Publications by authors named "William J Blot"

287 Publications

Performance of African-ancestry-specific polygenic hazard score varies according to local ancestry in 8q24.

Prostate Cancer Prostatic Dis 2021 Jun 14. Epub 2021 Jun 14.

School of Public Health, Louisiana State University Health Sciences Center, New Orleans, LA, USA.

Background: We previously developed an African-ancestry-specific polygenic hazard score (PHS46+African) that substantially improved prostate cancer risk stratification in men with African ancestry. The model consists of 46 SNPs identified in Europeans and 3 SNPs from 8q24 shown to improve model performance in Africans. Herein, we used principal component (PC) analysis to uncover subpopulations of men with African ancestry for whom the utility of PHS46+African may differ.

Materials And Methods: Genotypic data were obtained from the PRACTICAL consortium for 6253 men with African genetic ancestry. Genetic variation in a window spanning 3 African-specific 8q24 SNPs was estimated using 93 PCs. A Cox proportional hazards framework was used to identify the pair of PCs most strongly associated with the performance of PHS46+African. A calibration factor (CF) was formulated using Cox coefficients to quantify the extent to which the performance of PHS46+African varies with PC.

Results: CF of PHS46+African was strongly associated with the first and twentieth PCs. Predicted CF ranged from 0.41 to 2.94, suggesting that PHS46+African may be up to 7 times more beneficial to some African men than others. The explained relative risk for PHS46+African varied from 3.6% to 9.9% for individuals with low and high CF values, respectively. By cross-referencing our data set with 1000 Genomes, we identified significant associations between continental and calibration groupings.

Conclusion: We identified PCs within 8q24 that were strongly associated with the performance of PHS46+African. Further research to improve the clinical utility of polygenic risk scores (or models) is needed to improve health outcomes for men of African ancestry.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41391-021-00403-7DOI Listing
June 2021

A Pooled Case-only Analysis of Reproductive Risk Factors and Breast Cancer Subtype Among Black Women in the Southeastern United States.

Cancer Epidemiol Biomarkers Prev 2021 May 4. Epub 2021 May 4.

Vanderbilt-Ingram Cancer Center, Nashville, Tennessee.

Background: We investigated the association between reproductive risk factors and breast cancer subtype in Black women. On the basis of the previous literature, we hypothesized that the relative prevalence of specific breast cancer subtypes might differ according to reproductive factors.

Methods: We conducted a pooled analysis of 2,188 (591 premenopausal, 1,597 postmenopausal) Black women with a primary diagnosis of breast cancer from four studies in the southeastern United States. Breast cancers were classified by clinical subtype. Case-only polytomous logistic regression models were used to estimate ORs and 95% confidence intervals (CI) for HER2 and triple-negative breast cancer (TNBC) status in relation to estrogen receptor-positive (ER)/HER2 status (referent) for reproductive risk factors.

Results: Relative to women who had ER/HER2 tumors, women who were age 19-24 years at first birth (OR, 1.78; 95% CI, 1.22-2.59) were more likely to have TNBC. Parous women were less likely to be diagnosed with HER2 breast cancer and more likely to be diagnosed with TNBC relative to ER/HER2 breast cancer. Postmenopausal parous women who breastfed were less likely to have TNBC [OR, 0.65 (95% CI, 0.43-0.99)].

Conclusions: This large pooled study of Black women with breast cancer revealed etiologic heterogeneity among breast cancer subtypes.

Impact: Black parous women who do not breastfeed are more likely to be diagnosed with TNBC, which has a worse prognosis, than with ER/HER2 breast cancer.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1158/1055-9965.EPI-20-1784DOI Listing
May 2021

Red meat consumption, cooking mutagens, NAT1/2 genotypes and pancreatic cancer risk in two ethnically diverse prospective cohorts.

Int J Cancer 2021 Apr 12. Epub 2021 Apr 12.

Department of Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles, California, USA.

