Early menstrual characteristics associated with subsequent diagnosis of endometriosis.

OBJECTIVE: The aim of this study was to investigate the association between early menstrual characteristics, before symptom onset, and later diagnosis of endometriosis. STUDY DESIGN: This was a case-control study of 268 Australian women with surgically confirmed moderate-to-severe endometriosis (cases) and 244 women without endometriosis (controls). Early menstrual cycle characteristics, before age at symptom onset, were analyzed. RESULTS: Menarche after age 14 years was strongly and inversely associated with endometriosis (odds ratio, 0.3; 95% confidence interval, 0.1-0.6). A history of dysmenorrhea was associated with subsequent endometriosis (odds ratio, 2.6; 95% confidence interval, 1.1-6.2). Despite a suggestive trend, shorter menstrual cycle length was not associated with endometriosis. Duration of natural menstruation and heaviness of flow were not associated with subsequent risk of endometriosis; neither was the reported type of sanitary protection used nor history of sexual intercourse during menstruation. CONCLUSION: There is a decreased risk of endometriosis with late age at menarche and an increased risk in women who report an early history of dysmenorrhea.

Clinical outcomes associated with bevacizumab-containing treatment of metastatic colorectal cancer: the BRiTE observational cohort study.

BACKGROUND: The Bevacizumab Regimens' Investigation of Treatment Effects (BRiTE) study is a prospective, observational cohort study designed to elucidate safety and effectiveness outcomes associated with bevacizumab combined with chemotherapy as used in clinical practice for first-line treatment of metastatic colorectal cancer (mCRC). PATIENTS AND METHODS: Baseline characteristics, prespecified bevacizumab-related adverse events, and effectiveness data were collected from 1,953 mCRC patients who were receiving first-line treatment including bevacizumab at 248 U.S. sites. RESULTS: At database lock, the median follow-up was 20.1 months. At baseline, 46% of patients were aged >or=65 years and 49% had an Eastern Cooperative Oncology Group performance status score >or=1. Fluorouracil, leucovorin, and oxaliplatin was the most common first-line chemotherapy regimen (56%). Overall rates of bevacizumab-related adverse events in the BRiTE study, such as gastrointestinal perforation (1.9%), arterial thromboembolic events (2%), grade 3-4 bleeding (2.2%), and de novo hypertension requiring medication (22%), were consistent with those reported in randomized clinical trials (RCTs) of bevacizumab in first-line mCRC treatment. The median progression-free survival (PFS) and overall survival (OS) times were 9.9 (95% confidence interval [CI], 9.5-10.3) months and 22.9 (95% CI, 21.9-24.4) months, respectively. CONCLUSION: The median PFS and OS durations and safety profile of bevacizumab in the BRiTE study were similar to those in RCTs of bevacizumab plus chemotherapy in first-line mCRC patients. The observations from the BRiTE study complement and expand upon RCT data, providing clinical information in a large cohort of bevacizumab-treated patients and subgroups such as the elderly.

Incomplete pregnancy and risk of ovarian cancer: results from two Australian case-control studies and systematic review.

Although full-term pregnancies reduce the risk of ovarian cancer, it has not been conclusively established whether incomplete pregnancies also influence risk. We investigated the relationship between a history of incomplete pregnancy and incident epithelial ovarian cancer among over 4,500 women who participated in two large Australian population-based case-control studies in 1990-1993 and 2002-2005. They provided responses to detailed questions about their reproductive histories and other personal factors. Summary odds ratios (OR) and confidence intervals (CI) derived for each study using the same covariates were aggregated. We found no significant associations between the number of incomplete pregnancies and ovarian cancer, for parous (OR = 0.98, 95% CI: 0.89, 1.08) or nulliparous (OR = 1.06, 95% CI: 0.75, 1.48) women, nor for the number of spontaneous or induced abortions and ovarian cancer for parous women (OR = 0.95, 95% CI 0.82, 1.09; OR = 1.08, 95% CI: 0.86, 1.36) or nulliparous women (OR = 1.2, 95% CI: 0.6, 2.4; OR = 0.8, 95% CI: 0.47, 1.38), respectively. A systematic review of 37 previous studies of the topic confirmed our findings that a history of incomplete pregnancy does not influence a woman's risk of epithelial ovarian cancer.

