Cancer Epidemiology Biomarkers & Prevention最新文献

Background: Rapid growth in the number of U.S. cancer survivors drives the need for ongoing research efforts to improve outcomes and experiences after cancer. Here we describe the University of North Carolina (UNC) Cancer Survivorship Cohort, a medical center-based cohort of adults with cancer that integrates medical record-abstracted cancer information, patient-reported outcomes, and biologic specimens.

Methods: Participants ages 18+ were recruited from UNC oncology clinics between April 2010 and August 2016. After enrollment, participants completed questionnaires on a range of topics including demographics, health history, health care access and utilization, quality of life, and symptoms. Blood samples and tumor tissue specimens were collected and processed by study staff, and cancer characteristics and other clinical data were abstracted from electronic medical records. Participants consented to recontact for future studies and linkage of their data with other data resources.

Results: In total, 3,999 participants with a cancer diagnosis were enrolled in the cohort. The most common cancer types among those enrolled included breast (N=866), uterine (N=458), colorectal (N=300), prostate (N=296), and head and neck (N=248). Blood specimens were collected for 3,027 (76%). Additional participants without cancer (N=1,299) were also enrolled, and the majority (62%) provided biospecimen samples.

Conclusions: We encourage wide collaboration with investigators across institutions seeking to advance research in cancer survivorship. Procedures are in place to support proposals for use of existing or linked data and for proposals that require participant recontact or analysis of biospecimens.

Impact: The UNC Cancer Survivorship Cohort is a unique resource for cancer survivorship research.

Background: Previous survival studies on hepatocellular carcinoma (HCC) by etiology are limited to hospital-based series, restricted cohorts, and monolithic etiological categories. We studied population-based survival by seven mutually exclusive HCC etiologic groups-standalone hepatitis-C virus (HCV), hepatitis-B virus (HBV), alcohol-related liver disease (ALD), non-alcoholic fatty liver disease (NAFLD), and dual etiology HCV&HBV, HCV&ALD, and HBV&ALD-accounting for clinical and socio-demographic characteristics.

Methods: All HCC cases diagnosed during 2005-2018 from the Florida Cancer Registry were linked for etiology using statewide discharge and viral hepatitis data. We performed cause-specific survival analysis including Cox regression for the matched 15,616 cases by HCC etiology.

Results: The leading etiology was HCV only (n=4,983; 31.9%); the leading dual etiology was HCV&ALD (n=2,552; 16.3%). Five-year adjusted survival was low, 17.6% overall and <22% across all HCC etiologies; yet ALD-related etiologies [ALD only (14.4%; 95%CI:12.7-16.0), HCV&ALD (10.2%; 95%CI:8.7-11.7), HBV&ALD (8.2%; 95%CI:2.2-14.1)] showed lower survival than non-ALD causes-HCV only, HBV only, and NAFLD only. After adjustment for clinical and socio-demographic covariates, ALD- and HBV&ALD-HCC had 1.20 (95%CI:1.13-1.27) and 1.28 (95%CI:1.06-1.54) times higher risk of death, compared to those with HCV only-HCC.

Conclusions: ALD only and dual etiologies involving ALD show worse prognosis for HCC, compared to viral etiology alone. To increase survival, improved screening and treatment are needed for patients with multiple HCC risk factors.

Impact: Understanding US disparities in HCC survival by etiology can help guide the identification of etiologically specific biomarkers and potential therapeutic targets and inform public health measures.

Background: Fertility counseling is recommended for adolescent and young adult women facing gonadotoxic cancer therapy. However, fertility care is subspecialized medical care offered at a limited number of institutions, making geographic access a potential barrier to guideline-concordant care. We assessed the relationship between geographic access and receipt of fertility counseling among adolescent and young adult women with cancer.

Methods: Using data from the North Carolina Central Cancer Registry, we identified women diagnosed with lymphoma, gynecologic cancer, or breast cancer at ages 15 to 39 years during 2004 to 2015. Eligible women were invited to complete an online survey on various topics, including fertility counseling. Geographic access was measured, using geocoded addresses, as vehicular travel time from residence to the nearest fertility clinic available at diagnosis. Multivariable regression models were used to examine the association between travel time and receipt of fertility counseling by provider type: health care provider versus fertility specialist.

Results: Analyses included 380 women. The median travel time to a fertility clinic was 31 (IQR: 17-71) minutes. Overall, 75% received fertility counseling from a health care provider and 16% by a fertility specialist. Women who lived ≥30 minutes from a clinic were 13% less likely to receive fertility counseling by a health care provider (prevalence ratio: 0.87; 95% confidence interval, 0.75-1.00) and 49% less likely to receive counseling by a fertility specialist (prevalence ratio: 0.51; 95% confidence interval, 0.28-0.93).

Conclusions: Women who lived further away from fertility clinics were less likely to receive fertility counseling.

