African American Cancer Risk Research Articles

Abstract C089: Residential segregation contributes to non-small cell lung cancer risk in African Americans in the southeastern US

Abstract Background: It remains unclear why African Americans (AA) have higher incidence of non-small cell lung cancer (NSCLC) and develop the disease 5 years earlier than Non-Hispanic Whites (NHW). Studies suggest that residential segregation drives NSCLC mortality disparities; however, there has been little investigation into whether residential segregation is also linked to the increased incidence of NSCLC risk among AAs. The lack of clarity regarding this link limits our understanding of possible societal determinants (SDH) related etiologies of the deadly disease. We aimed to evaluate the relationship between the isolation index – a well-known racial residential segregation metric that measures the level of exposure an average member of a specific demographic has with its own demographic – and NSCLC risk among AAs. We hypothesize that residential segregation will be associated with NSCLC risk in AAs but not in NHWs. Methods: We analyzed data from the Southern Community Cohort Study (SCCS), a large, prospective observational cohort study that recruited over 80,000 participants in the southeastern US from 2002-2009. The primary outcome is the NSCLC incidence. The SCCS is linked with cancer registries across the 12-state geographic catchment area, enabling the identification of NSCLC incidence. The isolation index was calculated using 2010 census tract data and ranges from 0 to 1, with a higher score representing higher isolation. The subdistribution hazard of NSCLC risk with the isolation index was estimated using Fine-Gray subdistribution hazard models, adjusted by demographic factors, smoking status and secondhand smoke exposure – all obtained from participant self-report surveys. Results: Of the 53,820 AA participants (mean age 50, 59% female, 37% never smokers), 1272 (2.4%) were diagnosed with NSCLC since enrollment. Of the 24,778 NHW participants (mean age 53, 61% female, 34% never smokers), 742 (3.0%) were diagnosed with NSCLC. Mean isolation index for AA = 0.71 (SD = 0.26), NHW= 0.25 (SD = 0.25). We found a significant association between residential segregation, as measured by the isolation index, and time to NSCLC in AAs. The adjusted subdistribution Hazard Ratio (sHR) of NSCLC risk for AAs with a 0.1 increase in isolation index was 1.03 (95% CI: 1.01, 1.05, p = 0.01). We did not detect a significant association in NHWs (p=0.88). The interaction between race and isolation index was not significant which may be due to lack of power. Conclusion: Our study is one of the first to document a link between racial residential segregation and NSCLC risk in AAs. This finding suggests that residential segregation, instituted and implemented by structural racism, embodies an environment that elevates NSCLC risk in AAs. Evaluation of structural racism across domains beyond segregation, in addition to the use of robust spatiotemporal methods, is required to further clarify the link with SDH, including structural racism and NSCLC risk. Such studies are essential to informing policies and interventions to improve population health and cancer prevention. Citation Format: Xiaoke Zou, Calvin Tribby, Richard Curley, Melinda Aldrich, Sophia Wang, Kimlin Ashing, Rick Kittles, Lennie Wong, Tarik Benmarhnia, Marta Jankowska, Loretta Erhunmwunsee. Residential segregation contributes to non-small cell lung cancer risk in African Americans in the southeastern US [abstract]. In: Proceedings of the 15th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2022 Sep 16-19; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2022;31(1 Suppl):Abstract nr C089.

Abstract 2262: Associations of plasma carotenes with lung cancer risk in a low-income population in the southeastern united states

