Interethnic differences in pancreatic cancer incidence and risk factors: The Multiethnic Cohort.

While disparity in pancreatic cancer incidence between blacks and whites has been observed, few studies have examined disparity in other ethnic minorities. We evaluated variations in pancreatic cancer incidence and assessed the extent to which known risk factors account for differences in pancreatic cancer risk among African Americans, Native Hawaiians, Japanese Americans, Latino Americans, and European Americans in the Multiethnic Cohort Study. Risk factor data were obtained from the baseline questionnaire. Cox regression was used to estimate the relative risks (RRs) and 95% confidence intervals (CIs) for pancreatic cancer associated with risk factors and ethnicity. During an average 16.9-year follow-up, 1,532 incident pancreatic cancer cases were identified among 184,559 at-risk participants. Family history of pancreatic cancer (RR 1.97, 95% CI 1.50-2.58), diabetes (RR 1.32, 95% CI 1.14-1.54), body mass index ≥30 kg/m2 (RR 1.25, 95% CI 1.08-1.46), current smoking (<20 pack-years RR 1.43, 95% CI 1.19-1.73; ≥20 pack-years RR 1.76, 95% CI 1.46-2.12), and red meat intake (RR 1.17, 95% CI 1.00-1.36) were associated with pancreatic cancer. After adjustment for these risk factors, Native Hawaiians (RR 1.60, 95% CI 1.30-1.98), Japanese Americans (RR 1.33, 95% CI 1.15-1.54), and African Americans (RR 1.20, 95% CI 1.01-1.42), but not Latino Americans (RR 0.90, 95% CI 0.76-1.07), had a higher risk of pancreatic cancer compared to European Americans. Interethnic differences in pancreatic cancer risk are not fully explained by differences in the distribution of known risk factors. The greater risks in Native Hawaiians and Japanese Americans are new findings and elucidating the causes of these high rates may improve our understanding and prevention of pancreatic cancer

Mediastinal Germ Cell Tumors: Updates in Diagnosis and Management

Primary mediastinal nonseminomatous germ cell tumors represent a rare but important malignancy that occurs in otherwise young and healthy patients. Treatment is challenging and involves cisplatin-based chemotherapy followed by surgery to remove residual disease. Avoiding bleomycin-containing chemotherapy in the treatment of primary mediastinal nonseminomatous germ cell tumors is important. Prechemotherapy and postchemotherapy pathology as well as postoperative serum tumor markers are independent predictors of long-term survival

Improved Imputation of Common and Uncommon Single Nucleotide Polymorphisms (SNPs) with a New Reference Set

Statistical imputation of genotype data is an important technique for analysis of genome-wide association studies (GWAS). We have built a reference dataset to improve imputation accuracy for studies of individuals of primarily European descent using genotype data from the Hap1, Omni1, and Omni2.5 human SNP arrays (Illumina). Our dataset contains 2.5-3.1 million variants for 930 European, 157 Asian, and 162 African/African-American individuals. Imputation accuracy of European data from Hap660 or OmniExpress array content, measured by the proportion of variants imputed with R^2^>0.8, improved by 34%, 23% and 12% for variants with MAF of 3%, 5% and 10%, respectively, compared to imputation using publicly available data from 1,000 Genomes and International HapMap projects. The improved accuracy with the use of the new dataset could increase the power for GWAS by as much as 8% relative to genotyping all variants. This reference dataset is available to the scientific community through the NCBI dbGaP portal. Future versions will include additional genotype data as well as non-European populations

Leveraging population admixture to characterize the heritability of complex traits.

Despite recent progress on estimating the heritability explained by genotyped SNPs (h(2)g), a large gap between h(2)g and estimates of total narrow-sense heritability (h(2)) remains. Explanations for this gap include rare variants or upward bias in family-based estimates of h(2) due to shared environment or epistasis. We estimate h(2) from unrelated individuals in admixed populations by first estimating the heritability explained by local ancestry (h(2)γ). We show that h(2)γ = 2FSTCθ(1 - θ)h(2), where FSTC measures frequency differences between populations at causal loci and θ is the genome-wide ancestry proportion. Our approach is not susceptible to biases caused by epistasis or shared environment. We applied this approach to the analysis of 13 phenotypes in 21,497 African-American individuals from 3 cohorts. For height and body mass index (BMI), we obtained h(2) estimates of 0.55 ± 0.09 and 0.23 ± 0.06, respectively, which are larger than estimates of h(2)g in these and other data but smaller than family-based estimates of h(2)