There is limited evidence on the association between red meat consumption and pancreatic cancer among ethnic minorities. We assessed this relationship in two large prospective cohorts: the Multiethnic Cohort Study (MEC) and the Southern Community Cohort Study (SCCS). Demographic, dietary and other risk factor data were collected at cohort entry. Red meat intake was assessed using cohort-specific validated food frequency questionnaires. Incident pancreatic cancer cases were identified via linkages to state cancer registries. Cox regression was used to calculate relative risks (RRs) and 95% confidence intervals (CIs) for the association of red meat intake with pancreatic cancer risk in each cohort. We performed additional analyses to evaluate cooking methods, mutagens and effect modification by NAT1/2 genotypes. From a total of 184 542 (MEC) and 66 793 (SCCS) at-risk participants, we identified 1618 (MEC) and 266 (SCCS) incident pancreatic cancer cases. Red meat consumption was associated with pancreatic cancer risk in the MEC (RR 1.18, 95% CI 1.02-1.37) and with borderline statistical significance in the SCCS (RR 1.31, 95% CI 0.93-1.86). This association was significant in African Americans (RR 1.49, 95% CI 1.06-2.11) and Latinos (RR 1.44, 95% CI 1.02-2.04) in the MEC, and among African Americans (RR 1.55, 95% CI 1.03-2.33) in the SCCS. NAT2 genotypes appeared to modify the relationship between red meat and pancreatic cancer in the MEC (p = 0.03). Our findings suggest that the associations for red meat may be strongest in African Americans and Latinos. The mechanisms underlying the increased risk for these populations should be further investigated.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/ijc.33598DOI Listing
April 2021

Prediagnostic Antibody Responses to Proteins Are Not Associated with Risk of Colorectal Cancer in a Large U.S. Consortium.

Cancer Epidemiol Biomarkers Prev 2021 Jun 18;30(6):1279-1282. Epub 2021 Mar 18.

Clinical and Translational Epidemiology Unit, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts.

Background: The association between prediagnostic antibody responses to () and subsequent risk of colorectal cancer is not established.

Methods: We conducted a nested case-control study of 8,126 participants in a consortium of 10 prospective cohorts in the United States.

Results: Higher seroprevalence of any antibody was observed among non-White participants (51.1%) compared with White participants (31.2%). We did not find any statistically significant association between seropositivity to any of the eight proteins and colorectal cancer risk.

Conclusions: Prediagnostic antibody responses to proteins were not associated with the risk of colorectal cancer.

Impact: Future studies may consider a more specific detection of the immunoglobulin isotypes or focus on examining in stool or tissue samples.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1158/1055-9965.EPI-20-1471DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8172443PMC
June 2021

Discovery and fine-mapping of height loci via high-density imputation of GWASs in individuals of African ancestry.

Am J Hum Genet 2021 04 12;108(4):564-582. Epub 2021 Mar 12.

The Charles R. Bronfman Institute for Personalized Medicine, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.

Although many loci have been associated with height in European ancestry populations, very few have been identified in African ancestry individuals. Furthermore, many of the known loci have yet to be generalized to and fine-mapped within a large-scale African ancestry sample. We performed sex-combined and sex-stratified meta-analyses in up to 52,764 individuals with height and genome-wide genotyping data from the African Ancestry Anthropometry Genetics Consortium (AAAGC). We additionally combined our African ancestry meta-analysis results with published European genome-wide association study (GWAS) data. In the African ancestry analyses, we identified three novel loci (SLC4A3, NCOA2, ECD/FAM149B1) in sex-combined results and two loci (CRB1, KLF6) in women only. In the African plus European sex-combined GWAS, we identified an additional three novel loci (RCCD1, G6PC3, CEP95) which were equally driven by AAAGC and European results. Among 39 genome-wide significant signals at known loci, conditioning index SNPs from European studies identified 20 secondary signals. Two of the 20 new secondary signals and none of the 8 novel loci had minor allele frequencies (MAF) < 5%. Of 802 known European height signals, 643 displayed directionally consistent associations with height, of which 205 were nominally significant (p < 0.05) in the African ancestry sex-combined sample. Furthermore, 148 of 241 loci contained ≤20 variants in the credible sets that jointly account for 99% of the posterior probability of driving the associations. In summary, trans-ethnic meta-analyses revealed novel signals and further improved fine-mapping of putative causal variants in loci shared between African and European ancestry populations.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.ajhg.2021.02.011DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8059339PMC
April 2021

Polygenic hazard score is associated with prostate cancer in multi-ethnic populations.