Varying etiologies lead to different molecular changes in Australian and South African hepatocellular carcinomas.

There is significant regional variation in the etiologic agents responsible for hepatocellular carcinoma (HCC), which influences the genetic and epigenetic mechanisms of malignant transformation. The aim of the present study was to investigate the prevalence of allelic imbalance (AI) and CpG island methylation in HCCs from Australia and South Africa. Genomic DNA was extracted from malignant and non-malignant liver from 37 Australian and 24 South African HCCs and histologically normal liver from 20 transplant donors. AI was examined at 1p, 4p, 4q, 8p, 9p, 13q, 16q and 17p, using 23 microsatellite markers. Methylation status of p14, p16, p15, RIZ1, E-cadherin and O6-MGMT was examined using methylation specific PCR, while MINTs 1, 2, 12, 25 and 31 were assessed using combined bisulfite restriction analysis. The highest prevalence of AI was observed at 9p (69%) and 17p (52%). AI was significantly higher in South African HCCs (p<0.05). The prevalence of promoter methylation of the six genes was significantly higher in Australian cases in both malignant and non-malignant liver tissue (p<0.05). MINT assays revealed an increasing degree of CpG island methylation in the progression of hepatocarcinogenesis which was significant for MINTs 1, 12 and 31 (p<0.05). MINT methylation was more prominent in Australian HCCs. These data indicate that methylation is an early event preceding malignant transformation. Methylation was more and AI less prevalent in Australian than South African HCCs. These data suggest that there are different mechanisms of malignant transformation in HCCs from Australia and South Africa.

Assessment of hepatic steatosis: comparison of quantitative and semiquantitative methods in 108 liver biopsies.

BACKGROUND: There is growing interest in the role of hepatic steatosis in liver injury. The current standard for steatosis assessment is histological grading, although there is variability in the scoring systems used. AIMS: The aim of this study was to compare steatosis assessment by image analysis and histological grading. METHODS: Three methods were used to measure steatosis: histological grading (from 0 to 4); estimation of the percentage of hepatocytes (to nearest 5%) with steatosis; and computer-assisted image analysis. Image analysis was performed on multiple fields for each biopsy with image pro plus 4.5, with steatotic droplets identified on the basis of shape, colour and size. Computer-selected objects were reviewed to ensure that these were steatotic droplets. The predictive accuracy of the three techniques was assessed using measures of obesity and insulin resistance (homeostasis model assessment) as the outcome variables. RESULTS: There was a strong correlation between the results of image analysis and histological grade (r(s)=0.89, P<0.01), and estimated per cent steatosis (r(s)=0.93, P<0.01). The variability in the area of steatosis calculated by image analysis in different fields of a biopsy correlated with the total steatosis area (r(s)=0.93, P<0.01). CONCLUSIONS: Image analysis did not offer any additional predictive value when the association between degree of obesity or insulin resistance was correlated with the different methods of assessing steatosis. Image analysis allows measurement of area of steatosis in liver biopsy material and generates a continuous variable that facilitates statistical analysis. These aspects may prove beneficial in research settings.

Bevacizumab beyond first progression is associated with prolonged overall survival in metastatic colorectal cancer: results from a large observational cohort study (BRiTE).

