Family history of colorectal cancer is not associated with colorectal cancer survival regardless of microsatellite instability status.

Background: Individuals with a family history of colorectal cancer in first-degree relatives have an elevated risk of developing colorectal cancer themselves, particularly colorectal cancer exhibiting high microsatellite instability (MSI-high). Given that MSI-high colorectal cancer is associated with a favorable prognosis, it is plausible that having a family history of colorectal cancer could, in turn, be favorably associated with colorectal cancer survival.

Methods: This study comprised N = 4,284 incident colorectal cancer cases enrolled in the Colon Cancer Family Registry via population-based cancer registries.

Variation in the association between colorectal cancer susceptibility loci and colorectal polyps by polyp type.

We conducted a case-control study of the association between subsets of colorectal polyps, including adenomas and serrated polyps, and single-nucleotide polymorphisms (SNPs) related to colorectal cancer through prior genome-wide association studies (GWAS). Participants were enrollees in the Group Health Cooperative (Seattle, Washington) aged 24-79 years who received a colonoscopy from 1998 to 2007, donated a buccal or blood sample, and completed a structured questionnaire. We performed genotyping of 13 colorectal cancer susceptibility SNPs.

Reproductive windows, genetic loci, and breast cancer risk.

Purpose: The reproductive windows between age at menarche and age at first birth (standardized age at first birth) and from menarche to menopause (reproductive lifespan) may interact with genetic variants in association with breast cancer risk.

Methods: We assessed this hypothesis in 6131 breast cancer cases and 7274 controls who participated in the population-based Collaborative Breast Cancer Study. Risk factor information was collected through telephone interviews, and DNA samples were collected on a subsample (N= 1484 cases, 1307 controls) to genotype for 13 genome-wide association study-identified loci.

Identification of susceptibility loci for colorectal cancer in a genome-wide meta-analysis.

To identify common variants influencing colorectal cancer (CRC) risk, we performed a meta-analysis of five genome-wide association studies, comprising 5626 cases and 7817 controls of European descent. We conducted replication of top ranked single nucleotide polymorphisms (SNPs) in additional series totalling 14 037 cases and 15 937 controls, identifying a new CRC risk locus at 10q24.2 [rs1035209; odds ratio (OR) = 1.

Genetic variation in UGT genes modify the associations of NSAIDs with risk of colorectal cancer: colon cancer family registry.

The use of non-steroidal anti-inflammatory drugs (NSAIDs) is associated with reduced risk of colorectal neoplasia. Previous studies have reported that polymorphisms in NSAID-metabolizing enzymes central to NSAID metabolism including UDP-glucuronosyltransferases (UGT) and cytochrome P450 (CYP) 2C9 may modify this protective effect. We investigated whether 35 functionally relevant polymorphisms within CYP2C9 and UGT genes were associated with colorectal cancer risk or modified the protective effect of NSAIDs on colorectal cancer susceptibility, using 1,584 colorectal cancer cases and 2,516 unaffected sibling controls from the Colon Cancer Family Registry.

Fatal breast cancer risk in relation to use of unopposed estrogen and combined hormone therapy.

Use of combined hormone therapy (CHT) is associated with increased breast cancer incidence, but it is unclear whether this translates into increased breast cancer mortality. To address this question, we conducted a population-based nested case-control study in Saskatchewan, Canada, where a population-based prescription drug database has existed since 1975. We evaluated fatal breast cancer risk in relation to recency and duration of use of CHT and unopposed estrogen hormone therapy (EHT).

Modification of breast cancer risk according to age and menopausal status: a combined analysis of five population-based case-control studies.

While several risk factors for breast cancer have been identified, studies have not consistently shown whether these factors operate more strongly at certain ages or for just pre- or postmenopausal women. We evaluated whether risk factors for breast cancer differ according to age or menopausal status. Data from five population-based case-control studies conducted during 1988-2008 were combined and analyzed.

Dietary cadmium exposure and risk of breast, endometrial, and ovarian cancer in the Women's Health Initiative.

Background: In vitro and animal data suggest that cadmium, a heavy metal that contaminates some foods and tobacco plants, is an estrogenic endocrine disruptor. Elevated estrogen exposure is associated with breast, endometrial, and ovarian cancer risk.