Abstract Lung cancer is the second most common cancer and the leading cause of death from cancer in the U.S. Carotenes, with the properties of antioxidation and immunoregulation, have been demonstrated to have anti-carcinogenic effects. Previous prospective studies showed inverse associations of circulating α-carotene and β-carotene with lung cancer risk among European descendants and Asians. The associations of α-carotene and β-carotene isomers with lung cancer risk have not been investigated, particularly among African Americans (AAs) and low-income populations. We conducted a case-control study including 225 incident lung cancer cases and 429 controls, individually matched on age, race, and sex, nested in the Southern Community Cohort Study, including ~86,000 participants, two-thirds of whom are AAs. Carotene plasma concentrations were determined by a validated assay using high-pressure liquid chromatography with photo-diode array detection. Plasma trans-β-carotene (ORT3 VS. T1=0.54; 95% CI: 0.32-0.90; Ptrend=0.03), cis-β-carotene (ORT3 VS. T1=0.55; 95% CI: 0.32-0.93; Ptrend=0.03), and total β-carotene (ORT3 VS. T1=0.50; 95% CI: 0.30-0.84; Ptrend=0.01) were inversely associated with lung cancer risk. The associations remained significant after excluding cases diagnosed within the first year of follow-up. The inverse associations of plasma cis-β-carotene and total β-carotene with lung cancer risk were only observed among AAs and males. Plasma trans-α-carotene, trans-β-carotene, cis-β-carotene, and total β-carotene were inversely associated with lung cancer risk among those with lower body mass index (<median). In summary, plasma levels of β-carotenes were inversely associated with lung cancer risk in AA and low-income populations. Further studies with a larger sample size are warranted to confirm our findings. Citation Format: Yan Sun, Jie Wu, Hyung-Suk Yoon, Wei Zheng, Hui Cai, Maciej S. Buchowski, Adrian A. Franke, William J. Blot, Xiao-ou Shu, Qiuyin Cai. Associations of plasma carotenes with lung cancer risk in a low-income population in the southeastern united states [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 2262.

The oral microbiome in relation to pancreatic cancer risk in African Americans.

African Americans have the highest pancreatic cancer incidence of any racial/ethnic group in the United States. The oral microbiome was associated with pancreatic cancer risk in a recent study, but no such studies have been conducted in African Americans. Poor oral health, which can be a cause or effect of microbial populations, was associated with an increased risk of pancreatic cancer in a single study of African Americans. We prospectively investigated the oral microbiome in relation to pancreatic cancer risk among 122 African-American pancreatic cancer cases and 354 controls. DNA was extracted from oral wash samples for metagenomic shotgun sequencing. Alpha and beta diversity of the microbial profiles were calculated. Multivariable conditional logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for associations between microbes and pancreatic cancer risk. No associations were observed with alpha or beta diversity, and no individual microbial taxa were differentially abundant between cases and control, after accounting for multiple comparisons. Among never smokers, there were elevated ORs for known oral pathogens: Porphyromonas gingivalis (OR = 1.69, 95% CI: 0.80-3.56), Prevotella intermedia (OR = 1.40, 95% CI: 0.69-2.85), andTannerella forsythia (OR = 1.36, 95% CI: 0.66-2.77). Previously reported associations between oral taxa and pancreatic cancer were not present in this African-American population overall.

Association of oral microbiota with lung cancer risk in a low-income population in the Southeastern USA.

Oral microbiome plays an important role in oral health and systemic diseases, including cancer. We aimed to prospectively investigate the association of oral microbiome with lung cancer risk. We analyzed 156 incident lung cancer cases (73 European Americans and 83 African Americans) and 156 individually matched controls nested within the Southern Community Cohort Study. Oral microbiota were assessed using 16S rRNA gene sequencing in pre-diagnostic mouth rinse samples. Paired t test and the permutational multivariate analysis of variance test were used to evaluate lung cancer risk association with alpha diversity or beta diversity, respectively. Conditional logistic regression models were used to evaluate the association of individual bacterial abundance or prevalence with lung cancer risk. No significant differences were observed for alpha or beta diversity between lung cancer cases and controls. Abundance of families Lachnospiraceae_[XIV], Peptostreptococcaceae_[XI], and Erysipelotrichaceae and species Parvimonas micra was associated with decreased lung cancer risk, with odds ratios (ORs) and 95% confidence intervals (CIs) of 0.76 (0.59-0.98), 0.80 (0.66-0.97), 0.81 (0.67-0.99), and 0.83 (0.71-0.98), respectively (all p < 0.05). Prevalence of five pre-defined oral pathogens were not significantly associated with overall lung cancer risk. Prevalence of genus Bacteroidetes_[G-5] and species Alloprevotella sp._oral_taxon_912, Capnocytophaga sputigena, Lactococcus lactis, Peptoniphilaceae_[G-1] sp._oral_taxon_113, Leptotrichia sp._oral_taxon_225, and Fretibacterium fastidiosum was associated with decreased lung cancer risk, with ORs and 95% CIs of 0.55 (0.30-1.00), 0.36 (0.17-0.73), 0.53 (0.31-0.92), 0.43 (0.21-0.88), 0.43 (0.19-0.94), 0.57 (0.34-0.99), and 0.54 (0.31-0.94), respectively (all p < 0.05). Species L. sp._oral_taxon_225 was significantly associated with decreased lung cancer risk in African Americans (OR [95% CIs] 0.28 [0.12-0.66]; p = 0.00012). Results from this study suggest that oral microbiota may play a role in the development of lung cancer.

