The associations of CD4 count, CD4/CD8 ratio, and HIV viral load with survival from non-small cell lung cancer in persons living with HIV.

HIV status may influence survival from non-small cell lung cancer (NSCLC). Among NSCLC patients in the Bronx, NY, we assessed (1) associations of CD4 count, CD4/CD8 ratio and HIV viral load (VL) with survival and (2) prognostic factors among persons living with HIV (PLWH). We compared survival from NSCLC diagnosis (2004-2017) between HIV-negative persons (HIV-, n=2,881) and PLWH (n=88) accounting for clinical and sociodemographic factors. HIV-survival was also compared with PLWH, dichotomized by CD4 (<200 vs. ≥200cells/µL), CD4/CD8 (median, <0.43 vs. ≥0.43) and VL (<75 vs. ≥75copies/mL) at NSCLC diagnosis. Among PLWH, we assessed the relationships of CD4, CD4/CD8, and VL with survival, adjusting for age, sex, and cancer stage. PLWH with CD4< 200cells/µL had lower survival than HIV- [hazard ratio, 95% confidence interval [HR(95%CI)]=1.86(0.98-3.55)]. Survival was similar between PLWH with CD4≥ 200cells/µL and HIV- [HR(95%CI) = 0.90(0.61-1.33)]. Results were similar when categorizing PLWH by CD4/CD8 [vs. HIV-: low CD4/CD8: HR(95%CI) = 1.74(1.07-3.89); high CD4/CD8: HR(95%CI) = 0.63(0.37-1.07)] and VL [vs. HIV-: <75copies/mL: HR(95%CI) = 0.74(0.46-1.21), ≥75copies/mL: HR(95%CI) = 1.41(0.88-2.27)]. Among PLWH, CD4< 200cells/µL was associated with worse survival [vs. CD4≥ 200cells/µL: HR(95%CI) = 2.37(1.14-4.92)]. CD4, CD4/CD8, and VL may be prognostic markers for PLWH with NSCLC, suggesting immune status may be important in NSCLC survival among PLWH.

Metabolic phenotypes of obesity: frequency, correlates and change over time in a cohort of postmenopausal women.

OBJECTIVE: The possibility that a subset of persons who are obese may be metabolically healthy-referred to as the 'metabolically healthy obese' (MHO) phenotype-has attracted attention recently. However, few studies have followed individuals with MHO or other obesity phenotypes over time to assess change in their metabolic profiles. The aim of the present study was to examine transitions over a 6-year period among different states defined simultaneously by body mass index (BMI) and the presence/absence of the metabolic syndrome (MetS). METHODS: We used repeated measurements available for a subcohort of participants enrolled in the Women's Health Initiative (N=3512) and followed for an average of 6 years to examine the frequency of different metabolic obesity phenotypes at baseline, the 6-year transition probabilities to other states and predictors of the risk of different transitions. Six phenotypes were defined by cross-tabulating BMI (18.5-<25.0, 25.0-<30.0, ⩾30.0 kg m-2) by MetS (yes, no). A continuous-time Markov model was used to estimate 6-year transition probabilities from one state to another. RESULTS: Over the 6 years of follow-up, one-third of women with the healthy obese phenotype transitioned to the metabolically unhealthy obese (MUO) phenotype. Overall, there was a marked tendency toward increased metabolic deterioration with increasing BMI and toward metabolic improvement with lower BMI. Among MHO women, the 6-year probability of becoming MUO was 34%, whereas among unhealthy normal-weight women, the probability of 'regressing' to the metabolically healthy normal-weight phenotype was 52%. CONCLUSIONS: The present study demonstrated substantial change in metabolic obesity phenotypes over a 6-year period. There was a marked tendency toward metabolic deterioration with greater BMI and toward metabolic improvement with lower BMI.

Dairy products and pancreatic cancer risk: a pooled analysis of 14 cohort studies.