Nat Commun 2021 02 23;12(1):1236. Epub 2021 Feb 23.

Division of Cancer Sciences, University of Manchester, Manchester Academic Health Science Centre, Radiotherapy Related Research, The Christie Hospital NHS Foundation Trust, Manchester, UK.

Genetic models for cancer have been evaluated using almost exclusively European data, which could exacerbate health disparities. A polygenic hazard score (PHS) is associated with age at prostate cancer diagnosis and improves screening accuracy in Europeans. Here, we evaluate performance of PHS (PHS, adapted for OncoArray) in a multi-ethnic dataset of 80,491 men (49,916 cases, 30,575 controls). PHS is associated with age at diagnosis of any and aggressive (Gleason score ≥ 7, stage T3-T4, PSA ≥ 10 ng/mL, or nodal/distant metastasis) cancer and prostate-cancer-specific death. Associations with cancer are significant within European (n = 71,856), Asian (n = 2,382), and African (n = 6,253) genetic ancestries (p < 10). Comparing the 80/20 PHS percentiles, hazard ratios for prostate cancer, aggressive cancer, and prostate-cancer-specific death are 5.32, 5.88, and 5.68, respectively. Within European, Asian, and African ancestries, hazard ratios for prostate cancer are: 5.54, 4.49, and 2.54, respectively. PHS risk-stratifies men for any, aggressive, and fatal prostate cancer in a multi-ethnic dataset.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41467-021-21287-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7902617PMC
February 2021

Prospective study of plasma levels of coenzyme Q10 and lung cancer risk in a low-income population in the Southeastern United States.

Cancer Med 2021 02 6;10(4):1439-1447. Epub 2021 Feb 6.

Division of Epidemiology, Department of Medicine, Vanderbilt Epidemiology Center, Vanderbilt-Ingram Cancer Center, Vanderbilt University School of Medicine, Nashville, TN, USA.

Background: Coenzyme Q10 (CoQ10) is a ubiquitous molecule in living organisms serving as a cofactor in energy production. Epidemiological studies have reported low CoQ10 levels being associated with an increased risk of various cancers. We conducted the first study to evaluate the association of CoQ10 concentrations with lung cancer risk.

Methods: A nested case-control study including 201 lung cancer cases and 395 matched controls from the Southern Community Cohort Study was conducted. Plasma CoQ10 levels were measured using high-performance liquid chromatography with photo-diode array detection. Conditional logistic regression models were applied to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for the association between plasma CoQ10 levels and lung cancer risk.

Results: Plasma CoQ10 concentration was inversely associated with the risk of lung cancer. After adjusting for age, sex, race, and socioeconomic status, the OR (95% CI) comparing the third to first tertile was 0.57 (0.36-0.91, P for trend = 0.02). Further adjustments for smoking, alcohol, chronic obstructive pulmonary disease, and body mass index attenuated the point estimate slightly (OR = 0.60, 95% CI = 0.34-1.08, P for trend = 0.11), comparing third to first tertiles. Stratified analyses identified a significant inverse association between plasma CoQ10 levels and lung cancer risk in current smokers, but not in former/never smokers. The association was more evident in cases who were diagnosed within 1 year of blood draw than in cases diagnosed after 1 year.

Conclusions: Low plasma CoQ10 was significantly associated with increased lung cancer risk, particularly among current smokers. The stronger association seen shortly following the blood draw suggests that CoQ10 may be related to disease progression.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/cam4.3637DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7926017PMC
February 2021

Religion, Spirituality, and Risk of End-Stage Kidney Disease Among Adults of Low Socioeconomic Status in the Southeastern United States.

J Health Care Poor Underserved 2020 ;31(4):1727-1746

Background: Religiosity, encompassing spirituality and religious practices, is associated with reduced disease incidence among individuals of low socioeconomic status and who self-identify as Black. We hypothesized that religiosity associates with reduced end-stage kidney disease (ESKD) risk among Black but not White adults of low socioeconomic status.

Design: Cox models of religiosity and ESKD risk in 76,443 adults.

