Predictors of health-related quality of life in patients with colorectal cancer

<p>Abstract</p> <p>Background</p> <p>Most studies that have identified variables associated with the health-related quality of life (HRQL) of patients with colorectal cancer have been cross-sectional or included patients with other diagnoses. The objectives of this study were to identify predictors of HRQL in patients with colorectal cancer and interpret the clinical importance of the results.</p> <p>Methods</p> <p>We conducted a population-based longitudinal study of patients identified through three regions of the California Cancer Registry. Surveys were completed by 568 patients approximately 9 and 19 months post-diagnosis. Three HRQL outcomes from the Functional Assessment of Cancer Therapy – Colorectal (FACT-C) were evaluated: social/family well-being (SWB), emotional well-being (EWB) and the Trial Outcome Index (TOI), which is a colorectal cancer-specific summary measure of physical function and well-being. Sociodemographic, cancer/health, and healthcare variables were assessed in multivariable regression models. We computed the difference in predicted HRQL scores corresponding to a large difference in a predictor variable, defined as a 1 standard deviation difference for interval variables or the difference relative to the reference category for nominal variables. The effect of an explanatory variable on HRQL was considered clinically meaningful if the predicted score difference was at least as large as the minimally important difference.</p> <p>Results</p> <p>Common predictors of better TOI, SWB and EWB were better general health and factors related to better perceived quality of cancer care. Predictor variables in addition to general health and perceived quality of care were identified only for SWB. Being married/living as married was associated with better SWB, whereas being male or of Hispanic ethnicity was associated with worse SWB. Among the sociodemographic, cancer/health, and healthcare variables evaluated, only Hispanic ethnicity had a clinically meaningful effect on an HRQL outcome.</p> <p>Conclusion</p> <p>Our findings, particularly the information on the clinical importance of predictor variables, can help clinicians identify patients who may be at risk for poor future HRQL. Potentially modifiable factors were related to perceived quality of cancer care; thus, future research should evaluate whether improving these factors improves HRQL.</p

Breast cancer incidence and mortality trends in an affluent population: Marin County, California, USA, 1990–1999

BACKGROUND: Elevated rates of breast cancer in affluent Marin County, California, were first reported in the early 1990s. These rates have since been related to higher regional prevalence of known breast cancer risk factors, including low parity, education, and income. Close surveillance of Marin County breast cancer trends has nevertheless continued, in part because distinctive breast cancer patterns in well-defined populations may inform understanding of breast cancer etiology. METHODS: Using the most recent incidence and mortality data available from the California Cancer Registry, we examined rates and trends for 1990–1999 for invasive breast cancer among non-Hispanic, white women in Marin County, in other San Francisco Bay Area counties, and in other urban California counties. Rates were age adjusted to the 2000 US standard, and temporal changes were evaluated with weighted linear regression. RESULTS: Marin County breast cancer incidence rates between 1990 and 1999 increased 3.6% per year (95% confidence interval, 1.8–5.5), six times more rapidly than in comparison areas. The increase was limited to women aged 45–64 years, in whom rates increased at 6.7% per year (95% confidence interval, 3.8–9.6). Mortality rates did not change significantly in Marin County despite 3–5% yearly declines elsewhere. CONCLUSION: Patterns of breast cancer incidence and mortality in Marin County are unlike those in other California counties, and they are probably explained by Marin County's unique sociodemographic characteristics. Similar trends may have occurred in other affluent populations for which available data do not permit annual monitoring of cancer occurrence

Early dissemination of bevacizumab for advanced colorectal cancer: a prospective cohort study