Pancreatic cancer has few early symptoms, is usually diagnosed at late stages, and has a high case-fatality rate. Identifying modifiable risk factors is crucial to reducing pancreatic cancer morbidity and mortality. Prior studies have suggested that specific foods and nutrients, such as dairy products and constituents, may play a role in pancreatic carcinogenesis. In this pooled analysis of the primary data from 14 prospective cohort studies, 2212 incident pancreatic cancer cases were identified during follow-up among 862 680 individuals. Adjusting for smoking habits, personal history of diabetes, alcohol intake, body mass index (BMI), and energy intake, multivariable study-specific hazard ratios (MVHR) and 95% confidence intervals (CIs) were calculated using the Cox proportional hazards models and then pooled using a random effects model. There was no association between total milk intake and pancreatic cancer risk (MVHR = 0.98, 95% CI = 0.82-1.18 comparing ≥500 with 1-69.9 g/day). Similarly, intakes of low-fat milk, whole milk, cheese, cottage cheese, yogurt, and ice-cream were not associated with pancreatic cancer risk. No statistically significant association was observed between dietary (MVHR = 0.96, 95% CI = 0.77-1.19) and total calcium (MVHR = 0.89, 95% CI = 0.71-1.12) intake and pancreatic cancer risk overall when comparing intakes ≥1300 with <500 mg/day. In addition, null associations were observed for dietary and total vitamin D intake and pancreatic cancer risk. Findings were consistent within sex, smoking status, and BMI strata or when the case definition was limited to pancreatic adenocarcinoma. Overall, these findings do not support the hypothesis that consumption of dairy foods, calcium, or vitamin D during adulthood is associated with pancreatic cancer risk.

US pediatric population-level associations of DXA-measured percentage of body fat with four BMI metrics with cutoffs.

OBJECTIVE: Four body mass index (BMI) metrics--BMI, BMI z-score, BMI percentile and BMI%--are commonly used as proxy measures for children's adiposity. We sought to determine a BMI metric that is most strongly associated with measured percentage of body fat (%BF) in the US pediatric population stratified by sex, age and race/ethnicity, and to determine cutoffs that maximize the association for each BMI metric. SUBJECTS, DESIGN AND METHODS: %BF was measured by dual-energy X-ray absorptiometry among N=6120 US boys and girls aged 8.0-17.9 years old from the National Health and Nutrition Examination Survey 1999-2004. We fit piecewise linear regression models with cutoffs to %BF data using each BMI metric as the predictor stratified by sex, race/ethnicity and age. The slopes were modeled differently before and after the cutoffs which were determined on the basis of grid searches. RESULTS: BMI z-score was in general most strongly associated with %BF for both boys and girls. The associations of the four BMI metrics were lowest for boys aged 12-13.9 years and girls aged 16-17.9 years, and strongest for Mexican-American boys and for non-Hispanic Black girls. Overall, the associations were stronger for girls than for boys. In boys, BMI had the lowest association with %BF (R(2)=0.39) for all ages combined. The fold changes in slopes before and after cutoffs were greatest in general for BMI percentiles regardless of age, sex and race/ethnicity. BMI z-score cutoffs were 0.4 for both boys and girls for all ages combined. Except for BMI, the slopes after the cutoffs were in general greater than those before. CONCLUSIONS: All BMI metrics were strongly associated with %BF when stratified by age and race/ethnicity except that BMI was the least associated with %BF in boys for all ages combined. Overall, BMI z-score was superior for evaluation of %BF, and its cutoff of 0.4 can also serve as a threshold for careful monitoring of weight status.

Association of anthropometric measures and hemostatic factors in postmenopausal women: a longitudinal study.