Results: Black adults reporting high spirituality had reduced ESKD risk after adjusting for demographic characteristics [Hazard Ratio (HR) .82 (95% Confidence Interval (CI)) (.69-.98)], depressive symptoms, social support, and tobacco use [HR .81 (CI .68-.96)]. When clinical covariates were added, associations between spirituality and ESKD were slightly attenuated and lost significance [HR .85 (CI .68-1.06)]. Associations were not demonstrated among White adults.

Conclusions: Spirituality associates with reduced ESKD risk among Black adults of low socioeconomic status independent of demographic, psychosocial, and behavioral characteristics. Effect modification by race was not statistically significant.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1353/hpu.2020.0129DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7874531PMC
January 2020

Trans-ancestry genome-wide association meta-analysis of prostate cancer identifies new susceptibility loci and informs genetic risk prediction.

Nat Genet 2021 01 4;53(1):65-75. Epub 2021 Jan 4.

Cancer Epidemiology Division, Cancer Council Victoria, Melbourne, Victoria, Australia.

Prostate cancer is a highly heritable disease with large disparities in incidence rates across ancestry populations. We conducted a multiancestry meta-analysis of prostate cancer genome-wide association studies (107,247 cases and 127,006 controls) and identified 86 new genetic risk variants independently associated with prostate cancer risk, bringing the total to 269 known risk variants. The top genetic risk score (GRS) decile was associated with odds ratios that ranged from 5.06 (95% confidence interval (CI), 4.84-5.29) for men of European ancestry to 3.74 (95% CI, 3.36-4.17) for men of African ancestry. Men of African ancestry were estimated to have a mean GRS that was 2.18-times higher (95% CI, 2.14-2.22), and men of East Asian ancestry 0.73-times lower (95% CI, 0.71-0.76), than men of European ancestry. These findings support the role of germline variation contributing to population differences in prostate cancer risk, with the GRS offering an approach for personalized risk prediction.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41588-020-00748-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8148035PMC
January 2021

Associations of coffee and tea consumption with lung cancer risk.

Int J Cancer 2020 Dec 16. Epub 2020 Dec 16.

Department of Food and Nutrition, College of Human Ecology, Seoul National University, Seoul, South Korea.

Associations of coffee and tea consumption with lung cancer risk have been inconsistent, and most lung cancer cases investigated were smokers. Included in this study were over 1.1 million participants from 17 prospective cohorts. Cox regression analyses were conducted to estimate hazard ratios (HRs) and 95% confidence intervals (CIs). Potential effect modifications by sex, smoking, race, cancer subtype and coffee type were assessed. After a median 8.6 years of follow-up, 20 280 incident lung cancer cases were identified. Compared with noncoffee and nontea consumption, HRs (95% CIs) associated with exclusive coffee drinkers (≥2 cups/d) among current, former and never smokers were 1.30 (1.15-1.47), 1.49 (1.27-1.74) and 1.35 (1.15-1.58), respectively. Corresponding HRs for exclusive tea drinkers (≥2 cups/d) were 1.16 (1.02-1.32), 1.10 (0.92-1.32) and 1.37 (1.17-1.61). In general, the coffee and tea associations did not differ significantly by sex, race or histologic subtype. Our findings suggest that higher consumption of coffee or tea is associated with increased lung cancer risk. However, these findings should not be assumed to be causal because of the likelihood of residual confounding by smoking, including passive smoking, and change of coffee and tea consumption after study enrolment.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/ijc.33445DOI Listing
December 2020

Diabetes and liver cancer risk: A stronger effect in Whites than Blacks?

J Diabetes Complications 2021 Mar 1;35(3):107816. Epub 2020 Dec 1.

Division of Epidemiology, Vanderbilt University Medical Center, Nashville, TN, United States of America.

Background: Both diabetes and liver cancer are overrepresented among African Americans, but limited information is available on the interrelationship of these two diseases among African Americans. We examined the association of diabetes with the incidence of liver cancer and whether this varied by participant self-reported race/ethnicity.

Methods: Using the Southern Community Cohort Study, we conducted a cancer follow up (2002-2016) of a cohort of mostly low-income participants aged 40-79 with diabetes (n = 15,879) and without diabetes (n = 59,077) at study baseline. Cox regression was used to compute Hazard Ratios (HR) and 95% CIs for the risk of incident liver cancer.