Patient-Reported Outcomes Integrated Within an Electronic Medical Record in Patients With Head and Neck Cancer

PURPOSE: Patient-reported outcome (PRO) tools lead to clinical benefits, including improved overall survival for patients with cancer. However, routine implementation of PROs in clinical practice within the electronic medical record (EMR) by integrated health care delivery systems remains limited. We studied the use of a PRO tool for patients with head and neck cancer (HNC) integrated in an EMR at Kaiser Permanente in Northern California. METHODS: Between August 2017 and December 2019, patients with newly diagnosed HNC were surveyed at baseline, then every 3 months using the Functional Assessment of Cancer Therapy-General 7 and Functional Assessment of Cancer Therapy-Head and Neck (version 4). A medical assistant performed a baseline survey on diagnosis and then notified patients electronically per surveillance protocol. Patients who did not respond to online PRO surveys could complete them via telephone or in-person appointments with medical assistants. Abnormal findings on PRO surveys were referred to appropriate members of the care team or the treating Otolaryngology-Head and Neck Surgery physicians. RESULTS: Two hundred ninety patients received baseline surveys. Patients received up to a maximum of eight subsequent surveys. Of a total of 597 electronic surveys, 585 (97.9%) were completed. The percentage of patients completing each interval survey ranged from 92% to 100%. Multivariate Poisson regression analysis showed patients with English as their primary language and an online secure account were the most likely to complete surveys compared with those patients with non-English as a primary language and without an online account. CONCLUSION: PRO tools can be effectively used within the EMR for patients with HNC with a high response rate provided there is strong engagement from a dedicated member of the care team. This has important implications for designing clinical trials and symptom monitoring in clinical practices that incorporate EMRs

Leveraging population admixture to characterize the heritability of complex traits

Despite recent progress on estimating the heritability explained by genotyped SNPs (hg2), a large gap between hg2 and estimates of total narrow-sense heritability (h2) remains. Explanations for this gap include rare variants, or upward bias in family-based estimates of h2 due to shared environment or epistasis. We estimate h2 from unrelated individuals in admixed populations by first estimating the heritability explained by local ancestry (hγ2). We show that hγ2 = 2FSTCθ(1−θ)h2, where FSTC measures frequency differences between populations at causal loci and θ is the genome-wide ancestry proportion. Our approach is not susceptible to biases caused by epistasis or shared environment. We examined 21,497 African Americans from three cohorts, analyzing 13 phenotypes. For height and BMI, we obtained h2 estimates of 0.55 ± 0.09 and 0.23 ± 0.06, respectively, which are larger than estimates of hg2 in these and other data, but smaller than family-based estimates of h2

Outcomes following surgery for primary mediastinal nonseminomatous germ cell tumors in the cisplatin era

Objective Treatment of primary mediastinal nonseminomatous germ cell tumors involves cisplatin-based chemotherapy followed by surgery to remove residual disease. We undertook a study to determine short and long-term outcomes. Methods A retrospective analysis of patients with primary mediastinal nonseminomatous germ cell tumors who underwent surgery at our institution from 1982 to 2017 was performed. Results A total of 255 patients (mean age, 29.2 years) were identified. Acute respiratory distress syndrome occurred postoperatively in 27 patients (10.9%), which was responsible for all 11 (4.3%) postoperative deaths. Of patients who developed acute respiratory distress syndrome, more patients received bleomycin-containing chemotherapy (25 out of 169; 14.8%) than non-bleomycin regimens (2 out of 77; 2.6%) (P = .004). With respect to variables independently predictive of long-term survival, evidence of choriocarcinoma before chemotherapy (n = 12) was determined to be an adverse factor (P = .006). In contrast, biopsy-proven elements of seminoma (n = 34) were predictive of improved survival (P = .04). The worst pathology identified in the residual mediastinal mass after chemotherapy was necrosis in 61 patients (25.0%), teratoma in 84 patients (34.4%), and malignant (persistent germ cell or non–germ cell cancer) in 97 patients (39.8%), which influenced overall survival (P 50% of the residual mass (n = 47) had a 2.3-fold increased risk of death compared with ≤50% malignancy (n = 45; P = .008). Finally, elevated postoperative serum tumor markers (n = 40) was significantly predictive of adverse survival (P < .001). Conclusions In the treatment of primary mediastinal nonseminomatous germ cell tumors, avoiding bleomycin-containing chemotherapy is important. Pre- and postchemotherapy pathology and postoperative serum tumor markers are independent predictors of long-term survival