Lung Cancer in Ever- and Never-Smokers: Findings from Multi-Population GWAS Studies.

Background: Clinical, molecular, and genetic epidemiology studies displayed remarkable differences between ever- and never-smoking lung cancer.

Methods: We conducted a stratified multi-population (European, East Asian, and African descent) association study on 44,823 ever-smokers and 20,074 never-smokers to identify novel variants that were missed in the non-stratified analysis. Functional analysis including expression quantitative trait loci (eQTL) colocalization and DNA damage assays, and annotation studies were conducted to evaluate the functional roles of the variants.

Exposure to Perfluoroalkyl Substances and Associations with Pubertal Onset and Serum Reproductive Hormones in a Longitudinal Study of Young Girls in Greater Cincinnati and the San Francisco Bay Area.

Background: Per- and polyfluoroalkyl substances (PFAS), endocrine disrupting chemicals with worldwide exposure, cause changes in mammary gland development in rodents. A few human studies report delay in pubertal events with increasing perfluorooctanoic acid (PFOA) exposure, but to our knowledge none have examined reproductive hormone levels at thelarche.

Methods: In a cohort of Greater Cincinnati (GC) and San Francisco Bay Area (SFBA) girls recruited at 6-8 years of age, clinical examinations were conducted annually or semiannually with sequential Tanner staging.

Migraine and its association with pubertal maturation and behavioral traits among adolescent girls.

Objective: To determine if the ages at pubertal milestones are associated with the prevalence of adolescent migraine.

Background: Migraine headaches are a common disease in adolescent girls. Past studies have evaluated the relationship between age of onset of menarche and migraine headache, but none have studied earlier pubertal milestones such as thelarche and pubarche.

CRAG: de novo characterization of cell-free DNA fragmentation hotspots in plasma whole-genome sequencing.

The fine-scale cell-free DNA fragmentation patterns in early-stage cancers are poorly understood. We developed a de novo approach to characterize the cell-free DNA fragmentation hotspots from plasma whole-genome sequencing. Hotspots are enriched in open chromatin regions, and, interestingly, 3'end of transposons.

Exposure to neonicotinoids and serum testosterone in men, women, and children.

Neonicotinoids are the most used pesticides in the world and, despite being harmful to honeybees, they are considered safe for mammals. However, they have been associated with decreasing testosterone levels in several experimental animal models. In the present study, we aimed to determine the association of urinary neonicotinoids with serum testosterone in humans.

Genome-wide interaction analysis identified low-frequency variants with sex disparity in lung cancer risk.

Differences by sex in lung cancer incidence and mortality have been reported which cannot be fully explained by sex differences in smoking behavior, implying existence of genetic and molecular basis for sex disparity in lung cancer development. However, the information about sex dimorphism in lung cancer risk is quite limited despite the great success in lung cancer association studies. By adopting a stringent two-stage analysis strategy, we performed a genome-wide gene-sex interaction analysis using genotypes from a lung cancer cohort including ~ 47 000 individuals with European ancestry.

The Impact of Macronutrient Intake on Sex Steroids During Onset of Puberty.

Introduction: Increased fiber intake has been associated with decreased breast cancer risk, while increased animal protein intake with increased risk. The objective of this study is to examine the relationship of dietary fiber and protein intake to estrogen and sex hormone-binding globulin (SHBG) concentrations at puberty onset.

Methods: These analyses were conducted using the Cincinnati puberty cohort of the Breast Cancer and the Environment Research Program, with girls followed every 6 months from ages 6 and 7.

Air pollution and the pandemic: Long-term PM exposure and disease severity in COVID-19 patients.

Background And Objective: Ecological studies have suggested an association between exposure to particulate matter ≤2.5 μm (PM ) and coronavirus disease 2019 (COVID-19) severity. However, these findings are yet to be validated in individual-level studies.

The Association between Sex Hormones, Pubertal Milestones and Benzophenone-3 Exposure, Measured by Urinary Biomarker or Questionnaire.

Experimental studies have suggested benzophenone-3 (BP-3), a sunscreen ingredient, may have endocrine-disrupting properties. A cohort of girls were recruited at ages 6-7 years and returned semi-annually for pubertal maturation staging, provided blood for serum hormone analyses [estradiol, estrone, testosterone, dehydroepiandrosterone-sulfate (DHEA-S)], and urine to measure BP-3 concentrations. We found a significant negative linear association between amount of reported sunscreen use and testosterone levels at the onset of puberty (N = 157, adjusted β = -0.

Childhood Socioeconomic Status and Menarche: A Prospective Study.

Purpose: The relationship between socioeconomic status (SES) and menarche has implications for understanding social level influences on early life development and adult disease, including breast cancer, but remains ill defined. We report here results from the Breast Cancer and the Environment Research Program, which permitted a longitudinal study of age at menarche in relationship to childhood SES in a diverse cohort of 1,069 girls across three urban areas of the United States.

Methods: We assessed the association of SES index quintiles with age at pubertal onset with breast budding and subsequent tempo to the age at menarche between 2004 and 2015 using multiple-event Cox regression models to estimate hazard ratios and 95% confidence intervals.

Genetic Variation and Recurrent Haplotypes on Chromosome 6q23-25 Risk Locus in Familial Lung Cancer.