Results: With 790,132 person years of follow up, 320 incident cases of liver cancer were identified. In analyses controlling for age, sex, race, BMI, current and former smoking, total alcohol consumption, family history of liver cancer, any hepatitis infection, hyperlipidemia and socioeconomic factors, the association between diabetes and risk of liver cancer differed significantly (p = 0.0001) between participants identifying as Black/African American (AA) or White/European American (EA). Diabetes was associated with 5.3-fold increased cancer risk among EAs (HR 5.4, 95% CI 3.2-9.3) vs an 80% increase (HR 1.8, 95% CI 1.3-2.5) among AAs. Furthermore, controlling for diabetes greatly attenuated the higher risk of liver cancer among AAs; indeed, while the cancer risk among those without diabetes was twice as high among AAs than EAs (HR = 2.0, 95% CI = 1.4-2.9), no excess in AAs was observed among those with diabetes (HR = 0.7, 95% CI = 0.4-1.1).

Conclusion: While liver cancer risk in general is greater in AAs than EAs and diabetes increases this risk in both racial/ethnic groups, diabetes appears to impact liver cancer to a much greater extent among EAs. The findings raise the possibility of racially different mechanisms and impacts of diabetes on this often fatal cancer among AAs and EAs.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jdiacomp.2020.107816DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8045414PMC
March 2021

Aspirin Use and Prostate Cancer among African-American Men in the Southern Community Cohort Study.

Cancer Epidemiol Biomarkers Prev 2021 Mar 8;30(3):539-544. Epub 2020 Dec 8.

Laboratory of Human Carcinogenesis, Center for Cancer Research, NCI, NIH, Bethesda, Maryland.

Background: The association of aspirin use with prostate cancer has been investigated, but few studies included African-American men. Here, we analyzed the relationship of aspirin intake with prostate cancer risk and mortality among African-American men in the Southern Community Cohort Study (SCCS).

Methods: SCCS recruited 22,426 African-American men between 2002 and 2009. Aspirin use was assessed at enrollment. Our exposures of interest were any aspirin use (regular strength, low-dose or baby aspirin, or half tablets of aspirin) and regular strength aspirin. Each exposure variable was compared with nonusers. Associations between aspirin use and prostate cancer risk and mortality were examined with Cox proportional hazards models.

Results: At enrollment, 5,486 men (25.1%) reported taking any aspirin and 2,634 men (12.1%) reported regular strength aspirin use. During follow-up (median, 13 years), 1,058 men developed prostate cancer, including 103 prostate cancer-specific deaths. Aspirin use was not associated with prostate cancer development [adjusted HR, 1.07; 95% confidence interval (CI), 0.92-1.25 for any aspirin use and HR, 0.97; 95% CI, 0.78-1.19 for regular strength aspirin], but was suggestively associated with reduced prostate cancer mortality (HR, 0.66; 95% CI, 0.39-1.14 for any aspirin use and HR, 0.41; 95% CI, 0.17-1.00 for regular strength aspirin).

Conclusions: Aspirin use at enrollment was tentatively associated with reduced prostate cancer mortality, but not risk, among African-American men in SCCS.

Impact: Prospective SCCS data suggest that aspirin use may help prevent lethal prostate cancer among this high-risk group of men.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1158/1055-9965.EPI-19-0792DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8049943PMC
March 2021

Association between lincRNA expression and overall survival for patients with triple-negative breast cancer.

Breast Cancer Res Treat 2021 Apr 27;186(3):769-777. Epub 2020 Nov 27.

Division of Epidemiology, Department of Medicine, Vanderbilt Epidemiology Center, Vanderbilt-Ingram Cancer Center, Vanderbilt University Medical Center, 2525 West End Avenue, Suite 800, Nashville, TN, 37203, USA.

Purpose: Long intergenic non-coding RNAs (lincRNAs) are increasingly recognized as important regulators for pathogenesis and/or prognosis of breast cancer, including triple-negative breast cancer (TNBC) subtype. However, few previous studies used RNA-sequencing (RNA-Seq) technology, and none included an independent replication.

