These data suggest that hyperinsulinemia is an independent risk factor for breast cancer and may have a substantial role in explaining the obesity-breast cancer relationship.

Obesity is a risk factor for colorectal cancer, and hyperinsulinemia, a common condition in obese patients, may underlie this relationship. Insulin, in addition to its metabolic effects, has promitotic and antiapoptotic activity that may be tumorigenic. Insulin-like growth factor (IGF)-I, a related hormone, shares sequence homology with insulin, and has even stronger mitogenic effects. However, few prospective colorectal cancer studies directly measured fasting insulin, and none evaluated free IGF-I, or endogenous estradiol, a potential cofactor in postmenopausal women. Therefore, we conducted a casecohort investigation of colorectal cancer among nondiabetic subjects enrolled in the Women's Health Initiative Observational Study, a prospective cohort of 93,676 postmenopausal women. Fasting baseline serum specimens from all incident colorectal cancer cases (n = 438) and a random subcohort (n = 816) of Women's Health Initiative Observational Study subjects were tested for insulin, glucose, total IGF-I, free IGF-I, IGF binding protein-3, and estradiol. Comparing extreme quartiles, insulin [hazard ratio (HR) q4-q1 , 1.73; 95% confidence interval (CI), 1.16-2.57; P trend = 0.005], waist circumference (HR q4-q1 , 1.82; 95% CI, 1.22-2.70; P trend = 0.001), and free IGF-I (HR q4-q1 , 1.35; 95% CI, 0.92-1.98; P trend = 0.05) were each associated with colorectal cancer incidence in multivariate models. However, these associations each became nonsignificant when adjusted for one another. Endogenous estradiol levels, in contrast, were positively associated with risk of colorectal cancer (HR comparing high versus low levels, 1.53; 95% CI, 1.05-2.22), even after control for insulin, free IGF-I, and waist circumference. These data suggest the existence of at least two independent biological pathways that are related to colorectal cancer: one that involves endogenous estradiol, and a second pathway broadly associated with obesity, hyperinsulinemia, and free IGF-I. [Cancer Res 2008;68(1):329-37]

Obesity is a major risk factor for endometrial cancer, a relationship thought to be largely explained by the prevalence of high estrogen levels in obese women. Obesity is also associated with high levels of insulin, a known mitogen. However, no prospective studies have directly assessed whether insulin and/or insulin-like growth factor-I (IGF-I), a related hormone, are associated with endometrial cancer while accounting for estrogen levels. We therefore conducted a case-cohort study of incident endometrial cancer in the Women's Health Initiative Observational Study, a prospective cohort of 93,676 postmenopausal women. The study involved all 250 incident cases and a random subcohort of 465 subjects for comparison. Insulin, total IGF-I, free IGF-I, IGF-binding protein-3, glucose, and estradiol levels were measured in fasting baseline serum specimens. Cox models were used to estimate associations with endometrial cancer, particularly endometrioid adenocarcinomas, the main histologic type (n = 205). Our data showed that insulin levels were positively associated with endometrioid adenocarcinoma [hazard ratio contrasting highest versus lowest quartile (HR q4-q1 ), 2.33; 95% confidence interval (95% CI), 1.13-4.82] among women not using hormone therapy after adjustment for age and estradiol. Free IGF-I was inversely associated with endometrioid adenocarcinoma (HR q4-q1 , 0.53; 95% CI, 0.31-0.90) after adjustment for age, hormone therapy use, and estradiol. Both of these associations were stronger among overweight/obese women, especially the association between insulin and endometrioid adenocarcinoma (HR q4-q1 , 4.30; 95% CI, 1.62-11.43). These data indicate that hyperinsulinemia may represent a risk factor for endometrioid adenocarcinoma that is independent of estradiol. Free IGF-I levels were inversely associated with endometrioid adenocarcinoma, consistent with prior cross-sectional data. (Cancer Epidemiol Biomarkers Prev 2008;17(4):921 -9)

