consumption in relation to endometrial cancer risk in the Nurses' Health Study (NHS) with 67,470 female participants aged 34 to 59 in 1980. Cumulative average coffee intake was calculated with all available questionnaires to assess long-term effects.

Moderate alcohol consumption during adult life, drinking patterns, and breast cancer risk.

Context: Multiple studies have linked alcohol consumption to breast cancer risk, but the risk of lower levels of consumption has not been well quantified. In addition, the role of drinking patterns (ie, frequency of drinking and "binge" drinking) and consumption at different times of adult life are not well understood.

Objective: To evaluate the association of breast cancer with alcohol consumption during adult life, including quantity, frequency, and age at consumption.

High levels of nuclear heat-shock factor 1 (HSF1) are associated with poor prognosis in breast cancer.

Heat-shock factor 1 (HSF1) is the master transcriptional regulator of the cellular response to heat and a wide variety of other stressors. We previously reported that HSF1 promotes the survival and proliferation of malignant cells. At this time, however, the clinical and prognostic significance of HSF1 in cancer is unknown.