BACKGROUND AND AIMS: Obesity has been associated with increased levels of hemostatic factors. However, few studies have compared change in different anthropometric measures of adiposity in relation to change in levels of hemostatic factors. Our aim was to examine prospectively the association of change in body mass index (BMI), waist-hip ratio (WHR), waist circumference (WC), and waist circumference-height ratio (WHtR) with change in markers of hemostasis in a population of postmenopausal women. METHODS AND RESULTS: A subsample of women in the Women's Health Initiative (WHI) cohort had fasting blood samples and anthropometric measurements obtained at multiple time points over 12.8 years of follow-up. Of these, we studied the 2593 women who were not in the intervention arm of any WHI clinical trial. Their blood samples were used to measure plasma fibrinogen, factor VII antigen activity, and factor VII concentration at baseline, and at years 1, 3, and 6. We conducted mixed-effects linear regression analyses to examine the longitudinal association between change in anthropometric factors and change in hemostatic factors, adjusting for a wide range of potential confounding factors. In longitudinal analyses using repeated measures, change in BMI, WC, and WHtR were all positively associated with change in all 3 hemostatic factors. Change in anthropometric variables was most strongly associated with change in fibrinogen. CONCLUSIONS: Our results suggest that an increase in adiposity over time is robustly associated with increased levels of hemostatic factors. Registration number of clinical trial: NCT00000611.

The etiology of uterine sarcomas: a pooled analysis of the epidemiology of endometrial cancer consortium.

BACKGROUND: Uterine sarcomas are characterised by early age at diagnosis, poor prognosis, and higher incidence among Black compared with White women, but their aetiology is poorly understood. Therefore, we performed a pooled analysis of data collected in the Epidemiology of Endometrial Cancer Consortium. We also examined risk factor associations for malignant mixed mullerian tumours (MMMTs) and endometrioid endometrial carcinomas (EECs) for comparison purposes. METHODS: We pooled data on 229 uterine sarcomas, 244 MMMTs, 7623 EEC cases, and 28,829 controls. Odds ratios (ORs) and 95% confidence intervals (CIs) for risk factors associated with uterine sarcoma, MMMT, and EEC were estimated with polytomous logistic regression. We also examined associations between epidemiological factors and histological subtypes of uterine sarcoma. RESULTS: Significant risk factors for uterine sarcoma included obesity (body mass index (BMI)≥30 vs BMI<25 kg m(-2) (OR: 1.73, 95% CI: 1.22-2.46), P-trend=0.008) and history of diabetes (OR: 2.33, 95% CI: 1.41-3.83). Older age at menarche was inversely associated with uterine sarcoma risk (≥15 years vs <11 years (OR: 0.70, 95% CI: 0.34-1.44), P-trend: 0.04). BMI was significantly, but less strongly related to uterine sarcomas compared with EECs (OR: 3.03, 95% CI: 2.82-3.26) or MMMTs (OR: 2.25, 95% CI: 1.60-3.15, P-heterogeneity=0.01). CONCLUSION: In the largest aetiological study of uterine sarcomas, associations between menstrual, hormonal, and anthropometric risk factors and uterine sarcoma were similar to those identified for EEC. Further exploration of factors that might explain patterns of age- and race-specific incidence rates for uterine sarcoma are needed.

Optimal scaling of weight and waist circumference to height for maximal association with DXA-measured total body fat mass by sex, age and race/ethnicity.

