The Sister Study Cohort: Baseline Methods and Participant Characteristics.

BACKGROUND: The Sister Study was designed to address gaps in the study of environment and breast cancer by taking advantage of more frequent breast cancer diagnoses among women with a sister history of breast cancer and the presumed enrichment of shared environmental and genetic exposures. OBJECTIVE: The Sister Study sought a large cohort of women never diagnosed with breast cancer but who had a sister (full or half) diagnosed with breast cancer. METHODS: A multifaceted national effort employed novel strategies to recruit a diverse cohort, and collected biological and environmental samples and extensive data on potential breast cancer risk factors. RESULTS: The Sister Study enrolled 50,884 U.S. and Puerto Rican women 35-74y of age (median 56 y). Although the majority were non-Hispanic white, well educated, and economically well off, substantial numbers of harder-to-recruit women also enrolled (race/ethnicity other than non-Hispanic white: 16%; no college degree: 35%; household income <$50,000: 26%). Although all had a biologic sister with breast cancer, 16.5% had average or lower risk of breast cancer according to the Breast Cancer Risk Assessment Tool (Gail score). Most were postmenopausal (66%), parous with a first full-term pregnancy <30y of age (79%), never-smokers (56%) with body mass indexes (BMIs) of <29.9 kg/m2 (70%). Few (5%) reported any cancer prior to enrollment. CONCLUSIONS: The Sister Study is a unique cohort designed to efficiently study environmental and genetic risk factors for breast cancer. Extensive exposure data over the life-course and baseline specimens provide important opportunities for studying breast cancer and other health outcomes in women. Collaborations are welcome. https://doi.org/10.1289/EHP1923.

Changes in adherence to highly active antiretroviral therapy medications in the Multicenter AIDS Cohort Study.

OBJECTIVES: To characterize the determinants of changes in adherence to antiretroviral therapy and examine whether there are persistent lower adherers. DESIGN: A cohort study with repeated measurements. METHODS: Self-reported 100% adherence was defined as taking all doses and numbers of pills over a 4-day period as prescribed for current HIV medications. Independent predictors of changing adherence (< 100% to 100% and 100% to < 100%) were determined by logistic regression, correcting for correlated repeated measures for 597 HIV-positive men reporting the use of highly active antiretroviral therapy (HAART) between October 1998 and October 2000. RESULTS: Of the 942 visit-pairs with initial 100% adherence, 106 (11.3%) reduced adherence to less than 100%, and 836 (88.7%) remained 100% adherent at the next 6-month visit. No recent outpatient visits, younger age, depression, less than college educated, and later in calendar time predicted decreasing adherence. Among 186 visit-pairs starting with less than 100% adherence, 133 (71.5%) improved adherence to 100% and 53 (28.5%) remained less than 100% adherent at the next visit. The determinants of improving adherence included not being African-American, not using recreational drugs, and having had more than three HAART regimens. Lower adherence was not a random event; it was significantly correlated across visits within the individual. CONCLUSION: Characteristics associated with improving and lowering adherence differed and should be considered in developing interventions to enhance adherence and optimize effective therapies.

CC chemokine receptor 5 genotype and susceptibility to transmission of human immunodeficiency virus type 1 in women.

The human gene for CC chemokine receptor 5, a coreceptor for human immunodeficiency virus type 1 (HIV-1), affects susceptibility to infection. Most studies of predominantly male cohorts found that individuals carrying a homozygous deleted form of the gene, Delta 32, were protected against transmission, but protection did not extend to Delta 32 heterozygotes. The role played by this mutation in HIV-1 transmission to women was studied in 2605 participants in the Women's Interagency HIV Study. The Delta 32 gene frequency was 0.026 for HIV-1-seropositive women and 0.040 for HIV-1-seronegative women, and statistical analyses showed that Delta 32 heterozygotes were significantly less likely to be infected (odds ratio, 0.63 [95% confidence interval, 0.44-0.90]). The CCR5 Delta 32 heterozygous genotype may confer partial protection against HIV-1 infection in women. Because Delta 32 is rare in Africans and Asians, it seems plausible that differential genetic susceptibility, in addition to social and behavioral factors, may contribute to the rapid heterosexual spread of HIV-1 in Africa and Asia.