CEACAM Gene Family Mutations Associated With Inherited Breast Cancer Risk – A Comparative Oncology Approach to Discovery

IntroductionRecent studies comparing canine mammary tumors (CMTs) and human breast cancers have revealed remarkable tumor similarities, identifying shared expression profiles and acquired mutations. CMTs can also provide a model of inherited breast cancer susceptibility in humans; thus, we investigated breed-specific whole genome sequencing (WGS) data in search for novel CMT risk factors that could subsequently explain inherited breast cancer risk in humans.MethodsWGS was carried out on five CMT-affected Gold Retrievers from a large pedigree of 18 CMT-affected dogs. Protein truncating variants (PTVs) detected in all five samples (within human orthlogs) were validated and then genotyped in the 13 remaining CMT-affected Golden Retrievers. Allele frequencies were compared to canine controls. Subsequently, human blood-derived exomes from The Cancer Genome Atlas breast cancer cases were analyzed and allele frequencies were compared to Exome Variant Server ethnic-matched controls.ResultsCarcinoembryonic Antigen-related Cell Adhesion Molecule 24 (CEACAM24) c.247dupG;p.(Val83Glyfs∗48) was the only validated variant and had a frequency of 66.7% amongst the 18 Golden Retrievers with CMT. This was significant compared to the European Variation Archive (p-value 1.52 × 10–8) and non-Golden Retriever American Kennel Club breeds (p-value 2.48 × 10–5). With no direct ortholog of CEACAM24 in humans but high homology to all CEACAM gene family proteins, all human CEACAM genes were investigated for PTVs. A total of six and sixteen rare PTVs were identified in African and European American breast cancer cases, respectively. Single variant assessment revealed five PTVs associated with breast cancer risk. Gene-based aggregation analyses revealed that rare PTVs in CEACAM6, CEACAM7, and CEACAM8 are associated with European American breast cancer risk, and rare PTVs in CEACAM7 are associated with breast cancer risk in African Americans. Ultimately, rare PTVs in the entire CEACAM gene family are associated with breast cancer risk in both European and African Americans with respective p-values of 1.75 × 10–13 and 1.87 × 10–04.ConclusionThis study reports the first association of inherited CEACAM mutations and breast cancer risk, and potentially implicates the whole gene family in genetic risk. Precisely how these mutations contribute to breast cancer needs to be determined; especially considering our current knowledge on the role that the CEACAM gene family plays in tumor development, progression, and metastasis.

Invited Perspective: Air Pollution and Breast Cancer Risk: Current State of the Evidence and Next Steps.

Invited Perspective: Air Pollution and Breast Cancer Risk: Current State of the Evidence and Next Steps.

Coffee consumption and cancer risk in African Americans from the Southern Community Cohort Study

Coffee consumption has been associated with the risk of cancer at several anatomical sites, but the findings, mostly from studies of non-Hispanic whites and Asians, are inconsistent. The association between coffee consumption and the incidence of cancer has not been thoroughly examined in African Americans. We conducted a nested case–control study including 1801 cancer cases and 3337 controls among African Americans from the Southern Community Cohort Study (SCCS) to examine the association between coffee drinking, as assessed by a semi-quantitative food frequency questionnaire, and the risk of four common cancers (lung, prostate, breast, colorectal). We used logistic regression adjusted for age, sex and cancer-specific risk factors. Overall, only ≤ 9.5% of African American cases and controls from the SCCS drank regular or decaffeinated coffee ≥ 2 times/day. After adjustment for major cancer-specific risk factors, coffee consumption was not statistically significantly associated with the risk of lung, breast, colorectal, or prostate cancers (OR range 0.78–1.10; P ≥ 0.27 for ≥ 2 versus < 1 times/day) or overall cancer risk (OR 0.93; 95% CI 0.75–1.16; P = 0.52 for ≥ 2 versus < 1 times/day). Coffee consumption was not associated with the risk of cancer among African Americans in our study.

Genetic Polymorphisms in IL-10 Promoter Are Associated With Smoking and Prostate Cancer Risk in African Americans.