BACKGROUND: Body mass index (BMI; weight (Wt)/height (Ht) (in kg m(-2)) and waist circumference (WC) are widely used as proxy anthropometric measures for total adiposity. Little is known about what scaling power of 'x' in both Wt(kg)/Ht(m)(x) and WC(m)/Ht(m)(x) is maximally associated with measured total body fat mass (TBFM). Establishing values for x would provide the information needed to create optimum anthropometric surrogate measures of adiposity. OBJECTIVE: To estimate the value of 'x' that renders Wt/Ht(x) and WC/Ht(x) maximally associated with DXA-measured TBFM. SUBJECTS: Participants of the NHANES 1999-2004 surveys, stratified by sex (men, women), race/ethnicity (non-Hispanic whites, non-Hispanic blacks, Mexican-Americans), and age(18-29, 30-49, 50-84 years). METHODS: We apply a grid search by increasing x from 0.0-3.0 by increments of 0.1 to the simple regression models, TBFM=b0+b1*(Wt/Ht(x)) and TBFM=b0+b1*(WC/Ht(x)) to obtain an estimate of x that results in the greatest R(2), taking into account complex survey design features and multiply imputed data. RESULTS: R(2)'s for BMI are 0.86 for men (N=6544) and 0.92 for women (N=6362). The optimal powers x for weight are 1.0 (R(2)=0.90) for men and 0.8 (R(2)=0.96) for women. The optimal power x for WC is 0, that is, no scaling of WC to height, for men (R(2)=0.90) or women (R(2)=0.82). The optimal powers for weight across nine combinations of race/ethnicity and age groups for each sex vary slightly (x=0.8-1.3) whereas the optimal scaling powers for WC are all 0 for both sexes except for non-Hispanic black men aged 18-29y (x=0.1). Although the weight-for-height indices with optimal powers are not independent of height, they yield more accurate TBFM estimates than BMI. CONCLUSION: In reference to TBFM, Wt/Ht and Wt/Ht(0.8) are the optimal weight-for-height indices for men and women, respectively, whereas WC alone, without Ht adjustment, is the optimal WC-for-height index for both sexes. Thus, BMI, an index independent of height, may be less useful when predicting TBFM.

A longitudinal study of serum insulin and glucose levels in relation to colorectal cancer risk among postmenopausal women.

BACKGROUND: It is unclear whether circulating insulin or glucose levels are associated with increased risk of colorectal cancer. Few prospective studies have examined this question, and only one study had repeated measurements. METHODS: We conducted a prospective study of colorectal cancer risk using the subsample of women in the Women's Health Initiative study whose fasting blood samples, collected at baseline and during follow-up, were analysed for insulin and glucose. Cox proportional hazards models were used to assess associations with colorectal cancer risk in both baseline and time-dependent covariates analyses. RESULTS: Among 4902 non-diabetic women with baseline fasting serum insulin and glucose values, 81 incident cases of colorectal cancer were identified over 12 years of follow-up. Baseline glucose levels were positively associated with colorectal cancer and colon cancer risk: multivariable-adjusted hazard ratio (HR) comparing the highest (≥99.5 mg dl(-1)) with the lowest tertile (<89.5 mg dl(-1)): 1.74, 95% confidence interval (CI) 0.97-3.15 and 2.25, 95% CI: 1.12-4.51, respectively. Serum insulin and homeostasis model assessment were not associated with risk. Analyses of repeated measurements supported the baseline results. CONCLUSION: These data suggest that elevated serum glucose levels may be a risk factor for colorectal cancer in postmenopausal women.

Effect of long term low-fat dietary intervention on change in hemostatic factors: results from the Women's Health Initiative.

Low-fat diet may play a role in prevention of cardiovascular disease (CVD) by altering the levels of hemostatic factors. There are yet limited data on the effects of low-fat diet on the circulating levels of these factors and existing studies are limited by small sample size and short duration of follow-up. We conducted an analysis in a subset of women (active arm = 723; control arm = 1036) within the Women's Health Initiative Dietary Modification Trial to investigate the long term effect of a low-fat diet on circulating levels of fibrinogen, factor VII concentration and factor VII activity among postmenopausal women aged 50-79 years. Using linear mixed effects model with random intercept and data from three follow-up visits (years 1, 3 and 6) we evaluated the change in each factor over time. Overall, the changes in these factors were small (less than 5%) in both the arms of the trials at the end of intervention and there was no significant difference in mean change between the two arms. Our results indicate that the low-fat dietary intervention was not associated with significant changes in hemostatic factors among postmenopausal women.

Circulating sex hormones and breast cancer risk factors in postmenopausal women: reanalysis of 13 studies.

