Public health plays an important role in ensuring access to interventions that can prevent disease, including the implementation of evidence-based genomic recommendations. We used the Centers for Disease Control and Prevention (CDC) Science Impact Framework to trace the impact of public health activities and partnerships on the implementation of the 2009 Evaluation of Genomic Applications in Practice and Prevention (EGAPP) Lynch Syndrome screening recommendation and the 2005 and 2013 United States Preventive Services Task Force (USPSTF) BRCA1 and BRCA2 testing recommendations.The EGAPP and USPSTF recommendations have each been cited by >300 peer-reviewed publications. CDC funds selected states to build capacity to integrate these recommendations into public health programs, through education, policy, surveillance, and partnerships. Most state cancer control plans include genomics-related goals, objectives, or strategies. Since the EGAPP recommendation, major public and private payers now provide coverage for Lynch Syndrome screening for all newly diagnosed colorectal cancers. National guidelines and initiatives, including Healthy People 2020, included similar recommendations and cited the EGAPP and USPSTF recommendations. However, disparities in implementation based on race, ethnicity, and rural residence remain challenges. Public health achievements in promoting the evidence-based use of genomics for the prevention of hereditary cancers can inform future applications of genomics in public health.

Prevention and early detection is critical for reducing the population cancer burden. Two approaches have been used: Population approaches change social norms (e.g., smoking bans) or impose incentives (e.g., cigarette taxes); high-risk strategies intervene upon individuals with elevated cancer risk (e.g., smoking cessation). Knowledge about carcinogenesis mechanisms, extreme exposures, and inherited susceptibility provides opportunities to develop precision prevention and early-detection (PPED) strategies. PPED aims to understand the basis of risk, identify groups that optimally benefit from interventions, characterize heterogeneity in intervention responses, optimize intervention timing, and minimize toxicities. We propose a framework around which PPED strategies can be developed. Currently available cancer prevention and early-detection approaches have the potential to reduce a large proportion of the cancer burden in the population. However, even if fully implemented, existing methods cannot fully eliminate the cancer burden. New PPED approaches that exploit the growing knowledge of molecular and biological cancer mechanisms should be developed and implemented. Cancer Discov; 8(7); 1-9. ©2018 AACR.

p53 is a powerful transcription factor playing a pivotal role in the prevention of cancer development and in maintaining genome integrity. This oncosuppressor is found to be functionally inactivated by mutations in many human tumors. Accordingly, wild type p53 and its oncogenic mutants represent valuable cancer biomarkers for diagnostic and prognostic purposes. We developed a highly sensitive biosensor, based on Surface Enhanced Raman Spectroscopy, for detection of wild type p53 and of p53R175H, which is one of the most frequent tumor-associated mutants of p53. Our approach combines the huge Raman signal enhancement, mainly arising from the plasmonic resonance effect on molecules close to gold nanoparticles, with the antigen-antibody biorecognition specificity. By following the enhanced signal of a specific Raman marker, intrinsic to the nanoparticle-antibody bioconjugation, we were able to push the antigen detection level down to the attomolar range in buffer and to the femtomolar range in spiked human serum. The method demonstrated a high reproducibility and a remarkable selectivity in discriminating between wild type p53 and p53R175H mutant, in both buffer and serum. A calibration plot was built and validated by ELISA for a reliable quantification of p53. These findings entitle our SERS-based immunosensor as a powerful and reliable tool for a non-invasive screening in human serum targeting p53 network. The approach could be easily extended to ultrasensitive detection of other markers of general interest, with feasible implementations into multiplex assays, functioning as lab-on-chip devices for several applications.

Barrett's esophagus (BE) is a very common condition. We have obtained fairly profound knowledge of the natural history of this condition. This results from many cross-sectional and cohort studies, many describing patients undergoing long-term surveillance. Their consent to use their clinical data has improved our knowledge to the benefit of these same and other patients. The prevalence of BE increases with age both in men and in women. This increase starts at a younger age in men than in women. The incidence of high-grade dysplasia and cancer in BE depends on segment length, gender, and age. The latter two likely indicate the duration of the presence of BE in an individual patient. Other factors that influence the incidence of dysplasia and cancer are smoking behavior and use of certain medications such as PPIs, statins, and NSAIDs. Surveillance of BE and treatment of dysplasia can impact the incidence of and mortality due to esophageal adenocarcinoma. This is of major benefit to a subgroup of BE patients. The epidemiology and burden of disease ask for further efforts to develop targeted screening, surveillance, and intervention techniques in coming years.

There is a great variation in the prevalence of cervical HPV infection worldwide with some of the highest rates being found in African women. Early onset of sexual activity (≤ 15 age), multiparity and sexual promiscuity have been recognized as some of the significant risk factors for HPV infection. In Nigeria, there is scarcity of data on the degree of relationship between these factors and the prevalence of HPV infection. Thus, this study was designed to determine the prevalence of genital HPV infection with its potential risk factors among women in Southwest Nigeria. Cervical swab specimen was collected from 295 consenting women including those presenting for routine cervical cancer screening, STI clinic attendees and women who attended community based outreach programmes. Viral DNA was extracted from the swab samples using commercially available DNA extraction Kit and amplified by PCR using two set of consensus primers (PGMY09/11 and degenerate GP-E6/E7). Fifty-five samples were positive to HPV DNA giving a prevalence of 18.6%. Risk factors such as lack of formal education (P-value: 0.003), divorcee (P-value: 0.019), polygamy (P-value: 0.027), unemployment (P-value: 0.023), low income earnings (P-value: 0.018), younger age (<18years) at sexual debut (P-value: 0.039) and passive smoking (P-value: 0.017) were significantly associated with HPV infection. High HPV prevalence and associated risk factors observed in this study shows the continuous transmission of the virus in Southwest Nigeria. Hence, enlarged monitoring including intense public awareness and cervical cancer screening is urgently needed for prevention and control strategies.

Constitutional MisMatch Repair Deficiency (CMMRD) is caused by homozygous or compound heterozygous germline variants in one of the mismatch repair (MMR) genes (MSH2, MSH6, PMS2, MLH1). This syndrome results in early onset colorectal cancer, leukemia and lymphoma, brain tumors and other malignancies. Children with CMMRD are at high risk of developing multiple cancers and cancer surveillance does not guarantee detection of cancer at a curable stage. The development of a preventive treatment strategy would be a major step forward. Long-term daily use of acetylsalicylic acid (ASA) has been shown to reduce cancer risk in individuals with Lynch syndrome (LS). LS is caused by heterozygous germline variants of MSH2, MSH6, PMS2 and MLH1 and characterized by an increased risk of developing colorectal and endometrial cancer at adult age. Here we discuss the potential use of ASA for cancer prevention in patients with CMMRD.