Even though prostate cancer (PCa) has good prognosis, there is a discrepancy in the risk among ethnic groups, with high morbidity in African American men. Single nucleotide polymorphisms (SNPs) in interleukin 10 (IL-10) have been associated with inflammation and cancer risk. We investigated the association of five SNPs in the IL-10 promoter with clinical features such as Gleason score and smoking. A total of 413 DNA samples were obtained from a nested case-control study of African American males who were genotyped for 5 SNPs utilizing pyrosequencing. Multiple and binary logistic regression models were applied to analyze the clinical and genotypic data. rs12122923 and rs1800871 were associated with PCa risk. Smoking was also found to increase the risk of PCa by 1.6-fold. rs1800893 was found to be associated with lower grades for prostate cancer. IL-10 promoter polymorphisms might be a risk factor for PCa development in smoking subjects and PCa progression.

Interactions of PVT1 and CASC11 on Prostate Cancer Risk in African Americans.

African American (AA) men have a higher risk of developing prostate cancer than white men. SNPs are known to play an important role in developing prostate cancer. The impact of PVT1 and its neighborhood genes (CASC11 and MYC) on prostate cancer risk are getting more attention recently. The interactions among these three genes associated with prostate cancer risk are understudied, especially for AA men. The objective of this study is to investigate SNP-SNP interactions in the CASC11-MYC-PVT1 region associated with prostate cancer risk in AA men. We evaluated 205 SNPs using the 2,253 prostate cancer patients and 2,423 controls and applied multiphase (discovery-validation) design. In addition to SNP individual effects, SNP-SNP interactions were evaluated using the SNP Interaction Pattern Identifier, which assesses 45 patterns. Three SNPs (rs9642880, rs16902359, and rs12680047) and 79 SNP-SNP pairs were significantly associated with prostate cancer risk. These two SNPs (rs16902359 and rs9642880) in CASC11 interacted frequently with other SNPs with 56 and 9 pairs, respectively. We identified the novel interaction of CASC11-PVT1, which is the most common gene interaction (70%) in the top 79 pairs. Several top SNP interactions have a moderate to large effect size (OR, 0.27-0.68) and have a higher prediction power to prostate cancer risk than SNP individual effects. Novel SNP-SNP interactions in the CASC11-MYC-PVT1 region have a larger impact than SNP individual effects on prostate cancer risk in AA men. This gene-gene interaction between CASC11 and PVT1 can provide valuable information to reveal potential biological mechanisms of prostate cancer development.

Cross-Cancer Pleiotropic Associations with Lung Cancer Risk in African Americans.

Identifying genetic variants with pleiotropic associations across multiple cancers can reveal shared biologic pathways. Prior pleiotropic studies have primarily focused on European-descent individuals. Yet population-specific genetic variation can occur, and potential pleiotropic associations among diverse racial/ethnic populations could be missed. We examined cross-cancer pleiotropic associations with lung cancer risk in African Americans. We conducted a pleiotropic analysis among 1,410 African American lung cancer cases and 2,843 controls. We examined 36,958 variants previously associated (or in linkage disequilibrium) with cancer in prior genome-wide association studies. Logistic regression analyses were conducted, adjusting for age, sex, global ancestry, study site, and smoking status. We identified three novel genomic regions significantly associated (FDR-corrected P <0.10) with lung cancer risk (rs336958 on 5q14.3, rs7186207 on 16q22.2, and rs11658063 on 17q12). On chromosome16q22.2, rs7186207 was significantly associated with reduced risk [OR = 0.43; 95% confidence interval (CI), 0.73-0.89], and functional annotation using GTEx showed rs7186207 modifies DHODH gene expression. The minor allele at rs336958 on 5q14.3 was associated with increased lung cancer risk (OR = 1.47; 95% CI, 1.22-1.78), whereas the minor allele at rs11658063 on 17q12 was associated with reduced risk (OR = 0.80; 95% CI, 0.72-0.90). We identified novel associations on chromosomes 5q14.3, 16q22.2, and 17q12, which contain HNF1B, DHODH, and HAPLN1 genes, respectively. SNPs within these regions have been previously associated with multiple cancers. This is the first study to examine cross-cancer pleiotropic associations for lung cancer in African Americans. Our findings demonstrate novel cross-cancer pleiotropic associations with lung cancer risk in African Americans.

Single nucleotide polymorphisms in the MYLKP1 pseudogene are associated with increased colon cancer risk in African Americans.