BACKGROUND: Breast cancer risk for postmenopausal women is positively associated with circulating concentrations of oestrogens and androgens, but the determinants of these hormones are not well understood. METHODS: Cross-sectional analyses of breast cancer risk factors and circulating hormone concentrations in more than 6000 postmenopausal women controls in 13 prospective studies. RESULTS: Concentrations of all hormones were lower in older than younger women, with the largest difference for dehydroepiandrosterone sulphate (DHEAS), whereas sex hormone-binding globulin (SHBG) was higher in the older women. Androgens were lower in women with bilateral ovariectomy than in naturally postmenopausal women, with the largest difference for free testosterone. All hormones were higher in obese than lean women, with the largest difference for free oestradiol, whereas SHBG was lower in obese women. Smokers of 15+ cigarettes per day had higher levels of all hormones than non-smokers, with the largest difference for testosterone. Drinkers of 20+ g alcohol per day had higher levels of all hormones, but lower SHBG, than non-drinkers, with the largest difference for DHEAS. Hormone concentrations were not strongly related to age at menarche, parity, age at first full-term pregnancy or family history of breast cancer. CONCLUSION: Sex hormone concentrations were strongly associated with several established or suspected risk factors for breast cancer, and may mediate the effects of these factors on breast cancer risk.

Biomarkers of body iron stores and risk of developing type 2 diabetes.

AIM: Iron may contribute to the pathogenesis of type 2 diabetes mellitus (DM) by inducing oxidative stress and interfering with insulin secretion. Elevated ferritin levels are associated with increased DM risk among healthy individuals. However, it is yet unknown if ferritin predicts DM incidence among high-risk individuals with impaired glucose tolerance (IGT). Furthermore, the association between soluble transferrin receptors (sTfR), a novel marker of iron status, and DM risk has not yet been prospectively investigated in these individuals. We conducted this study to evaluate the association between baseline levels of ferritin and sTfR and the risk of developing DM among overweight and obese individuals at high risk of DM. METHODS: This nested case-control study (280 cases and 280 matched controls) was conducted within the placebo arm of the Diabetes Prevention Program, is a clinical trial conducted among overweight/obese individuals with IGT. Ferritin and sTfR levels were measured by immunoturbidimetric assays. Incident DM was ascertained by annual 75-g oral glucose tolerance test and semi-annual fasting glucose. RESULTS: Compared with controls, cases had higher sTfR levels (3.50 +/- 0.07 vs. 3.30 +/- 0.06 mg/l; p = 0.03), but ferritin levels were not statistically different. The multivariable odds ratios (OR) and 95% confidence intervals (95% CI) for DM incidence comparing highest with the lowest quartiles of sTfR was 2.26 (1.37-4.01) (p-trend: 0.008). CONCLUSIONS: Modestly elevated sTfR levels are associated with increased DM risk among overweight and obese individuals with IGT. Future studies should evaluate factors determining sTfR levels and examine if interventions that lower body iron stores reduce DM incidence.

Dietary intake of selected B vitamins in relation to risk of major cancers in women.

Although folic acid has been investigated for its potential to inhibit carcinogenesis, few epidemiologic studies have assessed the effects of intake of thiamin, riboflavin, and niacin, which may reduce cancer risk by acting as cofactors in folate metabolism or by other mechanisms. Using data from a large cohort of Canadian women, we examined the association of dietary intake of these nutrients, as well as intake of folate, methionine, and alcohol, with cancers of the breast, endometrium, ovary, colorectum, and lung ascertained during an average of 16.4 years of follow-up. After exclusions, the following numbers of incident cases were available for analysis: breast, n=2491; endometrium, n=426; ovary, n=264; colorectum, n=617; and lung, n=358. Cox proportional hazard models were used to estimate risk of each cancer with individual nutrients and to explore possible effect modification by combinations of nutrients on cancer risk. Few significant associations of intake of individual B vitamins with the five cancers were observed. Alcohol consumption showed a modest positive association with breast cancer risk but not with risk of the other cancers. There was no evidence of effect modification among the nutrients. This large study provides little support for an association of dietary intake thiamin, riboflavin, niacin, folate, or methionine with five major cancers in women.

