Association of Life-Course Educational Attainment and Breast Cancer Grade in the MEND Study.

Background: Nigeria reports the highest age-standardized mortality rate for breast cancer (BC) among African countries and disproportionately high rates of high-grade cancer. Histological grade is a strong predictor of mortality, and evidence suggests that educational attainment influences cancer outcomes. Objective: We characterize the association between educational trends across the life-course and BC grade at diagnosis. Methods: Data on 224 BC patients enrolled in the Mechanisms for Established and Novel Risk Factors for Breast Cancer in Nigerian Women (MEND) study was analyzed. Participant and parental (mother and father) education was categorized as low (primary school or less) or high (secondary school or greater). Accordingly, the educational trend across the life-course was determined for each participant relative to each parent: stable high, increasing, decreasing, or stable low. BC grade was classified as high (grade 3) or low (grades 1-2). Findings: About 34% of participants, 71% of fathers, and 85% of mothers had low education. Approximately one-third of participants were diagnosed with high-grade BC. Participants with low-grade BC were more likely to have highly educated fathers (p = 0.04). After adjusting for age, comorbidities, marital status and mammogram screening, participants with highly educated fathers were 60% less likely to have high-grade BC (aOR 0.41; 95% CI 0.20 to 0.84) compared to those with less-educated fathers. Stable high life-course education relative to father was also associated with a significantly lower likelihood of having high-grade BC (aOR 0.36; 95% CI 0.15 to 0.87) compared to stable low life-course education. No significant associations were observed for the participant's education, mother's education, or life-course education relative to mother. Conclusions: Early-life socioeconomic status (SES) may influence BC grade. This deserves further study to inform policies that may be useful in reducing high-grade BC in Nigeria.

Could epigenetics help explain racial disparities in chronic pain?

African Americans disproportionately suffer more severe and debilitating morbidity from chronic pain than do non-Hispanic Whites. These differences may arise from differential exposure to psychosocial and environmental factors such as adverse childhood experiences, racial discrimination, low socioeconomic status, and depression, all of which have been associated with chronic stress and chronic pain. Race, as a social construct, makes it such that African Americans are more likely to experience different early life conditions, which may induce epigenetic changes that sustain racial differences in chronic pain. Epigenetics is one mechanism by which environmental factors such as childhood stress, racial discrimination, economic hardship, and depression can affect gene expression without altering the underlying genetic sequence. This article provides a narrative review of the literature on epigenetics as a mechanism by which differential environmental exposure could explain racial differences in chronic pain. Most studies of epigenetic changes in chronic pain examine DNA methylation. DNA methylation is altered in the glucocorticoid (stress response) receptor gene, NR3C1, which has been associated with depression, childhood stress, low socioeconomic status, and chronic pain. Similarly, DNA methylation patterns of immune cytokine genes have been associated with chronic stress states. Thus, DNA methylation changes may play an essential role in the epigenetic modulation of chronic pain in different races with a higher incidence of epigenetic alterations contributing to more severe and disabling chronic pain in African Americans.

Assessment of telomere length and factors that contribute to its stability.

Short strands of tandem hexameric repeats known as telomeres cap the ends of linear chromosomes. These repeats protect chromosomes from degradation and prevent chromosomal end-joining, a phenomenon that could occur due to the end-replication problem. Telomeres are maintained by the activity of the enzyme telomerase. The total number of telomeric repeats at the terminal end of a chromosome determines the telomere length, which in addition to its importance in chromosomal stabilization is a useful indicator of telomerase activity in normal and malignant tissues. Telomere length stability is one of the important factors that contribute to the proliferative capacity of many cancer cell types; therefore, the detection and estimation of telomere length is extremely important. Until relatively recently, telomere lengths were analyzed primarily using the standard Southern blot technique. However, the complexities of this technique have led to the search for more simple and rapid detection methods. Improvements such as the use of fluorescent probes and the ability to sort cells have greatly enhanced the ease and sensitivity of telomere length measurements. Recent advances, and the limitations of these techniques are evaluated. Drugs that assist in telomere shortening may contribute to tumor regression. Therefore, factors that contribute to telomere stability may influence the efficiency of the drugs that have potential in cancer therapy. These factors in relation to telomere length are also examined in this analysis.