A pooled analysis of smoking and colorectal cancer: timing of exposure and interactions with environmental factors.

Background: Considerable evidence suggests that cigarette smoking is associated with a higher risk of colorectal cancer (CRC). What is unclear, however, is the impact of quitting smoking on risk attenuation and whether other risk factors for CRC modify this association.

Methods: We conducted a pooled analysis of eight studies, including 6,796 CRC cases and 7,770 controls, to evaluate the association between cigarette smoking history and CRC risk and to investigate potential effect modification by other risk factors.

The association between NSAID use and colorectal cancer mortality: results from the women's health initiative.

Background: Randomized trial evidence shows that nonsteroidal anti-inflammatory drug (NSAID) use, particularly long-term use, reduces the incidence of colorectal neoplasia. Recent data also suggests an inverse association between NSAID use and death due to colorectal cancer (CRC).

Methods: We examined the association between NSAID use and CRC mortality among 160,143 postmenopausal women enrolled in the Women's Health Initiative.

BRAF mutation status and survival after colorectal cancer diagnosis according to patient and tumor characteristics.

Background: BRAF mutations in colorectal cancer (CRC) are disproportionately observed in tumors exhibiting microsatellite instability (MSI) and are associated with other prognostic factors. The independent association between BRAF mutation status and CRC survival, however, remains unclear.

Methods: We evaluated the association between the BRAF c.

Temporal trends in incidence and mortality rates for colorectal cancer by tumor location: 1975-2007.

Objectives: We evaluated changes in colorectal cancer (CRC) incidence and mortality by anatomic site to assess the possible impact of CRC screening.

Methods: Using data from 9 Surveillance, Epidemiology, and End Results cancer registries, we estimated trends in 1975-2007 CRC incidence and 1985-2007 incidence-based mortality. We evaluated trends separately for proximal and distal CRC, overall and by stage, tumor site, and race.

Migraine history, nonsteroidal anti-inflammatory drug use, and risk of postmenopausal endometrial cancer.

Endometrial cancer is primarily a hormonally mediated disease. As such, factors that mediate or reflect exposure to estrogens, or that mediate response to such exposure, may plausibly be associated with endometrial cancer risk. History of migraines, another hormonally mediated condition, has recently been associated with a reduced risk of hormone receptor-positive breast cancer; however, the relationship between migraines and endometrial cancer has not previously been explored.

Colorectal endoscopy, advanced adenomas, and sessile serrated polyps: implications for proximal colon cancer.

Objectives: Colonoscopy is associated with a decreased risk of colorectal cancer but may be more effective in reducing the risk of distal than proximal malignancies. To gain insight into the differences between proximal and distal colon endoscopic performance, we conducted a case-control study of advanced adenomas, the primary targets of colorectal endoscopy screening, and sessile serrated polyps (SSPs), newly recognized precursor lesions for a colorectal cancer subset that occurs most often in the proximal colon.

Methods: The Group Health-based study population included 213 advanced adenoma cases, 172 SSP cases, and 1,704 controls aged 50-79 years, who received an index colonoscopy from 1998-2007.

Association between colorectal cancer susceptibility loci and survival time after diagnosis with colorectal cancer.

Genome-wide association studies have identified 16 germline single-nucleotide polymorphisms (SNPs) that are associated with colorectal cancer (CRC) incidence. We examined the relationship between these SNPs and survival of 2611 individuals with CRC, enrolled in 5 cohort studies. We used Cox regression analysis to associate SNPs with overall and CRC-specific survival times.

Breast density, body mass index, and risk of tumor marker-defined subtypes of breast cancer.

Purpose: Breast density and body mass index (BMI) are correlated attributes and are both potentially modifiable risk factors for breast cancer. However, relationships between these factors and risk of molecularly-defined subtypes of breast cancer have not been established.

Methods: We used breast density and BMI data collected by the Breast Cancer Surveillance Consortium from 1,054,466 women ages 40 to 84 years receiving mammography, including 13,797 women subsequently diagnosed with breast cancer.