<p>Abstract</p> <p>Background</p> <p>We describe early dissemination patterns for first-line bevacizumab given for metastatic colorectal cancer treatment.</p> <p>Methods</p> <p>We analyzed patient surveys and medical records for a population-based cohort with metastatic colorectal cancer treated in multiple regions and health systems in the United States (US). Eligible patients were diagnosed with metastatic colorectal cancer and initiated first-line chemotherapy after US Food & Drug Administration (FDA) bevacizumab approval in February 2004. First-line bevacizumab therapy was defined as receiving bevacizumab within 8 weeks of starting chemotherapy for metastatic colorectal cancer. We evaluated factors associated with first-line bevacizumab treatment using logistic regression.</p> <p>Results</p> <p>Among 355 patients, 31% received first-line bevacizumab in the two years after FDA approval, including 26% of men, 41% of women, and 16% of those ≥ 75 years. Use rose sharply within 6 months after FDA approval, then plateaued. 20% of patients received bevacizumab in combination with irinotecan; 53% received it with oxaliplatin. Men were less likely than women to receive bevacizumab (adjusted OR 0.55; 95% CI 0.32-0.93; p = 0.026). Patients ≥ 75 years were less likely to receive bevacizumab than patients < 55 years (adjusted OR 0.13; 95% CI 0.04-0.46; p = 0.001).</p> <p>Conclusions</p> <p>One-third of eligible metastatic colorectal cancer patients received first-line bevacizumab shortly after FDA approval. Most patients did not receive bevacizumab as part of the regimen used in the pivotal study leading to FDA approval.</p

Chemotherapy use and patient treatment preferences in advanced colorectal cancer: A prospective cohort study

Our objective was to determine how patient preferences guide the course of palliative chemotherapy for advanced colorectal cancer

A novel de novo BRCA1 mutation in a Chinese woman with early onset breast cancer

Germline mutations in the two breast cancer susceptibility genes, BRCA1 and BRCA2 account for a significant portion of hereditary breast/ovarian cancer. De novo mutations such as multiple exon deletion are rarely occurred in BRCA1 and BRCA2. During our mutation screening for BRCA1/2 genes to Chinese women with risk factors for hereditary breast/ovarian cancer, we identified a novel germline mutation, consisting of a deletion from exons 1 to 12 in BRCA1 gene, in a patient diagnosed with early onset triple negative breast cancer with no family history of cancer. None of her parents carried the mutation and molecular analysis showed that this novel de novo germline mutation resulted in down-regulation of BRCA1 gene expression

Fine-mapping of genome-wide association study-identified risk loci for colorectal cancer in African Americans

Genome-wide association studies of colorectal cancer (CRC) in Europeans and Asians have identified 21 risk susceptibility regions [29 index single-nucleotide polymorphisms (SNPs)]. Characterizing these risk regions in diverse racial groups with different linkage disequilibrium (LD) structure can help localize causal variants. We examined associations between CRC and all 29 index SNPs in 6597 African Americans (1894 cases and 4703 controls). Nine SNPs in eight regions (5q31.1, 6q26-q27, 8q23.3, 8q24.21, 11q13.4, 15q13.3, 18q21.1 and 20p12.3) formally replicated in our data with one-sided P-values <0.05 and the same risk directions as reported previously. We performed fine-mapping of the 21 risk regions (including 250 kb on both sides of the index SNPs) using genotyped and imputed markers at the density of the 1000 Genomes Project to search for additional or more predictive risk markers. Among the SNPs correlated with the index variants, two markers, rs12759486 (or rs7547751, a putative functional variant in perfect LD with it) in 1q41 and rs7252505 in 19q13.1, were more strongly and statistically significantly associated with CRC (P < 0.0006). The average per allele risk was improved using the replicated index variants and the two new markers (odds ratio = 1.14, P = 6.5 × 10−16) in African Americans, compared with using all index SNPs (odds ratio = 1.07, P = 3.4 × 10−10). The contribution of the two new risk SNPs to CRC heritability was estimated to be 1.5% in African Americans. This study highlights the importance of fine-mapping in diverse populations

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

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. The sites have developed core family history and epidemiology questionnaires, data dictionaries, and common protocols for biospecimen collection and processing and pathology review. An Informatics Center has been established to collate, manage, and distribute core data. As of September 2003, 9116 population-based and 2834 clinic-based families have been enrolled, including 2346 families from minority populations. Epidemiology questionnaire data are available for 6779 affected probands (with a personal history of breast cancer), 4116 unaffected probands, and 16,526 relatives with or without a personal history of breast or ovarian cancer. The biospecimen repository contains blood or mouthwash samples for 6316 affected probands, 2966 unaffected probands, and 10,763 relatives, and tumor tissue samples for 4293 individuals. This resource is available to internal and external researchers for collaborative, interdisciplinary, and translational studies of the genetic epidemiology of breast cancer. Detailed information can be found at the URL http://www.cfr.epi.uci.edu/