IntroductionPseudogenes are paralogues of functional genes historically viewed as defunct due to either the lack of regulatory elements or the presence of frameshift mutations. Recent evidence, however, suggests that pseudogenes may regulate gene expression, although the functional role of pseudogenes remains largely unknown. We previously reported that MYLKP1, the pseudogene of MYLK that encodes myosin light chain kinase (MLCK), is highly expressed in lung and colon cancer cell lines and tissues but not in normal lung or colon. The MYLKP1 promoter is minimally active in normal bronchial epithelial cells but highly active in lung adenocarcinoma cells. In this study, we further validate MYLKP1 as an oncogene via elucidation of the functional role of MYLKP1 genetic variants in colon cancer risk.MethodsProliferation and migration assays were performed in MYLKP1-transfected colon and lung cancer cell lines (H441, A549) and commercially-available normal lung and colon cells. Fourteen MYLKP1 SNPs (MAFs >0.01) residing within the 4 kb MYLKP1 promoter region, the core 1.4 kb of MYLKP1 gene, and a 4 kb enhancer region were selected and genotyped in a colorectal cancer cohort. MYLKP1 SNP influences on activity of MYLKP1 promoter (2kb) was assessed by dual luciferase reporter assay.ResultsCancer cell lines, H441 and A549, exhibited increased MYLKP1 expression, increased MYLKP1 luciferase promoter activity, increased proliferation and migration. Genotyping studies identified two MYLKP1 SNPs (rs12490683; rs12497343) that significantly increase risk of colon cancer in African Americans compared to African American controls. Rs12490683 and rs12497343 further increase MYLKP1 promoter activity compared to the wild type MYLKP1 promoter.ConclusionMYLKP1 is a cancer-promoting pseudogene whose genetic variants differentially enhance cancer risk in African American populations.

Abstract IA20: A coding region variant in the TP53 tumor-suppressor gene may underlie cancer disparities in African Americans

Abstract In addition to being frequently mutated in sporadic cancer, the p53 tumor suppressor also contains several coding region variants that alter function and can contribute to increased cancer risk. We previously published that the Pro47Ser variant of p53 exists in approximately 1-2% of individuals of African descent, and that this variation prevents a key phosphorylation event on p53, and reduces the ability of this protein to induce cell death (1). We recently published a mouse model for this variant, and show that this mouse develops a striking incidence of sporadic cancer, predominantly hepatocellular cancer but also including cancers of the pancreas, stomach, and intestine. In a cohort of African American women with breast cancer, we found evidence for an association of Pro47Ser with pre-menopausal cancer incidence (HR 1.7, p&amp;lt;0.025) (2). Mechanistically, we find that the Pro47Ser variant displays a very selective transcriptional defect compared to wild-type p53, for a subset of target genes involved in ferroptosis and metabolism (3). Metabolic studies on mouse and human cells, as well as our Pro47Ser mouse, indicate that there is a profound difference in metabolism, with cells and mice containing Pro47Ser showing a significant predilection for aerobic glycolysis instead of oxidative phosphorylation. Interestingly, this defect actually leads to an apparent increase in fitness in these mice. We recently conducted a drug screen to search for compounds that may be selectively efficacious in tumors containing the Pro47Ser variant; this analysis revealed several compounds with increased efficacy against Pro47Ser tumors, compared to identical tumors with wild-type p53 (4). Our combined data suggest that the Pro47Ser variant may underlie increased cancer risk in African Americans, and that we may be able to personalize therapy for individuals containing this variant. 1. Li X, Dumont P, Della Pietra A, Shetler C, Murphy ME. The codon 47 polymorphism in p53 is functionally significant. J Biol Chem 2005;280(25):24245-51. PubMed PMID: 15851479. 2. Murphy ME, Liu S, Yao S, et al. A functionally significant SNP in TP53 and breast cancer risk in African-American women. NPJ Breast Cancer 2017;3:5. PubMed Central PMCID: PMC5445618. 3. Jennis M, Kung CP, Basu S, et al. An African-specific polymorphism in the TP53 gene impairs p53 tumor suppressor function in a mouse model. Genes Dev 2016;30(8):918-30. PubMed Central PMCID: PMC4840298. 4. Basu S, Barnoud T, Kung CP, Reiss M, Murphy ME. The African-specific S47 polymorphism of p53 alters chemosensitivity. Cell Cycle 2016;15(19):2557-60. PubMed Central PMCID: PMC5053554. Citation Format: Maureen E. Murphy. A coding region variant in the TP53 tumor-suppressor gene may underlie cancer disparities in African Americans [abstract]. In: Proceedings of the AACR Special Conference: Advances in Breast Cancer Research; 2017 Oct 7-10; Hollywood, CA. Philadelphia (PA): AACR; Mol Cancer Res 2018;16(8_Suppl):Abstract nr IA20.