Impact of colon cancer screening on family history phenotype.

Background: If effective cancer screening is more common in people with a family history of cancer, the relationship between family history and cancer incidence may become distorted.

Methods: To assess the impact of screening on the association between colorectal cancer family history and risk of colorectal cancer, we developed a model to simulate screening patterns in those with and without a family history.

Results: The introduction of screening reduces the apparent risk of colorectal cancer associated with family history in subsequent generations.

Early-life factors and breast cancer risk in Hispanic women: the role of adolescent body size.

Background: Adult body size has long been known to influence breast cancer risk, and there is now increasing evidence that childhood and adolescent body size may also play a role.

Methods: We assessed the association with body size at ages 10, 15, and 20 years in 475 premenopausal and 775 postmenopausal Hispanic women who participated in a population-based case-control study of breast cancer conducted from 1995 to 2004 in the San Francisco Bay Area. We used unconditional logistic regression to estimate ORs and 95% CIs for the associations with self-reported relative weight compared with peers and body build at ages 10, 15, and 20 years.

Case studies addressing human pharmacokinetic uncertainty using a combination of pharmacokinetic simulation and alternative first in human paradigms.

PF-184298 ((S)-2,3-dichloro-N-isobutyl-N-pyrrolidin-3-ylbenzamide) and PF-4776548 ((3-(4-fluoro-2-methoxy-benzyl)-7-hydroxy-8,9-dihydro-3H,7H-pyrrolo[2,3-c][1,7]naphthyridin-6-one)) are novel compounds which were selected to progress to human studies. Discordant human pharmacokinetic predictions arose from pre-clinical in vivo studies in rat and dog, and from human in vitro studies, resulting in a clearance prediction range of 3 to >20 mL min⁻¹ kg⁻¹ for PF-184298, and 5 to >20 mL min⁻¹ kg⁻¹ for PF-4776548. A package of work to investigate the discordance for PF-184298 is described.

Long-term use of continuous-combined estrogen-progestin hormone therapy and risk of endometrial cancer.

The daily administered dose of progestin in continuous-combined estrogen-progestin therapy is provided to counteract the proliferative effect of estrogen on the postmenopausal endometrium. However, there remains some uncertainty as to whether use of such a combined regimen, over the long term, is associated with an altered risk of endometrial cancer. We pooled data from four population-based case-control studies of endometrial cancer in western Washington State.

Pregabalin assay in a patient with widespread neuropathic pain and late onset gluten intolerance.

Objective:  The aim of this study was to determine the pharmacokinetics of pregabalin in a patient with malabsorption secondary to celiac disease and compare the findings with the data available from pre-existing studies in healthy volunteer controls.

Methods: A 39-year-old man consented to a 24-hour pregabalin assay with sequential pre and post-dose blood sampling.

Results: The blood levels measured in this subject were no different to healthy male volunteers enrolled in previous studies.

Examination of Bacillus anthracis spores by multiparameter flow cytometry.

The ability to rapidly differentiate Bacillus anthracis spores from spores belonging to other Bacillus spp. is potentially useful for combating the intentional release of this biothreat agent. Furthermore, not all B.

Results from a low-energy analysis of the CDMS II germanium data.

We report results from a reanalysis of data from the Cryogenic Dark Matter Search (CDMS II) experiment at the Soudan Underground Laboratory. Data taken between October 2006 and September 2008 using eight germanium detectors are reanalyzed with a lowered, 2 keV recoil-energy threshold, to give increased sensitivity to interactions from weakly interacting massive particles (WIMPs) with masses below ∼10  GeV/c(2). This analysis provides stronger constraints than previous CDMS II results for WIMP masses below 9  GeV/c(2) and excludes parameter space associated with possible low-mass WIMP signals from the DAMA/LIBRA and CoGeNT experiments.

Prediagnostic smoking history, alcohol consumption, and colorectal cancer survival: the Seattle Colon Cancer Family Registry.

Background: Smoking and alcohol consumption are associated with an increased risk of developing colorectal cancer. However, it is unclear whether these exposures are associated with survival after colorectal cancer diagnosis.