Objectives: We examined the association between dietary cadmium intake and risk of these cancers in the large, well-characterized Women's Health Initiative (WHI).

Does risk of endometrial cancer for women without a germline mutation in a DNA mismatch repair gene depend on family history of endometrial cancer or colorectal cancer?

Objective: To determine whether risk of endometrial cancer for women without a germline mutation in a DNA mismatch repair (MMR) gene depends on family history of endometrial or colorectal cancer.

Methods: We retrospectively followed a cohort of 79,166 women who were recruited to the Colon Cancer Family Registry, after exclusion of women who were relatives of a carrier of a MMR gene mutation. The Kaplan-Meier failure method was used to estimate the cumulative risk of endometrial cancer.

Role of tumour molecular and pathology features to estimate colorectal cancer risk for first-degree relatives.

Objective: To estimate risk of colorectal cancer (CRC) for first-degree relatives of CRC cases based on CRC molecular subtypes and tumour pathology features.

Design: We studied a cohort of 33,496 first-degree relatives of 4853 incident invasive CRC cases (probands) who were recruited to the Colon Cancer Family Registry through population cancer registries in the USA, Canada and Australia. We categorised the first-degree relatives into four groups: 28,156 of 4095 mismatch repair (MMR)-proficient probands, 2302 of 301 MMR-deficient non-Lynch syndrome probands, 1799 of 271 suspected Lynch syndrome probands and 1239 of 186 Lynch syndrome probands.

A randomized trial to increase colonoscopy screening in members of high-risk families in the colorectal cancer family registry and cancer genetics network.

Background: Individuals with a strong family history of colorectal cancer have significant risk for colorectal cancer, although adherence to colonoscopy screening in these groups remains low. This study assessed whether a tailored telephone counseling intervention can increase adherence to colonoscopy in members of high-risk families in a randomized, controlled trial.

Methods: Eligible participants were recruited from two national cancer registries if they had a first-degree relative with colorectal cancer under age 60 or multiple affected family members, which included families that met the Amsterdam criteria for hereditary non-polyposis colon cancer (HNPCC), and if they were due for colonoscopy within 24 months.

Risk of colorectal cancer for carriers of mutations in MUTYH, with and without a family history of cancer.

We studied 2332 individuals with monoallelic mutations in MUTYH among 9504 relatives of 264 colorectal cancer (CRC) cases with a MUTYH mutation. We estimated CRC risks through 70 years of age of 7.2% for male carriers of monoallelic mutations (95% confidence interval [CI], 4.

Lifestyle factors and the risk of a second breast cancer after ductal carcinoma in situ.

Background: Little information exists on lifestyle factors that affect prognosis after treatment for ductal carcinoma in situ (DCIS) breast cancer. Improved understanding of the role of lifestyle factors is important to survivors wishing to reduce their risk of a second breast cancer diagnosis.

Methods: We examined the association between body mass index (BMI), physical activity, and alcohol intake, and risk of a second breast cancer diagnosis among 1,925 DCIS survivors in the Wisconsin In Situ Cohort.

Breast cancer susceptibility loci in association with age at menarche, age at natural menopause and the reproductive lifespan.

Background: Genome-wide association studies have identified single nucleotide polymorphisms (SNPs) associated with breast cancer risk. Some of these loci have unknown functional significance and may mediate the effects of hormonal exposures on breast cancer risk. We examined relationships between breast cancer susceptibility variants and menstrual/reproductive factors using data from two population-based studies.

Pre-diagnosis oophorectomy, estrogen therapy and mortality in a cohort of women diagnosed with breast cancer.

Introduction: Pre-diagnosis oophorectomy and estrogen therapy could impact mortality due to breast cancer and cardiovascular disease (CVD) among breast cancer survivors. Elective bilateral oophorectomy at the time of hysterectomy for benign conditions is not uncommon among US women.

Methods: We examined the association between pre-diagnosis total abdominal hysterectomy with bilateral salpingooophorectomy (TAHBSO) and both overall and cause-specific mortality in the Collaborative Breast Cancer Studies cohort.

