Ugonna Ihenacho

Genetic risk factors for orofacial clefts in Central Africans and Southeast Asians

Genome‐wide association studies (GWAS) for orofacial clefts have identified several susceptibility regions, but have largely focused on non‐Hispanic White populations in developed countries. We performed a targeted genome‐wide study of single nucleotide polymorphisms (SNPs) in exons using the Illumina HumanExome+ array with custom fine mapping of 16 cleft susceptibility regions in three underserved populations: Congolese (87 case‐mother, 210 control‐mother pairs), Vietnamese (131 case‐parent trios), and Filipinos (42 case‐mother, 99 control‐mother pairs). All cases were children with cleft lip with or without cleft palate. Families were recruited from local hospitals and parental exposures were collected using interviewer‐administered questionnaires. We used logistic regression models for case‐control analyses, family‐based association tests for trios, and fixed‐effect meta‐analyses to determine individual SNP effects corrected for multiple testing. Of the 16 known susceptibility regions tested, SNPs in four regions reached statistical significance in one or more of these populations: 1q32.2 (IRF6), 10q25.3 (VAX1), and 17q22 (NOG). Due to different linkage disequilibrium patterns, significant SNPs in these regions differed between the Vietnamese and Filipino populations from the index SNP selected from previous GWAS studies. Among Africans, there were no significant associations identified for any of the susceptibility regions. rs10787738 near VAX1 (Pu2009=u20094.98E−3) and rs7987165 (Pu2009=u20096.1E−6) were significant in the meta‐analysis of all three populations combined. These results confirm several known susceptibility regions and identify novel risk alleles in understudied populations.

Genome-wide Association Study of Colorectal Cancer in Hispanics

Summary This manuscript describes the first large-scale genome-wide association study of colorectal cancer in Hispanics and Latinos. Our results demonstrate the broad replication of known susceptibility regions and the importance of fine-mapping in ethnic minority populations.

Parental risk factors for oral clefts among Central Africans, Southeast Asians, and Central Americans

Background Several lifestyle and environmental exposures have been suspected as risk factors for oral clefts, although few have been convincingly demonstrated. Studies across global diverse populations could offer additional insight given varying types and levels of exposures. Methods We performed an international case–control study in the Democratic Republic of the Congo (133 cases, 301 controls), Vietnam (75 cases, 158 controls), the Philippines (102 cases, 152 controls), and Honduras (120 cases, 143 controls). Mothers were recruited from hospitals and their exposures were collected from interviewer‐administered questionnaires. We used logistic regression modeling to estimate odds ratios (OR) and 95% confidence intervals (CI). Results Family history of clefts was strongly associated with increased risk (maternal: OR = 4.7; 95% CI, 3.0–7.2; paternal: OR = 10.5; 95% CI, 5.9–18.8; siblings: OR = 5.3; 95% CI, 1.4–19.9). Advanced maternal age (5 year OR = 1.2; 95% CI, 1.0–1.3), pregestational hypertension (OR = 2.6; 95% CI, 1.3–5.1), and gestational seizures (OR = 2.9; 95% CI, 1.1–7.4) were statistically significant risk factors. Lower maternal (secondary school OR = 1.6; 95% CI, 1.2–2.2; primary school OR = 2.4, 95% CI, 1.6–2.8) and paternal education (OR = 1.9; 95% CI, 1.4–2.5; and OR = 1.8; 95% CI, 1.1–2.9, respectively) and paternal tobacco smoking (OR = 1.5, 95% CI, 1.1–1.9) were associated with an increased risk. No other significant associations between maternal and paternal factors were found; some environmental factors including rural residency, indoor cooking with wood, chemicals and water source appeared to be associated with an increased risk in adjusted models. Conclusion Our study represents one of the first international studies investigating risk factors for clefts among multiethnic underserved populations. Our findings suggest a multifactorial etiology including both maternal and paternal factors. Birth Defects Research (Part A) 103:863–879, 2015.

Genetic variation in insulin pathway genes and distal colorectal adenoma risk.