Androgen receptor gene CAG repeat polymorphism and ovarian cancer risk: A meta-analysis.

Ovarian cancer is one of the common gynecological malignancies worldwide. It is usually diagnosed at a later stage, thus missing the best opportunity for treatment. Despite the advancement of ovarian cancer treatment, the prognosis is still poor. Androgen receptor (AR) may play a role in ovarian carcinogenesis. Previous studies regarding the association between AR CAG repeat length and ovarian cancer risk reported inconsistent results. Therefore, we conducted a meta-analysis to evaluate the association between AR CAG repeat length and ovarian cancer risk following the MOOSE guidelines. PubMed, Web of Science, EBSCO and other databases were searched up to September 15th 2016. Case control studies with clear definition of CAG repeat length and detailed genotype information were included. Two authors independently reviewed and extracted data. Pooled analysis and subgroup analysis stratified by ethnicity were performed for different genetic models. Begg's funnel plot and Egger's test were performed for publication bias estimation. Overall, there was no association between the AR CAG repeat polymorphism and ovarian cancer risk. However, short CAG repeat polymorphism was associated with increased ovarian cancer risk in African Americans and Chinese under the dominant model, whereas a reverse association was observed in Caucasians and Italians under the other three models. Our study results should be interpreted with caution. Further well-designed epidemiological and functional studies are needed to elucidate the role of AR in ovarian carcinogenesis.

Genome-wide association study confirms lung cancer susceptibility loci on chromosomes 5p15 and 15q25 in an African-American population

ObjectivesGenome-wide association studies (GWAS) of lung cancer have identified regions of common genetic variation with lung cancer risk in Europeans who smoke and never-smoking Asian women. This study aimed to conduct a GWAS in African Americans, who have higher rates of lung cancer despite smoking fewer cigarettes per day when compared with Caucasians. This population provides a different genetic architecture based on underlying African ancestry allowing the identification of new regions and exploration of known regions for finer mapping. Materials and methodsWe genotyped 1,024,001 SNPs in 1737 cases and 3602 controls in stage 1, followed by a replication phase of 20 SNPs (p<1.51×10−5) in an independent set of 866 cases and 796 controls in stage 2. Results and conclusionIn the combined analysis, we confirmed two loci to be associated with lung cancer that achieved the threshold of genome-wide significance: 15q25.1 marked by rs2036527 (p=1.3×10−9; OR=1.32; 95% CI=1.20–1.44) near CHRNA5, and 5p15.33 marked by rs2853677 (p=2.8×10−9; OR=1.28; 95% CI=1.18–1.39) near TERT. The association with rs2853677 is driven by the adenocarcinoma subtype of lung cancer (p=1.3×10−8; OR=1.37; 95% CI=1.23–1.54). No SNPs reached genome-wide significance for either of the main effect models examining smoking − cigarettes per day and current or former smoker. Our study was powered to identify strong risk loci for lung cancer in African Americans; we confirmed results previously reported in African Americans and other populations for two loci near plausible candidate genes, CHRNA5 and TERT, on 15q25.1 and 5p15.33 respectively, are associated with lung cancer. Additional work is required to map and understand the biological underpinnings of the strong association of these loci with lung cancer risk in African Americans.

Abstract B16: IL-10 promoter polymorphisms are associated with prostate cancer risk in African Americans