Immunohistochemical detection of c-erbB-2 and p53 in benign breast disease and breast cancer risk.

BACKGROUND: We studied the associations between c-erbB-2 protein overexpression and p53 protein accumulation in benign breast tissue and the risk of subsequent breast cancer. METHODS: We conducted a case-control study nested within the cohort of 4888 women in the National Breast Screening Study (NBSS) who were diagnosed with benign breast disease during active follow-up. Case subjects were the women who subsequently developed breast cancer (ductal carcinoma in situ [DCIS] or invasive carcinoma). Control subjects were matched to each case subject on NBSS study arm, screening center, year of birth, and age at diagnosis of benign breast disease. Histologic sections of benign and cancerous breast tissues were analyzed immunohistochemically. Information on potential confounding factors was obtained by use of a self-administered lifestyle questionnaire. RESULTS: Accumulation of p53 protein was associated with an increased risk of progression to breast cancer (adjusted odds ratio [OR] = 2.55; 95% confidence interval [CI] = 1.01-6.40), whereas c-erbB-2 protein overexpression was not (adjusted OR = 0.65; 95% CI = 0.27-1.53). The findings for c-erbB-2 and p53 did not differ among strata defined by menopausal status, allocation within the NBSS, history of breast disease, and whether the benign breast disease was detected at a scheduled screen or between screens. The results were also similar after exclusion of case subjects whose diagnosis of breast cancer occurred within 1 year of their diagnosis of benign breast disease and after exclusion of subjects with DCIS. CONCLUSIONS: p53 protein accumulation, but not c-erbB-2 protein overexpression, appears to be associated with an increased risk of progression to breast cancer in women with benign breast disease.

A case-control study of diet and benign proliferative epithelial disorders of the breast.

Benign proliferative epithelial disorders (BPED) of the breast are conditions which, although not proven precursors of breast cancer, are strongly associated with increased risk of this disease. In a case-control study conducted in Adelaide, South Australia, we investigated the association between dietary factors and risk of BPED. The study involved 383 cases of biopsy-confirmed BPED, 192 controls whose biopsy did not show epithelial proliferation, and 383 unbiopsied community controls matched to cases on age and area of residence. When cases were compared with community controls, there was little variation in the risk of BPED across levels of daily intake of energy, protein, and fat, but there was some suggestion of inverse associations with daily intake of retinol, beta-carotene, and fiber; in contrast, with biopsy controls as the comparison group, risk of BPED increased with increasing energy and fat intake but varied little with retinol, beta-carotene, and fiber intake. The results of this study provide additional evidence against roles for dietary energy and fat intake in the etiology of breast cancer. However, further studies of diet and BPED should be conducted in populations surveyed cross-sectionally for breast changes, in an attempt to limit or avoid the selection and misclassification biases to which studies of putative precursor lesions are susceptible.

Longitudinal association of measures of adiposity with serum antioxidant concentrations in postmenopausal women.

BACKGROUND/OBJECTIVES: The relationship between obesity and circulating levels of antioxidants is poorly understood. Most studies that have examined the association of adiposity with blood or tissue concentrations of antioxidant micronutrients have been cross-sectional, and few have compared the associations for indices of overall obesity and central obesity. Our aim was to prospectively examine the longitudinal association of body mass index (BMI), waist circumference (WC), waist circumference-height ratio (WCHtR) and waist-hip ratio (WHR) with major serum antioxidants in a population of postmenopausal women. SUBJECTS/METHODS: We used a subsample of participants in the Women's Health Initiative aged 50-79 years at entry with available fasting blood samples and anthropometric measurements obtained at multiple time points over 12.8 years of follow-up (N=2672). Blood samples were used to measure α-carotene, ß-carotene, ß-cryptoxanthin, lutein+zeaxanthin, α-tocopherol, γ-tocopherol and retinol at baseline, and at years 1, 3 and 6. We used mixed-effects linear regression analyses to examine associations between anthropometric measures and serum antioxidants at baseline and over time, controlling for covariates. RESULTS: In longitudinal analyses, carotenoids, and particularly ß-carotene, were strongly and inversely associated with BMI, WC and WCHtR and less so with WHR. α-Tocopherol showed a strong positive association with WHR but not with other anthropometric measures, whereas γ-tocopherol was positively and strongly associated with BMI, WC, WCHtR and less so with WHR. Retinol was positively associated with WHR. The inverse association of several carotenoids with anthropometric measures was stronger in never and former smokers compared with current smokers and in women without the metabolic syndrome. The inverse association of carotenoids with obesity measures may reflect reduced micronutrient concentrations owing to inflammation associated with obesity. CONCLUSIONS: In the present study, the strongest observed associations between anthropometric variables and micronutrients were an inverse association of WC with serum ß-carotene and a positive association of WC with γ-tocopherol.