BackgroundInsulin, glucose, and other insulin-related proteins that mediate insulin signaling are associated with colorectal neoplasia risk, but associations with common genetic variation in insulin axis genes are less clear. In this study, we used a comprehensive tag single-nucleotide polymorphisms (SNPs) approach to define genetic variation in six insulin axis genes (IGF1, IGF2, IGFBP1, IGFBP3, IRS1, and IRS2) and three genes associated with estrogen signaling (ESR1, ESR2, and PGR).MethodsWe assessed associations between SNPs and distal colorectal adenoma (CRA) risk in a case–control study of 1,351 subjects. Cases were individuals with one or more adenomas diagnosed during sigmoidoscopy, and controls were individuals with no adenomas at the sigmoidoscopy exam. We used unconditional logistic regression assuming an additive model to assess SNP-specific risks adjusting for multiple comparisons with Pact.ResultsDistal adenoma risk was significantly increased for one SNP in IGF2 [per minor allele ORu2009=u20091.41; 95xa0% confidence interval (CI)u2009=u20091.16, 1.67; Pactu2009=u20090.005] and decreased for an ESR2 SNP (per minor allele ORu2009=u20090.78; 95xa0% CIu2009=u20090.66, 0.91; Pactu2009=u20090.041). There was no statistically significant heterogeneity of these associations by race, sex, BMI, physical activity, or, in women, hormone replacement therapy use. Risk estimates did not differ in the colon versus rectum or for smaller (<1xa0cm) versus larger (>1xa0cm) adenomas.ConclusionsThese data suggest that selected genetic variability in IGF2 and ESR2 may be modifiers of CRA risk.

Shared health characteristics in Hispanic colorectal cancer patients and their primary social support person following primary diagnosis

The aim of this paper was to determine individual and shared levels of psychosocial, behavioral, and symptomological health characteristics among Hispanics with recent history of cancer and their primary social support person (PSSP) in the years following diagnosis.

Availability of long-acting reversible contraceptives in Los Angeles County clinics through a Medicaid state plan amendment program

OBJECTIVEnTo assess the availability of long acting reversible contraceptive (LARC) methods in Los Angeles County through providers participating in a California State Medicaid State Plan Amendment Program called Family Planning, Access, Care and Treatment (Family PACT).nnnSTUDY DESIGNnThis was a cross-sectional telephone survey utilizing secret shopper methodology. From 855 Family PACT providers in Los Angeles County in 2015, a representative sample of 400 providers was selected for study. Young female researchers posing as potential patients called each sampled clinic to ask a scripted series of questions about LARC availability for Family PACT patients in that practice.nnnRESULTSnAll but one eligible practice (99.7%) responded to our questions. Among the 336 responding practices, 284 said they accepted Family PACT. Of those accepting Family PACT, staff answering the telephone call at 61% said they did not provide any LARC method onsite, 2% provided all currently available LARC methods, and 6% provided same-day placement of any LARC.nnnCONCLUSIONnThe majority of Family PACT practices surveyed said that they did not provide any LARC onsite, and very few provided same-day LARC placement despite easy patient enrollment procedures, relatively reasonable reimbursement and concerted efforts to increase LARC use. Substantial barriers to greater uptake may rest at the provider level with either actual unavailability of LARC or staff perception of unavailability.nnnIMPLICATIONSnOnly a minority of Family PACT practices said that LARC methods were available onsite, which imposes substantial restriction to access for women who are entitled to have access without cost. Other states developing programs should be aware of this challenge.

Paternal Risk Factors for Oral Clefts in Northern Africans, Southeast Asians, and Central Americans

While several studies have investigated maternal exposures as risk factors for oral clefts, few have examined paternal factors. We conducted an international multi-centered case–control study to better understand paternal risk exposures for oral clefts (cases = 392 and controls = 234). Participants were recruited from local hospitals and oral cleft repair surgical missions in Vietnam, the Philippines, Honduras, and Morocco. Questionnaires were administered to fathers and mothers separately to elicit risk factor and family history data. Associations between paternal exposures and risk of clefts were assessed using logistic regression adjusting for potential confounders. A father’s personal/family history of clefts was associated with significantly increased risk (adjusted OR: 4.77; 95% CI: 2.41–9.45). No other significant associations were identified for other suspected risk factors, including education (none/primary school v. university adjusted OR: 1.29; 95% CI: 0.74–2.24), advanced paternal age (5-year adjusted OR: 0.98; 95% CI: 0.84–1.16), or pre-pregnancy tobacco use (adjusted OR: 0.96; 95% CI: 0.67–1.37). Although sample size was limited, significantly decreased risks were observed for fathers with selected occupations. Further research is needed to investigate paternal environmental exposures as cleft risk factors.