Methods: To systematically evaluate the association between expression of lincRNAs and TNBC survival, we examined lincRNA expression profiles in TNBC tissues using RNA-Seq data for 200 TNBC patients from the Shanghai Breast Cancer Survival Study (SBCSS) and Southern Community Cohort Study (SCCS).

Results: Twenty-five lincRNAs were found to be associated with overall survival (P < 0.05 and no significant heterogeneity across studies at Q statistic P > 0.1), and 61 lincRNAs were associated with disease-free survival (DFS). Among these, two lincRNAs (LINC01270 and LINC00449) were significantly associated with both worse overall survival and DFS and were expressed at significantly higher levels in tumor tissues compared with adjacent normal breast tissues (log[Fold Change] > 0.5 and FDR < 0.05). We further evaluated the potential functions of LINC01270 and LINC00449 using in vitro functional experiments and found that siRNA-mediated knockdown of LINC01270 and LINC00449 expression significantly decreased cell viability, colony formation and cell migration ability in TNBC cells (P < 0.05).

Conclusions: Evidence from observational studies and in vitro experiments indicates that LINC00449 and LINC01270 may be prognostic biomarkers for TNBC.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s10549-020-06021-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8088339PMC
April 2021

Association of Combined Sero-Positivity to and with Risk of Colorectal Cancer.

Microorganisms 2020 Oct 30;8(11). Epub 2020 Oct 30.

Infections and Cancer Epidemiology, German Cancer Research Center (DKFZ), 69120 Heidelberg, Germany.

Previously, we found that risk of colorectal cancer (CRC) is increased in individuals with serum antibody response to both (HP) Vacuolating Cytotoxin (VacA) toxin or (SGG) pilus protein Gallo2178. In the present analysis, we tested the hypothesis that combined seropositivity to both antigens is a better indicator of CRC risk than seropositivity to single antigens. We used multiplex serologic assays to analyze pre-diagnostic serum for antibody responses from 4063 incident CRC cases and 4063 matched controls from 10 US cohorts. To examine whether combined SGG Gallo2178 and HP VacA sero-status was associated with CRC risk, we used conditional logistic regression models to estimate odds ratios (ORs) and 95% confidence intervals (CIs). Compared to dual sero-negative individuals, there was no increased risk for individuals sero-positive to SGG Gallo2178 only (OR: 0.93; 95% CI: 0.66-1.31) or to HP VacA only (OR: 1.08; 95% CI: 0.98-1.19). However, dual sero-positive individuals had a >50% increased odds of developing CRC (OR: 1.54; 95% CI: 1.16-2.04), suggesting an interaction between antibody responses to these two pathogens and CRC risk (p = 0.06). In conclusion, this study suggests that dual sero-positivity to HP VacA and SGG Gallo2178 is an indicator of increased risk of CRC.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/microorganisms8111698DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7693002PMC
October 2020

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

Sci Rep 2020 10 21;10(1):17907. Epub 2020 Oct 21.

Division of Epidemiology, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, USA.

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.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41598-020-72993-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7578784PMC
October 2020

Patterns and correlates of sleep duration in the Southern cohort community study.

Sleep Med 2020 11 10;75:459-467. Epub 2020 Sep 10.

Division of Gastroenterology, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, USA. Electronic address:

Objective: To investigate whether race (African American (AA) and white) is associated with sleep duration among adults from low socioeconomic (SES) strata and whether SES status, lifestyle behaviors, or health conditions are associated with sleep duration within race-sex groups.

Methods: This cross-sectional study includes 78,549 participants from the Southern Community Cohort Study (SCCS). Averaged daily sleep duration was assessed by weighted averages of self-reported sleep duration on weekdays and weekends. Adjusted odds ratios (ORs) of very short (<5 h/day), short (5-6 h/day), and long sleep (≥9 h/day) associated with pre-selected risk factors in each race-sex group were determined by multinomial logistic models.

Results: The prevalence of very short and short sleep was similar among AAs (6.2% and 29.1%) and whites (6.5% and 29.1%). Long sleep was considerably more prevalent among AAs (19.3%) than whites (13.0%). Very short sleep was associated with lower education and family income, with stronger associations among whites. Higher physical activity levels significantly decreased odds for both very short (OR = 0.80) and long sleep (OR = 0.78). Smoking, alcohol use, and dietary intake were not associated with sleep duration. Regardless of race or sex, very short, short, and long sleep were significantly associated with self-reported health conditions, especially depression (ORs were 2.06, 1.33, and 1.38, respectively).