PURPOSE: Bevacizumab provides a survival benefit in first- and second-line metastatic colorectal cancer (mCRC). In a large, observational, bevacizumab treatment study (Bevacizumab Regimens: Investigation of Treatment Effects and Safety [BRiTE]) in patients who had mCRC, a longer-than-expected overall survival (OS) of 25.1 months was reported. The association between various pre- and post-treatment factors (including the use of bevacizumab beyond first progression [BBP]) and survival was examined. PATIENTS AND METHODS: The 1,445 of 1,953 previously untreated patients with mCRC who were enrolled in BRiTE and who experienced disease progression (PD) were classified into three groups: no post-PD treatment (n = 253), post-PD treatment without bevacizumab (no BBP; n = 531), and BBP (n = 642). Relevant baseline and on-study variables, including BBP, were analyzed with a Cox model with respect to their independent effect on survival beyond first PD. RESULTS: Median OS was 25.1 months (95% CI, 23.4 to 27.5 months), and median progression-free survival was 10.0 months in the overall BRiTE population. Baseline and postbaseline factors were well balanced between the BBP and no-BBP groups. Median OS rates were 12.6, 19.9, and 31.8 months in the no post-PD treatment, no-BBP, and BBP groups, respectively. In multivariate analyses, compared with no BBP, BBP was strongly and independently associated with improved survival (HR, 0.48; P < .001). Hypertension that required medication was the only bevacizumab-related safety event that occurred more frequently in the BBP group (24.6% v 19.2%). CONCLUSION: These results from a large, prospective, observational study suggest that continued vascular endothelial growth factor inhibition with bevacizumab beyond initial PD could play an important role improving the overall success of therapy for patients who have mCRC.

Magnetic resonance imaging and spectroscopy for monitoring liver steatosis.

PURPOSE: To compare noninvasive MRI and magnetic resonance spectroscopy (MRS) methods with liver biopsy to quantify liver fat content. MATERIALS AND METHODS: Quantification of liver fat was compared by liver biopsy, proton MRS, and MRI using in-phase/out-of-phase (IP/OP) and plus/minus fat saturation (+/-FS) techniques. The reproducibility of each MR measure was also determined. An additional group of overweight patients with steatosis underwent hepatic MRI and MRS before and after a six-month weight-loss program. RESULTS: A close correlation was demonstrated between histological assessment of steatosis and measurement of intrahepatocellular lipid (IHCL) by MRS (r(s) = 0.928, P < 0.0001) and MRI (IP/OP r(s) = 0.942, P < 0.0001; FS r(s) = 0.935, P < 0.0001). Following weight reduction, four of five patients with >5% weight loss had a decrease in IHCL of >or=50%. CONCLUSION: These findings suggest that standard MRI protocols provide a rapid, safe, and quantitative assessment of hepatic steatosis. This is important because MRS is not available on all clinical MRI systems. This will enable noninvasive monitoring of the effects of interventions such as weight loss or pharmacotherapy in patients with fatty liver diseases.

Recognition of genetic factors influencing the progression of hepatitis C : potential for personalized therapy.

Infection with hepatitis C virus (HCV) is a major cause of chronic liver disease. Hepatic fibrosis may develop in subjects with chronic HCV infection, culminating in cirrhosis and an increased risk of hepatocellular carcinoma. The rate of development of fibrosis varies substantially between individuals; while it is influenced by a number of demographic and environmental factors, these account for only a small proportion of the variability. There are no clinical markers or tests that predict the rate of fibrosis progression in an individual subject. Thus, there has been increasing interest in the influence of host genetic factors on the rate of disease progression, and whether a genetic signature can be developed to reliably identify individuals at risk of severe disease. Numerous case-control, candidate gene, allele-association studies have examined the relationship between host single nucleotide polymorphisms or other genetic mutations and fibrosis in patients with chronic HCV infection. However, these studies have generally been irreproducible and disappointing. As seen with genetic studies for other diseases, small study cohorts and poor study design have contributed to limited meaningful findings. The successful determination of genetic signatures for fibrosis progression in chronic HCV will require multicenter collaborations using genome-wide association studies, with large, phenotypically well-defined sample sets. While these studies will require a significant financial commitment, a successful outcome offers the potential for personalized therapy and better patient management.

Body size and risk of epithelial ovarian and related cancers: a population-based case-control study.

