Genetic variability in IL23R and risk of colorectal adenoma and colorectal cancer.

Inflammatory processes, including, specifically, the inflammatory conditions Crohn's disease (CD) and ulcerative colitis (UC) predispose to colorectal cancer. Interleukin-23 is involved in pro-inflammatory signaling; genetic variation in the interleukin-23 receptor (IL23R) has been consistently associated with CD and UC risk. In three case-control studies of colorectal adenoma (n=485 cases/578 controls), colon cancer (n=1424 cases/1780 controls) and rectal cancer (n=583 cases/775 controls), we investigated associations with 18 candidate and tagSNPs in IL23R.

Diet and colorectal cancer: analysis of a candidate pathway using SNPS, haplotypes, and multi-gene assessment.

There is considerable biologic plausibility to the hypothesis that genetic variability in pathways involved in insulin signaling and energy homeostasis may modulate dietary risk associated with colorectal cancer. We utilized data from 2 population-based case-control studies of colon (n = 1,574 cases, 1,970 controls) and rectal (n = 791 cases, 999 controls) cancer to evaluate genetic variation in candidate SNPs identified from 9 genes in a candidate pathway: PDK1, RP6KA1, RPS6KA2, RPS6KB1, RPS6KB2, PTEN, FRAP1 (mTOR), TSC1, TSC2, Akt1, PIK3CA, and PRKAG2 with dietary intake of total energy, carbohydrates, fat, and fiber. We employed SNP, haplotype, and multiple-gene analysis to evaluate associations.

Antioxidant supplement use after breast cancer diagnosis and mortality in the Life After Cancer Epidemiology (LACE) cohort.

Background: There is concern that antioxidant supplement use during chemotherapy and radiation therapy may decrease treatment effects, yet the effects of such supplements on recurrence and survival are largely unknown.

Methods: The authors prospectively examined the associations between antioxidant use after breast cancer (BC) diagnosis and BC outcomes in 2264 women in the Life After Cancer Epidemiology (LACE) cohort. The cohort included women who were diagnosed with early stage, primary BC from 1997 to 2000 who enrolled, on average, 2 years postdiagnosis.

Meeting the physical activity guidelines and survival after breast cancer: findings from the after breast cancer pooling project.

The 2008 Physical Activity (PA) Guidelines recommend engaging in at least 2.5 h (10 MET-hours/week) of moderate intensity PA per week (defined as 4 METs) to reduce risk of morbidity and mortality. This analysis was conducted to investigate whether this recommendation can be extended to breast cancer survivors.

The effect of calcium plus vitamin D on risk for invasive cancer: results of the Women's Health Initiative (WHI) calcium plus vitamin D randomized clinical trial.

In the Women's Health Initiative (WHI) trial of calcium plus vitamin D (CaD), we examined the treatment effect on incidence and mortality for all invasive cancers. Postmenopausal women (N = 36,282) were randomized to 1,000 mg of elemental calcium with 400 IU vitamin D3 or placebo. Cox models estimated risk of cancer incidence and mortality.

Evaluation and comparison of food records, recalls, and frequencies for energy and protein assessment by using recovery biomarkers.

The food frequency questionnaire approach to dietary assessment is ubiquitous in nutritional epidemiology research. Food records and recalls provide approaches that may also be adaptable for use in large epidemiologic cohorts, if warranted by better measurement properties. The authors collected (2007-2009) a 4-day food record, three 24-hour dietary recalls, and a food frequency questionnaire from 450 postmenopausal women in the Women's Health Initiative prospective cohort study (enrollment, 1994-1998), along with biomarkers of energy and protein consumption.

Meta-analysis of new genome-wide association studies of colorectal cancer risk.

Colorectal cancer is the second leading cause of cancer death in developed countries. Genome-wide association studies (GWAS) have successfully identified novel susceptibility loci for colorectal cancer. To follow up on these findings, and try to identify novel colorectal cancer susceptibility loci, we present results for GWAS of colorectal cancer (2,906 cases, 3,416 controls) that have not previously published main associations.

The After Breast Cancer Pooling Project: rationale, methodology, and breast cancer survivor characteristics.

The After Breast Cancer Pooling Project was established to examine the role of physical activity, adiposity, dietary factors, supplement use, and quality of life (QOL) in breast cancer prognosis. This paper presents pooled and harmonized data on post-diagnosis lifestyle factors, clinical prognostic factors, and breast cancer outcomes from four prospective cohorts of breast cancer survivors (three US-based and one from Shanghai, China) for 18,314 invasive breast cancer cases diagnosed between 1976 and 2006. Most participants were diagnosed with stage I-II breast cancer (84.

Multivitamin use and breast cancer outcomes in women with early-stage breast cancer: the Life After Cancer Epidemiology study.