Continuous Combined Estrogen Plus Progestin and Endometrial Cancer: The Women's Health Initiative Randomized Trial.

BACKGROUND: While progestin addition to estrogen mitigates endometrial cancer risk, the magnitude of the effect on incidence, specific endometrial cancer histologies, and endometrial cancer mortality remains unsettled. These issues were assessed by analyses after extended follow-up of the Women's Health Initiative (WHI) randomized clinical trial evaluating continuous combined estrogen plus progestin use. METHODS: The WHI enrolled 16 608 postmenopausal women into a randomly assigned, double-blind, placebo-controlled trial. Women age 50 to 79 years with intact uteri with normal endometrial biopsy at entry were randomly assigned to once-daily 0.625 mg conjugated equine estrogen plus 2.5mg medroxyprogesterone acetate (n = 8506) as a single pill or matching placebo (n = 8102). Follow-up beyond the original trial completion date required reconsent, obtained from 12 788 (83%) of surviving participants. Analyses were by intent-to-treat. All statistical tests were two-sided. RESULTS: After 5.6 years' median intervention and 13 years' median cumulative follow-up, there were fewer endometrial cancers in the combined hormone therapy compared with the placebo group (66 vs 95 case patients, yearly incidence, 0.06% vs 0.10%; hazard ratio [HR] = 0.65, 95% confidence interval [CI] = 0.48 to 0.89, P = .007). While there were somewhat fewer endometrial cancers during intervention (25 vs 30, respectively; HR = 0.77, 95% CI = 0.45 to 1.31), the difference became statistically significant postintervention (41 vs 65, respectively; HR = 0.59, 95% CI = 0.40 to 0.88, P = .008), but hazard ratios did not differ between phases (P difference = .46). There was a statistically nonsignificant reduction in deaths from endometrial cancer in the estrogen plus progestin group (5 vs 11 deaths, HR = 0.42, 95% CI = 0.15 to 1.22). CONCLUSION: In postmenopausal women, continuous combined estrogen plus progestin decreases endometrial cancer incidence.

Steroid hormone measurements from different types of assays in relation to body mass index and breast cancer risk in postmenopausal women: Reanalysis of eighteen prospective studies.

Epidemiological studies have examined breast cancer risk in relation to sex hormone concentrations measured by different methods: "extraction" immunoassays (with prior purification by organic solvent extraction, with or without column chromatography), "direct" immunoassays (no prior extraction or column chromatography), and more recently with mass spectrometry-based assays. We describe the associations of estradiol, estrone and testosterone with both body mass index and breast cancer risk in postmenopausal women according to assay method, using data from a collaborative pooled analysis of 18 prospective studies. In general, hormone concentrations were highest in studies that used direct assays and lowest in studies that used mass spectrometry-based assays. Estradiol and estrone were strongly positively associated with body mass index, regardless of the assay method; testosterone was positively associated with body mass index for direct assays, but less clearly for extraction assays, and there were few data for mass spectrometry assays. The correlations of estradiol with body mass index, estrone and testosterone were lower for direct assays than for extraction and mass spectrometry assays, suggesting that the estimates from the direct assays were less precise. For breast cancer risk, all three hormones were strongly positively associated with risk regardless of assay method (except for testosterone by mass spectrometry where there were few data), with no statistically significant differences in the trends, but differences may emerge as new data accumulate. Future epidemiological and clinical research studies should continue to use the most accurate assays that are feasible within the design characteristics of each study.