Different subtypes of ovarian cancer appear to have different causes; however, the association between body mass index (BMI) and the different subtypes is unclear. We examined the associations between body-mass index (BMI) and weight gain and risk of the different histological subtypes of epithelial ovarian cancer in a case-control study in Australia. Cases aged 18-79 with a new diagnosis of invasive epithelial ovarian cancer (n = 1,269) or borderline tumor (n = 311) were identified through a network of clinics and cancer registries throughout Australia. Controls (n = 1,509) were selected from the Electoral Roll. Height and weight (1 year previously, at age 20 and maximum weight) and other risk factor information were ascertained via a self-administered questionnaire. Obesity was positively associated with clear cell tumors (Odds Ratio 2.3; 95% confidence interval 1.2-4.2) but not invasive endometrioid or mucinous tumors. Although there was no association with invasive serous tumors overall (0.9; 0.7-1.2), we did see an increased risk of serous peritoneal tumors (2.9; 1.7-4.9), but not of serous tumors of the ovary and fallopian tube. Of the borderline subtypes, obesity was positively associated with serous (1.8; 1.1-2.8) but not mucinous tumors (1.1; 0.7-1.7). Overweight was not associated with any subtype overall. There was no association with BMI at age 20, or weight gain for any of the histological subtypes. These results add to the current evidence that obesity increases a woman's risk of developing distinct histological subtypes of ovarian cancer.

Dietary patterns and risk of ovarian cancer in the California Teachers Study cohort.

Previous studies have examined the association between individual foods or nutrients, but not overall diet, and ovarian cancer risk. To account for the clustering of foods in the diet, we investigated the association between dietary patterns and risk of ovarian cancer in the prospective California Teachers Study cohort. Of 97,292 eligible women who completed the baseline dietary assessment in 1995-1996, 311 women developed epithelial ovarian cancer on or before December 31, 2004. Based on principal components analysis, 5 major dietary patterns were identified and termed plant-based, high-protein/high-fat, high-carbohydrate, ethnic, and salad-and-wine. Multivariable Cox proportional hazards regression analysis was used to estimate associations between these dietary patterns and risk of incident ovarian cancer. Most of the dietary patterns were not significantly associated with ovarian cancer risk. However, women who followed a plant-based diet had higher risk; comparing those in the top quintile of plant-based food intake with those in the lowest quintile, the relative risk of ovarian cancer was 1.65 (95% confidence interval = 1.07-2.54; P(trend) = 0.03). Associations with the 5 dietary patterns did not vary by known ovarian cancer risk factors or other behavioral or sociodemographic characteristics. Overall, our results show no convincing associations between dietary patterns and ovarian cancer risk.

Population health and clinical data linkage: the importance of a population registry.

OBJECTIVE: The Australian National Collaborative Research Infrastructure Strategy supports development of a national research capability in population health and clinical data linkage. This paper illustrates the importance of incorporating a population registry within such a system using an example provided by the Manitoba Injury Outcome Study (MIOS) that quantified the long-term burden of mortality attributable to injury in working-age adults. METHODS: MIOS is a population-based matched cohort study that used administrative health data from Manitoba, Canada. An inception cohort of injured cases (ICD-9-CM 800-995) aged 18-64 years was identified from all Manitoba hospital admissions between 1988 and 1991. A matched non-injured comparison group was randomly selected from the total provincial population using the Manitoba Population Registry. Mortality outcomes were obtained by linking the two cohorts with the deaths data over 10 years. Mortality rate ratios (MRRs) were calculated to compare the injured and non-injured cohorts. RESULTS: A total of 21,032 matched pairs were identified. Using the population registry, the 10-year adjusted all-cause MRR comparing injured and non-injured cohort was 1.80 (95% CI 1.65-1.98). Without the registry, the unadjusted standardised morality ratio was 2.76 (95% CI 2.52-3.02). CONCLUSIONS: The effect of injury on mortality outcomes was over-estimated using only the injured cases, without use of the population registry. Use of the population registry enabled the selection of a matched non-injured group for comparison purposes, ensured comprehensive follow-up of almost all participants, and provided more accurate estimates of exposure time, incidence of mortality and relative risk.

Progressive fibrosis in nonalcoholic steatohepatitis: association with altered regeneration and a ductular reaction.