Little is known about the relation of multivitamin use to breast cancer outcomes. 2,236 women diagnosed from 1997 to 2000 with early-stage breast cancer (Stage I ≥ 1 cm, II, or IIIA) were enrolled about 2 years post-diagnosis, primarily from the Kaiser Permanente Northern California Cancer Registry (83%). Multivitamin use pre-diagnosis and post-diagnosis was assessed via mailed questionnaire.

Candidate pathway polymorphisms in one-carbon metabolism and risk of rectal tumor mutations.

We examined candidate polymorphisms in genes involved in the folate-mediated, one-carbon metabolism pathway, DNMT1 1311V, MTHFD1 R134K and R653Q, MTHFR R594Q, MTR D919G, MTRR H595Y and I22M, SHMT1 L474F, SLC19A1 H27R, and TDG G199S, and associations with rectal tumor characteristics. We hypothesized that these candidate genes would influence CpG Island Methylator Phenotype and potentially KRAS2 or TP53 tumors. Data from a population-based study of 747 rectal cases (593 with tumor markers) and 956 controls were evaluated using generalized estimating equations.

Examining the influence of beta blockers and ACE inhibitors on the risk for breast cancer recurrence: results from the LACE cohort.

There is increasing interest in the relationship between host lifestyle factors and the outcomes of cancer treatment. Behavioral factors, comorbid conditions, and non-cancer-related pharmaceutical exposures may affect breast cancer (BC) outcomes. We used observational data from the LACE Study cohort (women with early stage BC from the Kaiser Permanente Northern California Cancer Registry) to examine the association between beta blockers (BBs) and/or angiotensin-converting enzyme inhibitors (ACEi) and BC recurrence, BC-specific mortality, and overall mortality.

Variation in the CYP19A1 gene and risk of colon and rectal cancer.

CYP19A1, or aromatase, influences estrogen-metabolizing enzymes and may influence cancer risk. We examine variation in the CYP19A1 gene and risk of colorectal cancer using data from population-based case-control studies (colon n = 1,574 cases, 1,970 controls; rectal n = 791 cases, 999 controls). Four SNPs were statistically significantly associated with colon cancer and four were associated with rectal cancer.

Nutrients in folate-mediated, one-carbon metabolism and the risk of rectal tumors in men and women.

In an investigation of rectal tumors characterized by CpG island methylator phenotype (CIMP), KRAS2 mutation, and TP53 mutation, we examined associations with dietary and supplemental folate, riboflavin, vitamins B(6) and B(12), and methionine, nutrients involved in folate-mediated 1-carbon metabolism. We also examined folate intake and common MTHFR polymorphisms in relation to CIMP. Data from a population-based study of 951 cases (750 with tumor markers) and 1,205 controls were evaluated using multiple logistic regression models and generalized estimating equations.

Genetic variation in bone morphogenetic protein and colon and rectal cancer.

Bone morphogenetic proteins (BMP) are part of the TGF-β-signaling pathway; genetic variation in these genes may be involved in colorectal cancer. In this study, we evaluated the association between genetic variation in BMP1 (11 tagSNPs), BMP2 (5 tagSNPs), BMP4 (3 tagSNPs), BMPR1A (9 tagSNPs), BMPR1B (21 tagSNPs), BMPR2 (11 tagSNPs) and GDF10 (7 tagSNPs) with risk of colon and rectal cancer and tumor molecular phenotype. We used data from population-based case-control studies (colon cancer n = 1,574 cases, 1,970 controls; rectal cancer n = 791 cases, 999 controls).

Genetic variation in the transforming growth factor-β signaling pathway and survival after diagnosis with colon and rectal cancer.

Background: The transforming growth factor-β (TGF-β) signaling pathway is involved in many aspects of tumorigenesis, including angiogenesis and metastasis. The authors evaluated this pathway in association with survival after a diagnosis of colon or rectal cancer.

Methods: The study included 1553 patients with colon cancer and 754 patients with rectal cancer who had incident first primary disease and were followed for a minimum of 7 years after diagnosis.

Soy food consumption and breast cancer prognosis.

Background: Contrary to earlier clinical studies suggesting that soy may promote breast tumor growth, two recent studies show that soy-containing foods are not adversely related to breast cancer prognosis. We examined, using data from the Women's Healthy Eating and Living (WHEL) study, the effect of soy intake on breast cancer prognosis.

Methods: Three thousand eighty-eight breast cancer survivors, diagnosed between 1991 and 2000 with early-stage breast cancer and participating in WHEL, were followed for a median of 7.

IGF1 and risk of additional breast cancer in the WHEL study.

IGF1, IGF-binding protein-3 (IGFBP-3), IGFBP-1, insulin, leptin, and adiponectin have been inconsistently associated with breast cancer incidence. We explore how these factors are related to breast cancer recurrence and how tamoxifen treatment is related to IGF1 levels among breast cancer survivors in the Women's Healthy Eating and Living (WHEL) study. A nested case-control design was used to match breast cancer cases (who had an additional breast cancer event) to controls.