Although lung cancer is known to be caused by environmental factors, it has also been shown to have genetic components, and the genetic etiology of lung cancer remains understudied. We previously identified a lung cancer risk locus on 6q23-25 using microsatellite data in families with a history of lung cancer. To further elucidate that signal, we performed targeted sequencing on nine of our most strongly linked families.

Authentic Youth Engagement in Environmental Health Research and Advocacy.

Training in environmental health (EH) engages and inspires youth to tackle health promotion and policy change. Yet, there is little guidance on how to successfully nurture and sustain youth engagement. This paper compares four case studies of youth engagement to promote EH in rural and urban communities using the Youth Empowerment Solutions (YES!) framework.

Girls' Pubertal Timing and Tempo and Mental Health: A Longitudinal Examination in an Ethnically Diverse Sample.

Purpose: Earlier timing and faster tempo of puberty have been linked to adolescents' poor mental health. Previous research rarely adjusted for childhood mental health, did not use physical examination to assess puberty, and excluded Latinas and Asian Americans. This study addressed these limitations.

Rare deleterious germline variants and risk of lung cancer.

Recent studies suggest that rare variants exhibit stronger effect sizes and might play a crucial role in the etiology of lung cancers (LC). Whole exome plus targeted sequencing of germline DNA was performed on 1045 LC cases and 885 controls in the discovery set. To unveil the inherited causal variants, we focused on rare and predicted deleterious variants and small indels enriched in cases or controls.

Long-term exposure to fine particulate matter and hospitalization in COVID-19 patients.

Background: Ecological evidence suggests that exposure to air pollution affects coronavirus disease 2019 (COVID-19) outcomes. However, no individual-level study has confirmed the association to date.

Methods: We identified COVID-19 patients diagnosed at the University of Cincinnati hospitals and clinics and estimated particulate matter ≤2.

High School Students as Citizen Scientists to Decrease Radon Exposure.

Residents in rural Kentucky (KY) and suburban Ohio (OH) expressed concerns about radon exposure and lung cancer. Although 85% of lung cancer cases are caused by tobacco smoke, radon exposure accounts for 10-15% of lung cancer cases. Academic and community members from the University of KY and the University of Cincinnati developed and pilot-tested a family-centered, youth-engaged home radon testing toolkit.

Pubertal Growth, IGF-1, and Windows of Susceptibility: Puberty and Future Breast Cancer Risk.

Purpose: Risk markers for breast cancer include earlier onset of menarche (age at menarche [AAM]) and peak height velocity (PHV). Insulin-like growth factor-1 (IGF-1) is associated with pubertal milestones, as well as cancer risk. This study examined the relationships between pubertal milestones associated with breast cancer risk and hormone changes in puberty.

Onset of Puberty: Mother Knows Best.

Study Objective: Several strategies have been proposed to determine onset of puberty without examination by a trained professional. This study sought to evaluate a novel approach to determine onset of puberty in girls.

Design, Setting, And Participants: This study used the Cincinnati cohort of the Breast Cancer and the Environment Research Program.

Whole Exome Sequencing of Highly Aggregated Lung Cancer Families Reveals Linked Loci for Increased Cancer Risk on Chromosomes 12q, 7p, and 4q.

Background: Lung cancer kills more people than any other cancer in the United States. In addition to environmental factors, lung cancer has genetic risk factors as well, though the genetic etiology is still not well understood. We have performed whole exome sequencing on 262 individuals from 28 extended families with a family history of lung cancer.

Sex Hormone Phenotypes in Young Girls and the Age at Pubertal Milestones.

Context: The age of pubertal onset is influenced by many variables in young girls. Previous studies have not examined sex hormones longitudinally around the time of breast development and their relationship to pubertal onset.

Objective: We sought to use an unbiased statistical approach to identify phenotypes of sex hormones in young girls and examine their relationship with pubertal milestones.

Longitudinal study of age of menarche in association with childhood concentrations of persistent organic pollutants.

Background: Age at female puberty is associated with adult morbidities, including breast cancer and diabetes. Hormonally active chemicals are suspected of altering pubertal timing. We examined whether persistent organic pollutants (POPs) are associated with age at menarche in a longitudinal study.

Complex relationships between perfluorooctanoate, body mass index, insulin resistance and serum lipids in young girls.

Background: Perfluorooctanoate (PFOA) has been used extensively in the manufacture of both commercial and household products. PFOA serum concentrations have been associated with adverse health effects, including lower body mass in children and infants.

Objective: To determine if there is an association between serum PFOA concentration and body mass, serum insulin and lipid profile in exposed young girls.

Untangling the ethical intersection of epidemiology, human subjects research, and public health.

Purpose: Members of the American College of Epidemiology (ACE) Ethics Committee identified current ethics and epidemiology topic areas to consider for further discussion, consultation, teaching opportunities, and conference presentation. This article reflects on the activities of the Committee at the ACE Annual Meeting in New Orleans, Louisiana, September 24-26, 2017.

Methods: The overall aim for the Ethics Committee was to engage members of the College and other audiences and highlight the evolution of ethics and epidemiology since the inception of the original Ethics Guidelines published by the ACE Ethics and Standards of Practice Committee in 2000.