BACKGROUND & AIMS: Portal fibrosis and linkage is a key feature of progressive disease in nonalcoholic steatohepatitis (NASH), but not simple steatosis. It is underappreciated and poorly understood. Fatty liver has impaired regeneration that induces a secondary replicative pathway using bipotential, periportal, hepatic progenitor cells (HPCs). We propose that activation of this pathway, with increased cell injury in NASH, also induces a periportal ductular reaction (DR) that could produce a profibrogenic stimulus. METHODS: Biopsy specimens from 107 patients with nonalcoholic fatty liver disease and 11 controls were immunostained with cytokeratin-7 to quantify the DR and HPCs, and with p21 to assess hepatocyte replicative arrest. These results were correlated with clinicopathologic variables. RESULTS: Patients with nonalcoholic fatty liver disease had expansion of HPCs, with a strong association between HPCs and the DR (r(s) = 0.582, P < .0001). In those with NASH (n = 69) there was an increased DR compared with simple steatosis, which correlated with the stage of fibrosis (r(s) = 0.510, P < .0001). The DR increased with the grade of NASH activity (r(s) = 0.478, P < .0001), grade of portal inflammation (r(s) = 0.445, P < .0001), and extent of hepatocyte replicative arrest (r(s) = 0.446, P < .0001). Replicative arrest was in turn associated with insulin resistance (r(s) = 0.450, P < .0001) and NASH activity (r(s) = 0.452, P < .0001). By multivariate analysis, the extent of DR (odds ratio [OR] = 17.9, P = .016), hepatocyte ballooning (OR = 8.1, P < .0001), and portal inflammation (OR = 3.3, P = .005) were associated independently with fibrosis. CONCLUSIONS: These findings suggest that an altered replication pathway in active NASH promotes a periportal DR, which in turn may provoke progressive periportal fibrogenesis.

Scald prevention campaigns: do they work?

The aim of this study was to quantify the effectiveness of the Queensland "Hot Water Burns Like Fire" campaign. Cross-section temperature sampling of households' bathroom hot water taps was conducted in Brisbane in 1990 before the intervention (n = 872) and in 2002 to 2003 after the intervention (n = 871). In both surveys, temperature was measured with thermometers held under running water from the bathroom hot tap until the reading stabilized (2 minutes). In 2002 to 2003 the interviewer also recorded whether or not the householder believed a tempering valve was installed in the home. The main injury outcome measure was all scald injury-related admissions at hospitals in Queensland from July 1990 to June 2003. The difference between the mean hot water tap temperature in 1990 and in 2002 to 2003 was determined with independent sample t-tests (P < .05). Rates of hospital admissions were grouped into two categories: scald injuries per year prior to the introduction of the hot water tempering valve legislation (April 1998) and scald injuries per year post-legislation. The difference between the preintervention and postintervention mean rates was determined with t-tests (P < .05). Additionally, the rates were plotted on a scatter plot by year, and a linear regression analysis was used to quantify the relationship with rates of scald-related injuries and year. The temperature in homes where the occupants reported having a tempering valve (mean = 55.5 degrees C) was significantly lower than in homes whose occupants reported not having a tempering valve (mean = 60.1 degrees C) or did not know whether they had a tempering valve (mean = 61.8 degrees C) (P < .01). However, the comparison of the hot water temperature between 1990 and 2002 to 2003 showed a significantly higher mean hot water temperature in 2002 to 2003 (P < .01). There was a significantly higher mean scald injury rate after the introduction of the "Hot Water Burns Like Fire" campaign (170.36/100,000) than before (113.41/100,000; P = .01). The linear regression line of best fit of these data has a slope of 10.43 (P < .01) and an r of 0.79. The results of this study suggest that the Queensland "Hot Water Burns Like Fire" campaign has not led to a significant reduction in hot water temperature or scald injury rates. The lack of effect identified in this study provides further evidence of the strong need to conduct rigorous evaluations of all major health promotion campaigns to add to the evidence base for such activities.

Diet and risk of ovarian cancer in the California Teachers Study cohort.

Dietary phytochemical compounds, including isoflavones and isothiocyanates, may inhibit cancer development but have not yet been examined in prospective epidemiologic studies of ovarian cancer. The authors have investigated the association between consumption of these and other nutrients and ovarian cancer risk in a prospective cohort study. Among 97,275 eligible women in the California Teachers Study cohort who completed the baseline dietary assessment in 1995-1996, 280 women developed invasive or borderline ovarian cancer by December 31, 2003. Multivariable Cox proportional hazards regression, with age as the timescale, was used to estimate relative risks and 95% confidence intervals; all statistical tests were two sided. Intake of isoflavones was associated with lower risk of ovarian cancer. Compared with the risk for women who consumed less than 1 mg of total isoflavones per day, the relative risk of ovarian cancer associated with consumption of more than 3 mg/day was 0.56 (95% confidence interval: 0.33, 0.96). Intake of isothiocyanates or foods high in isothiocyanates was not associated with ovarian cancer risk, nor was intake of macronutrients, antioxidant vitamins, or other micronutrients. Although dietary consumption of isoflavones may be associated with decreased ovarian cancer risk, most dietary factors are unlikely to play a major role in ovarian cancer development.