Genetic variation in the inflammation and innate immunity pathways and colorectal cancer risk.

Background: It is widely accepted that chronic inflammation plays a role in the etiology of colorectal cancer. Using a two-stage design, we examined the associations between colorectal cancer and common variation in 37 key genes in the inflammation and innate immunity pathways.

Methods: In the discovery stage, 2,322 discordant sibships (2,535 cases, 3,915 sibling controls) from the Colorectal Cancer Family Registry were genotyped for more than 600 tagSNPs and 99 single-nucleotide polymorphisms (SNP) were selected for further examination based on strength of association.

Cadmium blood and urine concentrations as measures of exposure: NHANES 1999-2010.

Exposure to cadmium, a heavy metal present in cigarettes, can be assessed in both urine and blood. Few studies have compared the properties of concurrent measurements of urine cadmium (uCd) and blood cadmium (bCd) in relation to the duration and timing of a known exposure. In this study, bCd and uCd were modeled with data from the National Health and Nutrition Examination Survey (1999-2010).

Genetic predictors of circulating 25-hydroxyvitamin d and risk of colorectal cancer.

Background: Experimental evidence has demonstrated an antineoplastic role for vitamin D in the colon, and higher circulating 25-hydroxyvitamin D [25(OH)D] levels are consistently associated with a lower risk of colorectal cancer. Genome-wide association studies have identified loci associated with levels of circulating 25(OH)D. The identified single-nucleotide polymorphisms (SNPs) from four gene regions collectively explain approximately 5% of the variance in circulating 25(OH)D.

Disease-free survival by treatment after a DCIS diagnosis in a population-based cohort study.

Randomized trials have demonstrated the efficacy of radiation and tamoxifen in reducing risk of second events after breast-conserving surgery (BCS) for ductal carcinoma in situ (DCIS), but the comparative effectiveness of mastectomy, BCS, and adjuvant treatments have not been established in community practice. We examined disease-free survival (DFS) among 1,676 DCIS cases diagnosed during 1995-2006 in the population-based Wisconsin In Situ Cohort study. Information on patient and tumor characteristics, treatments, and second breast cancer events were collected via a comprehensive review of data from patient interviews, the statewide cancer registry, and pathology reports.

Pleiotropic effects of genetic risk variants for other cancers on colorectal cancer risk: PAGE, GECCO and CCFR consortia.

Objective: Genome-wide association studies have identified a large number of single nucleotide polymorphisms (SNPs) associated with a wide array of cancer sites. Several of these variants demonstrate associations with multiple cancers, suggesting pleiotropic effects and shared biological mechanisms across some cancers. We hypothesised that SNPs previously associated with other cancers may additionally be associated with colorectal cancer.

Contribution of HIV infection to mortality among cancer patients in Uganda.

Objective: HIV infection is associated with cancer risk. This relationship has resulted in a growing cancer burden, especially in resource-limited countries where HIV is highly prevalent. Little is known, however, about how HIV affects cancer survival in these settings.

Deciphering the genetic architecture of low-penetrance susceptibility to colorectal cancer.

Recent genome-wide association studies (GWASs) have identified common variants at 16 autosomal regions influencing the risk of developing colorectal cancer (CRC). To decipher the genetic basis of the association signals at these loci, we performed a meta-analysis of data from five GWASs, totalling 5626 cases and 7817 controls, using imputation to recover un-typed genotypes. To enhance our ability to discover low-frequency risk variants, in addition to using 1000 Genomes Project data as a reference panel, we made use of high-coverage sequencing data on 253 individuals, 199 with early-onset familial CRC.

The associations between a polygenic score, reproductive and menstrual risk factors and breast cancer risk.

We evaluated whether 13 single nucleotide polymorphisms (SNPs) identified in genome-wide association studies interact with one another and with reproductive and menstrual risk factors in association with breast cancer risk. DNA samples and information on parity, breastfeeding, age at menarche, age at first birth, and age at menopause were collected through structured interviews from 1,484 breast cancer cases and 1,307 controls who participated in a population-based case-control study conducted in three US states. A polygenic score was created as the sum of risk allele copies multiplied by the corresponding log odds estimate.