Impact: Interventions to improve access to fertility counseling should include strategies to alleviate the burden of geographic access.

Background: African Americans have higher incidence and mortality from lung cancer than non-Hispanic Whites, but investigations into differences in immune response have been minimal. Therefore, we compared components of the tumor microenvironment among African Americans and non-Hispanic Whites diagnosed with non-small cell lung cancer based on PDL1 or tertiary lymphoid structure (TLS) status to identify differences of translational relevance.

Methods: Using a cohort of 280 patients with non-small cell lung cancer from the Inflammation, Health, Ancestry, and Lung Epidemiology study (non-Hispanic White: n = 155; African American: n = 125), we evaluated PDL1 tumor proportion score (<1% vs. ≥1%) and TLS status (presence/absence), comparing differences within the tumor microenvironment based on immune cell distribution and differential expression of genes.

Results: Tumors from African Americans had a higher proportion of plasma cell signatures within the tumor microenvironment than non-Hispanic Whites. In addition, gene expression patterns in African American PDL1-positive samples suggest that these tumors contained greater numbers of γδ T cells and resting dendritic cells, along with fewer CD8+ T cells after adjusting for age, sex, pack-years, stage, and histology. Investigation of differential expression of B cell/plasma cell-related genes between the two patient populations revealed that two immunoglobulin genes (IGKV2-29 and IGLL5) were associated with decreased mortality risk in African Americans.

Conclusions: In the first known race-stratified analysis of tumor microenvironment components in lung cancer based on PDL1 expression or TLS status, differences within the immune cell composition and transcriptomic signature were identified that may have therapeutic implications.

Impact: Future investigation of racial variation within the tumor microenvironment may help direct the use of immunotherapy.

Background: Pancreatic cancer is a leading cause of cancer-related death globally. Risk factors for pancreatic cancer include common genetic variants and potentially heavy alcohol consumption. We assessed if genetic variants modify the association between heavy alcohol consumption and pancreatic cancer risk.

Methods: We conducted a genome-wide interaction analysis of single-nucleotide polymorphisms (SNP) by heavy alcohol consumption (more than three drinks per day) for pancreatic cancer in European ancestry populations from genome-wide association studies. Our analysis included 3,707 cases and 4,167 controls from case-control studies and 1,098 cases and 1,162 controls from cohort studies. Fixed-effect meta-analyses were conducted.

Results: A potential novel region of association on 10p11.22, lead SNP rs7898449 (interaction P value (Pinteraction) = 5.1 × 10-8 in the meta-analysis; Pinteraction = 2.1 × 10-9 in the case-control studies; Pinteraction = 0.91 in the cohort studies), was identified. An SNP correlated with this lead SNP is an expression quantitative trait locus for the neuropilin 1 gene. Of the 17 genomic regions with genome-wide significant evidence of association with pancreatic cancer in prior studies, we observed suggestive evidence that heavy alcohol consumption modified the association for one SNP near LINC00673, rs11655237 on 17q25.1 (Pinteraction = 0.004).

Conclusions: We identified a novel genomic region that may be associated with pancreatic cancer risk in conjunction with heavy alcohol consumption located near an expression quantitative trait locus for neuropilin 1, a protein that plays an important role in the development and progression of pancreatic cancer.

Impact: This work can provide insights into the etiology of pancreatic cancer, particularly in heavy drinkers.

Background: Prenatal folate supplementation has been consistently associated with a reduced risk of childhood acute lymphoblastic leukemia (ALL). Previous germline genetic studies examining the one carbon (folate) metabolism pathway were limited in sample size, scope, and population diversity and led to inconclusive results.

Methods: We evaluated whether ∼2,900 single-nucleotide polymorphisms (SNP) within 46 candidate genes involved in the folate metabolism pathway influence the risk of childhood ALL, using genome-wide data from nine case-control studies in the Childhood Cancer and Leukemia International Consortium (n = 9,058 cases including 4,510 children of European ancestry, 3,018 Latinx, and 1,406 Asians, and 92,364 controls). Each study followed a standardized protocol for quality control and imputation of genome-wide data and summary statistics were meta-analyzed for all children combined and by major ancestry group using METAL software.

Results: None of the selected SNPs reached statistical significance, overall and for major ancestry groups (using adjusted Bonferroni P-value of 5 × 10-6 and less-stringent P-value of 3.5 × 10-5 accounting for the number of "independent" SNPs). None of the 10 top (nonsignificant) SNPs and corresponding genes overlapped across ancestry groups.

Conclusions: This large meta-analysis of original data does not reveal associations between many common genetic variants in the folate metabolism pathway and childhood ALL in various ancestry groups.

Impact: Genetic variants in the folate pathway alone do not appear to substantially influence childhood acute lymphoblastic leukemia risk. Other mechanisms such as gene-folate interaction, DNA methylation, or maternal genetic effects may explain the observed associations with self-reported prenatal folate intake.