Abstract Background: African American men have the highest rates of prostate cancer (PCa) worldwide and immunogenetic studies suggest emerging evidence that prostate inflammation may contribute to prostatic carcinogenesis. Since genetic susceptibility is an etiological factor in PCa, we hypothesize that sequence variants in the promoter region of the IL-10 gene that regulate pro inflammatory cytokines, may modify individual susceptibility to this disease. Methods: four SNPs in the promoter regions with allele frequency differences between Europeans and West Africans were genotyped using pyrosequencing in 538 unrelated men enrolled in a PCa genetic association study at the Howard University Hospital between 2000-2004. Results: SNP rs12122923 was found to have the strongest association using the dominant (p=0.048) and the log additive (p=0.029) genetic models. rs1800871 was found to be associated with PCa using the log additive model(p=0.057). However, after adjusting for age, both SNPs became insignificantly associated with PCa. Conclusions: This study showed an association between IL-10 promoter SNP variation and PCa. This supports the hypothesis that genetic variation in the inflammatory process can contribute to prostate cancer susceptibility. Research supported in part by NIH/NIGMS/MBRS/SCORE grant # S06GM008016. Citation Format: Muneer M. Abbas, Tshela Mason, Luisel Ricks-Santi, Victor Apprey, Rick Kittles, Chiledum Ahaghotu, Georgia Dunston. IL-10 promoter polymorphisms are associated with prostate cancer risk in African Americans. [abstract]. In: Proceedings of the Eighth AACR Conference on The Science of Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; Nov 13-16, 2015; Atlanta, GA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2016;25(3 Suppl):Abstract nr B16.

Abstract IA03: Lung cancer risk in African Americans: Familial aggregation and genetic susceptibility

Abstract IA03: Lung cancer risk in African Americans: Familial aggregation and genetic susceptibility

Abstract C72: Improving the accuracy and diagnostic power of prostate biopsy for African American patients: The Birmingham Alabama Prostate Cancer (BAPrCa) Consortium

Abstract Study Purpose: Both incidence and mortality data show that the burden of prostate cancer (PrCa) is greater in African Americans (AA) than in European Americans (EA). Socioeconomic factors contribute to this health disparity, but do not fully account for observations that AA are more likely than others to be diagnosed with more aggressive and life threatening forms of PrCa. Prostate biopsies usually establish the diagnosis of PrCa and are used to estimate the extent of the disease (based on the number and location of cores with cancer and involvement of individual cores) and its potential aggressiveness (based on Gleason scores). Health policy groups recommend that men with limited low grade prostate cancer be managed by active surveillance (AS) rather than immediate surgical or radiation treatment. However, the standard-of-care prostate biopsy is limited by sampling error and the possibility that a high grade PrCa might have been missed is a significant concern for many patients who are considering AS; this concern is heightened for AA because of their higher risk of aggressive disease. Moreover, AA are more likely to be diagnosed with high grade/high stage prostate cancer that is not treated surgically and thus not well represented in molecular studies that utilize radical prostatectomy specimens. Our research team established the Birmingham Alabama Prostate Cancer (BAPrCa) Consortium with a major focus on the molecular analysis of prostate biopsies in order to increase the clinically actionable information that can be obtained from these specimens. We use an ancestry-informed approach that is specifically designed to improve the accuracy and diagnostic power of prostate biopsy for AA patients. Experimental Procedures: The BAPrCa Consortium implemented an innovative prostate biopsy “tissue print” technology that permits collection of snap-frozen nitrocellulose blots of biopsy cores without diagnostically compromising these specimens. Tissue prints provide high quality RNA and DNA from biopsies from the full range of patients, including AAs whose cancer is too advanced at diagnosis for radical prostatectomy; this permits the molecular characterization of PrCa subtypes in men diagnosed with high volume/high grade disease who have not been adequately represented in previous molecular profiling studies. Our BAPrCa research protocols include informed consent for genetic ancestry admixture studies. Gene expression analysis of prostate biopsy tissue prints is correlated with histopathology and multiparametric prostate MRI. Results: Our data suggest that in the Birmingham area, higher prostate cancer risk in AA is associated with increasing proportion of West African (WA) ancestry, which may reflect the prevalence of population-specific genetic mutations or variations that contribute to the development of more aggressive disease. As a group, the men diagnosed with high grade PrCa showed a significantly higher level of WA ancestry than the men diagnosed with no cancer (P = 0.001). A similar pattern is observed in comparisons of AA men diagnosed with high grade cancer vs low grade PrCa. Inasmuch as our AIMs genotyping panel uses a small number of well-established AIMS markers, our observation of significantly increased risk of PrCa in AA men with high %WA AIMS ancestry may, if confirmed, have immediate potential clinical applications for improving prostate cancer screening and active surveillance. Moreover, gene expression profiles of biopsies from BAPrCa patients diagnosed with high volume/high grade PrCa revealed two subtypes of high grade PrCa with striking differences in the pathways that drive a shift in tumor fatty acid metabolism; one is a fatty acid synthase (FASN) dominant phenotype and the other a previously unrecognized fatty acid binding protein (FABP5) dominant phenotype. Our data suggest that the FABP5 dominant PrCa subtype is more common in AA and the FASN dominant subtype more common in EA. These findings may provide the basis for more effective dietary interventions and targeted therapies for AA and EA patients with high grade PrCa. Conclusions: By utilizing innovative tissue print techniques for the molecular analyses of prostate biopsies and using an ancestry informed approach in our study designs, the Birmingham Alabama Prostate Cancer (BAPrCa) Consortium has identified new and potentially actionable PrCa signatures that may improve the accuracy and diagnostic power of prostate biopsy for AA patients. Citation Format: Sandra M. Gaston, Soroush Rais-Bahrami, Rick Kittles, Kerry Dehimer, Dennis Otali, Jeffrey W. Nix, Peter N. Kolettis, George Adams, William E. Grizzle. Improving the accuracy and diagnostic power of prostate biopsy for African American patients: The Birmingham Alabama Prostate Cancer (BAPrCa) Consortium. [abstract]. In: Proceedings of the Eighth AACR Conference on The Science of Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; Nov 13-16, 2015; Atlanta, GA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2016;25(3 Suppl):Abstract nr C72.