Wine and other alcohol consumption and risk of ovarian cancer in the California Teachers Study cohort

OBJECTIVE: Whether alcohol consumption influences ovarian cancer risk is unclear. Therefore, we investigated the association between alcohol intake at various ages and risk of ovarian cancer. METHODS: Among 90,371 eligible members of the California Teachers Study cohort who completed a baseline alcohol assessment in 1995–1996, 253 women were diagnosed with epithelial ovarian cancer by the end of 2003. Multivariate Cox proportional hazards regression analysis was performed to estimate relative risks (RRs) and 95% confidence intervals (CIs). RESULTS: Consumption of total alcohol, beer, or liquor in the year prior to baseline, at ages 30–35 years, or at ages 18–22 years was not associated with risk of ovarian cancer. Consumption of at least one glass per day of wine, compared to no wine, in the year before baseline was associated with increased risk of developing ovarian cancer: RR = 1.57 (95% CI 1.11–2.22), P(trend) = 0.01. The association with wine intake at baseline was particularly strong among peri-/post-menopausal women who used estrogen-only hormone therapy and women of high socioeconomic status. CONCLUSIONS: Alcohol intake does not appear to affect ovarian cancer risk. Constituents of wine other than alcohol or, more likely, unmeasured determinants of wine drinking were associated with increased risk of ovarian cancer

Trans-ethnic genome-wide association study of colorectal cancer identifies a new susceptibility locus in VTI1A

The genetic basis of sporadic colorectal cancer (CRC) is not well explained by known risk polymorphisms. Here we perform a meta-analysis of two genome-wide association studies in 2,627 cases and 3,797 controls of Japanese ancestry and 1,894 cases and 4,703 controls of African ancestry, to identify genetic variants that contribute to CRC susceptibility. We replicate genome-wide statistically significant associations (P < 5×10−8) in 16,823 cases and 18,211 controls of European ancestry. This study reveals a new pan-ethnic CRC risk locus at 10q25 (rs12241008, intronic to VTI1A; P=1.4×10−9), providing additional insight into the etiology of CRC and highlighting the value of association mapping in diverse populations

Assessing interactions between the associations of common genetic susceptibility variants, reproductive history and body mass index with breast cancer risk in the breast cancer association consortium: a combined case-control study.

INTRODUCTION: Several common breast cancer genetic susceptibility variants have recently been identified. We aimed to determine how these variants combine with a subset of other known risk factors to influence breast cancer risk in white women of European ancestry using case-control studies participating in the Breast Cancer Association Consortium. METHODS: We evaluated two-way interactions between each of age at menarche, ever having had a live birth, number of live births, age at first birth and body mass index (BMI) and each of 12 single nucleotide polymorphisms (SNPs) (10q26-rs2981582 (FGFR2), 8q24-rs13281615, 11p15-rs3817198 (LSP1), 5q11-rs889312 (MAP3K1), 16q12-rs3803662 (TOX3), 2q35-rs13387042, 5p12-rs10941679 (MRPS30), 17q23-rs6504950 (COX11), 3p24-rs4973768 (SLC4A7), CASP8-rs17468277, TGFB1-rs1982073 and ESR1-rs3020314). Interactions were tested for by fitting logistic regression models including per-allele and linear trend main effects for SNPs and risk factors, respectively, and single-parameter interaction terms for linear departure from independent multiplicative effects. RESULTS: These analyses were applied to data for up to 26,349 invasive breast cancer cases and up to 32,208 controls from 21 case-control studies. No statistical evidence of interaction was observed beyond that expected by chance. Analyses were repeated using data from 11 population-based studies, and results were very similar. CONCLUSIONS: The relative risks for breast cancer associated with the common susceptibility variants identified to date do not appear to vary across women with different reproductive histories or body mass index (BMI). The assumption of multiplicative combined effects for these established genetic and other risk factors in risk prediction models appears justified.RIGHTS : This article is licensed under the BioMed Central licence at http://www.biomedcentral.com/about/license which is similar to the 'Creative Commons Attribution Licence'. In brief you may : copy, distribute, and display the work; make derivative works; or make commercial use of the work - under the following conditions: the original author must be given credit; for any reuse or distribution, it must be made clear to others what the license terms of this work are