A cumulative case-control study of risk factor profiles for oncogenic and nononcogenic cervical human papillomavirus infections.

Human papillomaviruses (HPVs) play an essential role in the etiology of cervical cancer, but besides an established role for sexual transmission, little is known about other risk factors for HPV infection. Risk factors for nononcogenic, oncogenic, and HPV 16 cervical infections were investigated using a cumulative case-control approach nested in an ongoing cohort study of low income women from São Paulo, Brazil. HPV DNA was detected and typed by the MY09/11 PCR protocol. Risk factor information was obtained via interviews. In a case-control analysis, we compared women who harbored infections with exclusively nononcogenic types (n = 123), exclusively oncogenic types (n = 94), and any HPV 16 (n = 60) to women remaining HPV-negative (n = 512) throughout 1 year of follow-up. A strong negative association was found between age and oncogenic infections, but not with nononcogenic infections. Oral contraceptive use was strongly and exclusively associated with oncogenic and HPV 16 infections. Markers of sexual activity were associated with all types of infections, although with varying strengths. Our results suggest some important differences in the epidemiological correlates of HPV infection according to oncogenicity that may have implications for the-planning of specific preventive strategies aiming at reduction of cervical cancer risk.

Cigarette smoking and the risk of invasive epithelial ovarian cancer in a prospective cohort study.

Few cohort studies have examined the association between cigarette smoking and ovarian cancer risk, either overall, or by histological subtype. In relation to the latter, it has been suggested that mucinous ovarian tumours may be aetiologically unrelated to the other types of epithelial tumours and that their respective associations with cigarette smoking may differ. We examined the association between smoking and ovarian cancer risk using data from participants in a randomised controlled trial of screening for breast cancer involving 89,835 women aged 40-59 years at recruitment. Cox proportional hazards models were used to estimate rate ratios (RR) and 95% confidence intervals (CI). During an average of 16.5 years of follow-up, we observed 454 incident cases of ovarian cancer (184 serous, 67 endometrioid, 32 mucinous, 171 other or unknown). We found that women who had smoked for several decades had an approximately two-fold increased risk of epithelial ovarian cancer. Relative to never-smokers, women who had smoked for 40 years or more were at the highest risk (RR=2.50, 95% CI=1.37-4.56). The association with non-mucinous tumours was similar to that observed overall. For mucinous tumours, a two-fold increased risk was observed with smoking of shorter duration, although the number of mucinous tumours in our data-set was small. Long-term cigarette smoking may be associated with an increased risk of epithelial ovarian tumours.

Repeatability of interview-derived socio-demographic and medical information.

In this report, the repeatability of socio-demographic and medical information elicited by means of an interviewer-administered questionnaire is examined. One hundred and seven women who were controls in case-control studies of breast disease were re-interviewed approximately one year after initial interview. Both interviews addressed the same time period, namely that which preceded the first interview. For most of the quantitative variables studied, at least 70% of individuals provided two estimates (original and repeat) which were within one unit of each other. Also, comparison of the categorization of individuals on repeated measurements of qualitative variables (reports of events, operations and habits) revealed that most individuals were categorized consistently. This strong agreement between the original and repeat estimates was also reflected in the relatively high values of the summary measures of agreement (the intraclass correlation coefficient for quantitative variables and the Kappa statistic for qualitative variables) for most of the variables studied. The results of the present study on repeatability complement the results of previous research into the criterion validity of questionnaire-derived information and, taken together, suggest that information of relatively high quality may be obtained from such sources.