A review of hair product use on breast cancer risk in African American women.

The incidence rate of breast cancer for African American women has recently converged with that of non‐Hispanic White women in the United States, although African Americans have a higher mortality rate due to this disease. Although most research exploring health disparities associated with this phenomenon has focused on differences between women based on biology and behavior, both the academic and lay communities have begun to explore the potential role of environmental exposure to estrogen and endocrine disrupting chemicals (EDCs). This study reviews the current state of the science associating one such means of exposure, hair products containing EDCs, with breast cancer risk in African American women. We found a growing body of evidence linking: (1) environmental estrogen and EDC exposures to breast cancer risk, (2) the presence of such chemicals in personal care products, including hair products, and (3) the use of certain hair products with potential breast cancer risk in African Americans. At the same time, there is also increasing concern in the lay community about this risk. These results indicate the need for additional research, and the opportunity to benefit from strategic partnerships in community‐collaborative approaches in order to better understand the potential “cost of beauty.”

Gene by Environment Investigation of Incident Lung Cancer Risk in African-Americans

BackgroundGenome-wide association studies have identified polymorphisms linked to both smoking exposure and risk of lung cancer. The degree to which lung cancer risk is driven by increased smoking, genetics, or gene–environment interactions is not well understood. MethodsWe analyzed associations between 28 single nucleotide polymorphisms (SNPs) previously associated with smoking quantity and lung cancer in 7156 African-American females in the Women's Health Initiative (WHI), then analyzed main effects of top nominally significant SNPs and interactions between SNPs, cigarettes per day (CPD) and pack-years for lung cancer in an independent, multi-center case–control study of African-American females and males (1078 lung cancer cases and 822 controls). FindingsNine nominally significant SNPs for CPD in WHI were associated with incident lung cancer (corrected p-values from 0.027 to 6.09×10−5). CPD was found to be a nominally significant effect modifier between SNP and lung cancer for six SNPs, including CHRNA5 rs2036527[A](betaSNP*CPD=−0.017, p=0.0061, corrected p=0.054), which was associated with CPD in a previous genome-wide meta-analysis of African-Americans. InterpretationThese results suggest that chromosome 15q25.1 variants are robustly associated with CPD and lung cancer in African-Americans and that the allelic dose effect of these polymorphisms on lung cancer risk is most pronounced in lighter smokers.

Fat, fibre and cancer risk in African Americans and rural Africans.

Rates of colon cancer are much higher in African Americans (65:100,000) than in rural South Africans (<5:100,000). The higher rates are associated with higher animal protein and fat and lower fiber consumption, higher colonic secondary bile acids, lower colonic short chain fatty acid quantities and higher mucosal proliferative biomarkers of cancer risk in otherwise healthy middle aged volunteers. Here we investigate further the role of fat and fiber in this association. We performed two-week food exchanges in subjects from the same populations, where African Americans were fed a high-fiber, lowfat African-style diet, and rural Africans a high-fat low-fiber western-style diet under close supervision. In comparison to their usual diets, the food changes resulted in remarkable reciprocal changes in mucosal biomarkers of cancer risk and in aspects of the microbiota and metabolome known to affect cancer risk, best illustrated by increased saccharolytic fermentation and butyrogenesis and suppressed secondary bile acid synthesis in the African Americans.