Efficacy of escitalopram for hot flashes in healthy menopausal women: a randomized controlled trial.

Context: Concerns regarding the risks associated with estrogen and progesterone to manage menopausal symptoms have resulted in its declining use and increased interest in nonhormonal treatments with demonstrated efficacy for hot flashes.

Objective: To determine the efficacy and tolerability of 10 to 20 mg/d escitalopram, a selective serotonin reuptake inhibitor, in alleviating the frequency, severity, and bother of menopausal hot flashes.

Design, Setting, And Patients: A multicenter, 8-week, randomized, double-blind, placebo-controlled, parallel group trial that enrolled 205 women (95 African American; 102 white; 8 other) between July 2009 and June 2010.

Marine fatty acid intake is associated with breast cancer prognosis.

EPA and DHA, long-chain (n-3) PUFA largely obtained from fish, inhibit the proliferation of breast cancer cells in vitro and reduce the initiation and progression of breast tumors in laboratory animals. Our purpose in this analysis was to examine whether intake of these marine fatty acids (EPA and DHA) were associated with prognosis in a cohort of women who had been diagnosed and treated for early stage breast cancer (n = 3,081). Median follow-up was 7.

Characterization of the association between 8q24 and colon cancer: gene-environment exploration and meta-analysis.

Background: Genome-wide association studies and subsequent replication studies have shown that single nucleotide polymorphisms (SNPs) in the chromosomal region 8q24 are associated with colorectal cancer susceptibility.

Methods: We examined 11 SNP markers in the 8q24 region between 128.47 and 128.

Associations between genetic variation in RUNX1, RUNX2, RUNX3, MAPK1 and eIF4E and riskof colon and rectal cancer: additional support for a TGF-β-signaling pathway.

The Runt-related transcription factors (RUNX), mitogen-activated protein kinase (MAPK) 1 and eukaryotic translation initiation factor 4E (eIF4E) are potentially involved in tumorigenesis. We evaluated genetic variation in RUNX1 (40 tagSNPs), RUNX2 (19 tagSNPs), RUNX3 (9 tagSNPs), MAPK1 (6 tagSNPs), eIF4E (3 tagSNPs), eIF4EBP2 (2 tagSNP) and eIF4EBP3 (2 tagSNPs) to determine associations with colorectal cancer (CRC). We used data from population-based studies (colon cancer n = 1555 cases, 1956 controls; rectal cancer n = 754 cases, 959 controls with complete genotype data).

Characterization of 9p24 risk locus and colorectal adenoma and cancer: gene-environment interaction and meta-analysis.

Background: A potential susceptibility locus for colorectal cancer on chromosome 9p24 (rs719725) was initially identified through a genome-wide association study, though replication attempts have been inconclusive.

Methods: We genotyped this locus and explored interactions with known risk factors as potential sources of heterogeneity, which may explain the previously inconsistent replication. We included Caucasians with colorectal adenoma or colorectal cancer and controls from 4 studies (total 3,891 cases, 4,490 controls): the Women's Health Initiative (WHI); the Diet, Activity and Lifestyle Study (DALS); a Minnesota population-based case-control study (MinnCCS); and the Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial (PLCO).

Genetic variation in C-reactive protein in relation to colon and rectal cancer risk and survival.

C-reactive protein (CRP), a biomarker of inflammation, has been shown to be influenced by genetic variation in the CRP gene. In this study, we test the hypothesis that genetic variation in CRP influences both the risk of developing colon and rectal cancer and survival. Two population-based studies of colon cancer (n = 1,574 cases, 1,970 controls) and rectal (n = 791 cases, 999 controls) were conducted.

Long-term prognostic role of functional limitations among women with breast cancer.

Background: The long-term prognostic role of functional limitations among women with breast cancer is poorly understood.

Methods: We studied a cohort of 2202 women with breast cancer at two sites in the United States, who provided complete information on body functions involving endurance, strength, muscular range of motion, and small muscle dexterity following initial adjuvant treatment. Associations of baseline functional limitations with survival were evaluated in delayed entry Cox proportional hazards models, with adjustment for baseline sociodemographic factors, body mass index, smoking, physical activity, comorbidity, tumor characteristics, and treatment.

Alcohol consumption and breast cancer recurrence and survival among women with early-stage breast cancer: the life after cancer epidemiology study.

Purpose: To examine the association of alcohol consumption after breast cancer diagnosis with recurrence and mortality among early-stage breast cancer survivors.

Patients And Methods: Patients included 1,897 LACE study participants diagnosed with early-stage breast cancer between 1997 and 2000 and recruited on average 2 years postdiagnosis, primarily from the Kaiser Permanente Northern California Cancer Registry. Alcohol consumption (ie, wine, beer, and liquor) was assessed at cohort entry using a food frequency questionnaire.