ERVICAL CANCER SCREENING recommendations in the United States have been recently updated and now advise using an interval of 3 years between screenings in healthy women 30 years or older who have normal cytology results and who test negative for oncogenic (cancer-associated) human papillomavirus (HPV) DNA. 1,2 The recommended interval is 6 to 12 months for women with normal cytology results and detectable oncogenic HPV. If no HPV test is conducted, 3 consecutive normal annual Papanicolaou (Pap) smear results are required before the Pap smear frequency is changed to once every 2 or 3 years. Support for these recommendations comes from several large observational studies. 1-5 However, guidelines for human immunodeficiency virus (HIV)-seropositive women have not been revised since Context Recent cervical cancer screening guidelines state that the interval between screenings can be safely extended to 3 years in healthy women 30 years or older who have normal cytology results and have negative test results for oncogenic human papillomavirus (HPV) DNA. Objective To determine the incidence of squamous intraepithelial lesions (SILs) in HIV-seropositive women with normal cytology results, by baseline HPV DNA results. Design, Setting, and Patients Participants were HIV-seropositive (n=855; mean age, 36 years) and HIV-seronegative (n=343; mean age, 34 years) US women with normal baseline cervical cytology who were enrolled in the Women's Interagency HIV Study (WIHS), a large, multi-institutional prospective cohort study. Since their recruitment during 1994-1995, WIHS participants have been followed up semi-annually with repeated Pap smears for a median of 7 years. Main Outcome Measure The cumulative incidence of any SIL and high-grade SIL or cancer (HSILϩ) was estimated according to baseline HPV DNA results, stratified by HIV serostatus and CD4 T-cell count. Results Development of any SIL in women with negative HPV results (both oncogenic and nononcogenic) at 2 years was as follows: in HIV-seropositive women with CD4 counts less than 200/µL, 9% (95% CI, 1%-18%); with CD4 counts between 200/µL and 500/µL, 9% (95% CI, 4%-13%); and with CD4 counts greater than 500/ µL, 4% (95% CI, 1%-7%). The CIs for these estimates overlapped with those for HIVseronegative women with normal baseline cytology who were HPV-negative (3%; 95% CI, 1%-5%), indicating that at 2 years, there were no large absolute differences in the cumulative incidence of any SIL between groups. Furthermore, no HPV-negative participants in any group developed HSILϩ lesions within 3 years. Multivariate Cox models showed that on a relative scale, the incidence of any SIL among HIVseropositive women with CD4 counts greater than 500/µL (hazard ratio [HR], 1.2; 95% CI, 0.5-3.0), but not those with CD4 counts less than or equal to 500/µL (HR, 2.9; 95% CI, 1.2-7.1), was similar to that in HIV-seronegative women. Conclusion The similar low cumulative incidence of any SIL among HIVseronegative and HIV-seropositive women with CD4 counts greater than 500/µL and who had normal ...

M ore than 4 million women and men in the United States and 150 million people worldwide are estimated to be hepatitis C virus (HCV) seropositive. 1,2 Most of these individuals are chronically infected with the virus and are at high risk of cirrhosis, hepatocellular carcinoma, and liverrelated death. The natural history of HCV infection, however, is highly variable. Some individuals do not become HCV infected despite high levels of exposure. 3 Other individuals may clear HCV RNA following acute infection, and whereas some individuals with long-term HCV viremia remain clinically asymptomatic, others have progressive disease. 4 Indeed, marked variability in natural history is seen even among groups of individuals with single-source exposure to HCV, as occurred in a population of Irish women exposed to HCV-contaminated anti-D immune globulin. 5 Together these observations suggest that host factors, particularly host immune response, play a key role in the regulation of HCV pathogenesis.

Purpose To evaluate whether a change in fitness is associated with academic outcomes in New York City (NYC) middle school students using longitudinal data, and to evaluate whether this relationship is modified by student household poverty. Methods This was a longitudinal study of 83,111 NYC middle school students enrolled between 2006–07 and 2011–12. Fitness was measured as a composite percentile based on three fitness tests and categorized based on change from the previous year. The effect of the fitness change level on academic outcomes, measured as a composite percentile based on state standardized mathematics and English Language Arts test scores, was estimated using a multilevel growth model. Models were stratified by sex and additional models were tested stratified by student household poverty. Results For both girls and boys, a substantial increase in fitness from the previous year resulted in a greater improvement in academic ranking than was seen in the reference group (girls: .36 greater percentile point improvement, 95% confidence interval: .09-.63; boys: .38 greater percentile point improvement, 95% confidence interval: .09-.66). A substantial decrease in fitness was associated with a decrease in academics in both boys and girls. Effects of fitness on academics were stronger in high-poverty boys and girls than in low-poverty boys and girls. Conclusions Academic rankings improved for boys and girls who increased their fitness level by >20 percentile points relative to other students. Opportunities for increased physical fitness may be important to support academic performance.

Treatment failure and recurrence are common in women with HIV but are usually low grade.

IntroductionAlthough studies have shown that childhood obesity overall is on the decline among New York City (NYC) public school children, the prevalence of severe childhood obesity has not been studied.MethodsWe used height and weight measurements of 947,765 NYC public school students aged 5 to 14 years in kindergarten through 8th grade (K–8), from school years 2006–07 through 2010–11. We used age- and sex-specific body mass index (BMI) percentiles according to Centers for Disease Control and Prevention growth charts to define childhood obesity (BMI ≥ 95th percentile) and severe childhood obesity (BMI ≥120% of 95th percentile) and to identify biologically implausible values (BIV). Multivariable logistic models tested for trends in obesity and severe obesity prevalence. To evaluate misclassification, we recalculated prevalence estimates for the most recent school year (2010–11) including the student records identified as BIV who were also declared severely obese (BMI ≥ 120% of 95th percentile). We refer to this subgroup of BIVs as “high BIV.”ResultsSevere obesity among NYC public school students in grades K–8 decreased 9.5% from the 2006–07 school year (6.3%) to the 2010–11 school year (5.7%), and obesity decreased 5.5% (from 21.9% to 20.7%). The prevalence of severe obesity and obesity was highest among minority, poor, and male children. Severe obesity declined in prevalence among every subgroup, with the greatest effect among white students and wealthy students. Severe obesity prevalence increased with age, and obesity prevalence peaked among those aged 7 to 10 years. For the 2010–11 school year, including high BIVs increased severe obesity prevalence from 5.7% to 6.6% and increased obesity prevalence from 20.7% to 21.5%.ConclusionAmong all subgroups of NYC public school children in grades K–8, the reduction in severe obesity was greater than the reduction in overall obesity. Efforts to decrease obesity in NYC have affected the severely obese; however, monitoring of this specific subgroup should continue because of differences in trends and greater health risks.