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.

Prevalence and risk factors for lifetime exposure to Pap smear abnormalities in the Australian community.

BACKGROUND: This study examined the prevalence, correlates and consequences of abnormal Pap smears in a population-based survey of sexuality and health in the Australian community. METHODS: Cross-sectional telephone survey of 908 women aged 18-59 years randomly selected from the Commonwealth electoral roll. RESULTS: Most women (91%) reported having had at least one Pap smear test, a figure directly comparable with national estimates. Being single (prevalence ratio (PR) 4.61; 95% CI 2.09-10.17) and not having had sexual intercourse (PR 5.31, 95% CI 3.11-9.07) were strong predictors of never having been tested. One in four women (26%) who reported being screened also reported having had an abnormal Pap smear result, of whom 66% said they had further testing and 52% some form of treatment. A minority (19%) reported negative effects of treatment on their sex lives. Having been diagnosed with human papillomavirus (HPV) (PR 2.87, 95% CI 1.84-4.48), and to a lesser degree, having had a greater number of male sexual partners (PR 1.38, 95% CI 1.01-1.89), and experiencing sexual problems in the last year (PR 0.99, 95% CI 0.99-1.88) were independently associated with reporting of abnormal Pap smear results. CONCLUSIONS: Approximately one in four women self report lifetime exposure to Pap smear abnormalities. It is important that women are well prepared for this common experience. A causal association between multiple sexual partners and risk of acquiring HPV infection is supported by these data.

Does smoking increase risk of ovarian cancer? A systematic review.

OBJECTIVES: Although early reports suggested that smoking was not associated with ovarian cancer risk, recent studies have reported positive associations for cancers of the mucinous subtype. We sought to clarify the relationship between smoking and ovarian cancer by histological subtype. METHODS: We conducted a systematic literature review and meta-analysis of studies investigating the association between smoking and risk of the different histological subtypes of epithelial ovarian cancer. Eight population-based case-control studies, one pooled analysis of case-control studies, and one cohort study met the inclusion criteria. Summary relative risks (RR), 95% confidence intervals (CI), and tests for heterogeneity were generated from random effects models. RESULTS: Combined, these studies included a total of 910 women with mucinous and 5564 with non-mucinous ovarian cancers. There was a significant doubling of risk of mucinous ovarian cancer in current smokers compared to never smokers (summary RR 2.1, 95% CI 1.7-2.7), but no increased risk of serous (1.0, 95% CI 0.8-1.2) or endometrioid (0.8, 95% CI 0.6-1.1) cancers and a significant risk reduction for clear cell cancers (0.6, 95% CI 0.3-0.9). The risk of mucinous cancer increased with increasing amount smoked but returned to that of never smokers within 20-30 years of stopping smoking. CONCLUSIONS: Meta-analysis suggests that current smoking doubles a woman's risk of developing mucinous ovarian cancer. Stopping smoking returns the risk to normal in the long term. Smoking may thus be one of the few modifiable factors offering potential for primary prevention of mucinous ovarian cancer.

Repeatability of self-reported information for population-based studies of cancer.