Methods: Men and women diagnosed with incident colorectal cancer between 1998 and 2007 in 13 counties in western Washington State were identified by using the Surveillance, Epidemiology, and End Results cancer registry.

Body size, physical activity, and risk of triple-negative and estrogen receptor-positive breast cancer.

Background: Triple-negative breast cancer, characterized by a lack of hormone receptor and HER2 expression, is associated with a particularly poor prognosis. Focusing on potentially modifiable breast cancer risk factors, we examined the relationship between body size, physical activity, and triple-negative disease risk.

Methods: Using data from 155,723 women enrolled in the Women's Health Initiative (median follow-up, 7.

Smoking and alcohol consumption in relation to risk of triple-negative breast cancer in a cohort of postmenopausal women.

Purpose: Little is known about the risk factors for triple-negative breast cancer (TNBC), which has a worse prognosis compared to hormone receptor-positive breast cancer. We examined the association of smoking and alcohol intake with TNBC and estrogen receptor-positive (ER+) breast cancer.

Methods: Among 148,030 women enrolled in the Women's Health Initiative, 300 TNBC cases and 2,479 ER+ cases were identified over a median of 8.

Reproductive history and oral contraceptive use in relation to risk of triple-negative breast cancer.

Background: Triple-negative (ie, estrogen receptor [ER], progesterone receptor, and HER2 negative) breast cancer occurs disproportionately among African American women compared with white women and is associated with a worse prognosis than ER-positive (ER+) breast cancer. Hormonally mediated risk factors may be differentially related to risk of triple-negative and ER+ breast cancers.

Methods: Using data from 155,723 women enrolled in the Women's Health Initiative, we assessed associations between reproductive and menstrual history, breastfeeding, oral contraceptive use, and subtype-specific breast cancer risk.

Reproductive history and risk of three breast cancer subtypes defined by three biomarkers.

Breast cancer subtypes defined by estrogen receptor (ER), progesterone receptor (PR), and HER2 expression are biologically distinct and thus, may have distinct etiologies. In particular, it is plausible that risk factors operating through hormonal mechanisms are differentially related to risk of such tumor subtypes. Using data from the Breast Cancer Surveillance Consortium, we explored associations between reproductive history and three breast cancer subtypes.

Adult body size, hormone receptor status, and premenopausal breast cancer risk in a multiethnic population: the San Francisco Bay Area breast cancer study.

Large body size has been associated with a reduced risk of premenopausal breast cancer in non-Hispanic white women. Data on other racial/ethnic populations are limited. The authors examined the association between premenopausal breast cancer risk and adult body size in 672 cases and 808 controls aged ≥35 years from a population-based case-control study conducted in 1995-2004 in the San Francisco Bay Area (Hispanics: 375 cases, 483 controls; African Americans: 154 cases, 160 controls; non-Hispanic whites: 143 cases, 165 controls).

Increased cancer risks for relatives of very early-onset breast cancer cases with and without BRCA1 and BRCA2 mutations.

Background: Little is known regarding cancer risks for relatives of women with very early-onset breast cancer.

Methods: We studied 2208 parents and siblings of 504 unselected population-based Caucasian women with breast cancer diagnosed before age 35 years (103 from USA, 124 from Canada and 277 from Australia), 41 known to carry a mutation (24 in BRCA1, 16 in BRCA2 and one in both genes). Cancer-specific standardised incidence ratios (SIRs) were estimated by comparing the number of affected relatives (50% verified overall) with that expected based on incidences specific for country, sex, age and year of birth.

Family history of breast cancer in first-degree relatives and triple-negative breast cancer risk.

Triple-negative breast cancer accounts for less than 20% of breast cancers overall, but is the predominant subtype among carriers of mutations in BRCA1. However, few studies have assessed the association between breast cancer family history and risk of triple-negative breast cancer. We examined the relationship between having a family history of breast cancer in first-degree relatives and risk of triple-negative breast cancer, and risk of two other breast cancer subtypes defined by tumor marker expression.