PURPOSE: To measure the repeatability of a cancer risk factor questionnaire in a population-based case-control study. METHODS: Questionnaires were completed on two occasions by patients with cancer of the ovary (n=25) or esophagus (n=23) and by 37 controls without cancer. We assessed general cancer risk factors including height and weight (for calculating body mass index (BMI)), smoking and anti-inflammatory (NSAID) use. Risk factors specific for ovarian and esophageal cancers were also assessed. Agreement was measured by the correlation coefficient and weighted kappa statistic (kw) for continuous and categorical variables respectively. RESULTS: We observed very high levels of agreement for BMI (kw=0.84) and smoking history, including ages at initiation and quitting (Pearson correlation = 0.87 and 0.86 respectively). There was moderate to substantial agreement for use of anti-inflammatory drugs (aspirin kw =0.52, other NSAIDS kw =0.72). Agreement for lifetime prevalence of medical conditions varied from almost perfect (e.g. history of benign breast disease (k =0.86)) to moderate (e.g. heartburn (k =0.57)). Item repeatability was not materially altered by case-control status, age or sex of respondents or interval between completions. CONCLUSIONS: Self-reported cancer risk factor information demonstrates moderate to almost perfect levels of agreement, suggesting these items are suitable for risk estimation and epidemiologic inference.

Population attributable risk of breast cancer in white women associated with immediately modifiable risk factors.

BACKGROUND: Estrogen/progestin replacement therapy (EPRT), alcohol consumption, physical activity, and breast-feeding duration differ from other factors associated with breast cancer in being immediately modifiable by the individual, thereby representing attractive targets for future breast cancer prevention efforts. To justify such efforts, it is vital to quantify the potential population-level impacts on breast cancer considering population variations in behavior prevalence, risk estimate, and baseline incidence. METHODS: For each of these four factors, we calculated population attributable risk percents (PARs) using population-based survey (2001) and cancer registry data (1998-2002) for 41 subpopulations of white, non-Hispanic California women aged 40-79 years, and ranges of relative risk (RR) estimates from the literature. RESULTS: Using a single RR estimate, subpopulation PARs ranged from 2.5% to 5.6% for hormone use, from 0.0% to 6.1% for recent consumption of > or = 2 alcoholic drinks daily, and 4.6% to 11.0% for physical inactivity. Using a range of RR estimates, PARs were 2-11% for EPRT use, 1-20% for alcohol consumption and 2-15% for physical inactivity. Subpopulation data were unavailable for breastfeeding, but PARs using published RR estimates ranged from 2% to 11% for lifetime breastfeeding > or = 31 months. Thus, of 13,019 breast cancers diagnosed annually in California, as many as 1,432 attributable to EPRT use, 2,604 attributable to alcohol consumption, 1,953 attributable to physical inactivity, and 1,432 attributable to never breastfeeding might be avoidable. CONCLUSION: The relatively feasible lifestyle changes of discontinuing EPRT use, reducing alcohol consumption, increasing physical activity, and lengthening breastfeeding duration could lower population breast cancer incidence substantially.

Injury severity: role of alcohol, substance use and risk-taking.

OBJECTIVE: The objective of the present study was to quantify the relationship between acute alcohol consumption and injury severity. METHODS: A cross-sectional study was conducted at the Gold Coast Hospital, Gold Coast, Queensland, Australia between October 2000 and October 2001. Data were collected from a systematic sample of patients greater than 15 years of age who presented to the ED for treatment of an injury sustained less than 24 h prior to presentation. Study participants were interviewed face to face on-site. Information obtained included: demographics details; situational variables relative to time of injury (i.e. location, activity and companions at time of injury); self-reported alcohol consumption in the 6 and 24 h prior to time of injury; usual alcohol consumption patterns; self-reported substance use in the 6 and 24 h prior to time of injury; and risk-taking behaviour. Injury severity was coded from patient medical records using the New Injury Severity Score. RESULTS: Of 789 eligible patients presenting during the study periods, 593 were interviewed (75.2%). Patients who reported drinking above low-risk levels (odds ratio [OR] = 3.35; 95% confidence interval [CI] 1.2-9.6) or who drank beer (OR = 3.54; 95% CI 1.1-11.1) in 6 h prior to injury were significantly more likely to sustain serious than minor injury. Drinking setting and usual drinking patterns were not significantly associated with injury severity, either in crude analyses, or after adjusting for relevant variables. CONCLUSION: The results of the present study support the conclusion that among injured patients who presented for treatment at a large metropolitan ED, although acute alcohol consumption does not appear to be associated with minor or moderate injury, there is some evidence to suggest that acute alcohol consumption is associated with serious injury.