Conclusions: Sleep duration patterns differed between AAs and whites from the underrepresented SCCS population with low SES. Sleep duration was associated with several socioeconomic, health behaviors, and health conditions depending on race and sex.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.sleep.2020.09.004DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7669688PMC
November 2020

Auto-antibodies to p53 and the Subsequent Development of Colorectal Cancer in a U.S. Prospective Cohort Consortium.

Cancer Epidemiol Biomarkers Prev 2020 12 24;29(12):2729-2734. Epub 2020 Sep 24.

Cancer Control and Population Sciences Program, Duke Cancer Institute, and Department of Population Health Sciences, Duke University, Durham, North Carolina.

Background: Auto-antibodies to tumor suppressor p53 are found in a subset of patients with colorectal cancer. A recent prospective study in the United States has reported a significant 1.8-fold increased odds for colorectal cancer development with prediagnostic seropositivity to p53. In this study, we sought to examine this association in a U.S. colorectal cancer cohort consortium to evaluate the potential utility of p53 auto-antibodies as an early biomarker for colorectal cancer.

Methods: Auto-antibodies to p53 were measured in prediagnostic blood samples of 3,702 incident colorectal cancer cases and 3,702 controls, matched by age, race, and sex, from 9 U.S. prospective cohorts. The association of seropositivity to p53 with colorectal cancer risk, overall and by time between blood draw and diagnosis, was determined by conditional logistic regression.

Results: Overall, 5% of controls and 7% of cases were seropositive to p53, resulting in a statistically significant 33% increased colorectal cancer risk [odds ratio (OR), 1.33; 95% confidence interval (CI), 1.09-1.61]. By follow-up time, the association was only significant with colorectal cancer diagnoses within 4 years after blood draw (OR, 2.27; 95% CI, 1.62-3.19), but not thereafter (OR, 0.97; 95% CI, 0.76-1.24).

Conclusions: In this large consortium of prospective cohorts, we found that prediagnostic seropositivity to tumor suppressor p53 was significantly associated with an over 2-fold increased odds of developing colorectal cancer within 4 years after blood draw.

Impact: Our finding suggests that p53 seropositivity may not be a useful predictor of long-term colorectal cancer risk; however, it might be considered as a marker to aid in the early diagnosis of colorectal cancer.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1158/1055-9965.EPI-20-0780DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7710535PMC
December 2020

Replication and Genetic Risk Score Analysis for Pancreatic Cancer in a Diverse Multiethnic Population.

Cancer Epidemiol Biomarkers Prev 2020 12 21;29(12):2686-2692. Epub 2020 Sep 21.

Department of Preventive Medicine, Keck School of Medicine of University of Southern California, Los Angeles, California.

Background: Genome-wide association studies (GWAS) have identified several SNPs associated with pancreatic cancer. No studies yet have attempted to replicate these SNPs in US minority populations. We aimed to replicate the associations of 31 GWAS-identified SNPs with pancreatic cancer and build and test a polygenic risk score (PRS) for pancreatic cancer in an ethnically diverse population.

Methods: We evaluated 31 risk variants in the Multiethnic Cohort and the Southern Community Cohort Study. We included 691 pancreatic ductal adenocarcinoma (PDAC) cases and 13,778 controls from African-American, Japanese-American, Latino, Native Hawaiian, and white participants. We tested the association between each SNP and PDAC, established a PRS using the 31 SNPs, and tested the association between the score and PDAC risk.

Results: Eleven of the 31 SNPs were replicated in the multiethnic sample. The PRS was associated with PDAC risk [OR top vs. middle quintile = 2.25 (95% confidence interval, 1.73-2.92)]. Notably, the PRS was associated with PDAC risk in all ethnic groups except Native Hawaiian (OR per risk allele ranged from 1.33 in Native Hawaiians to 1.91 in African Americans; heterogeneity = 0.12).

Conclusions: This is the first study to replicate 11 of the 31 GWAS-identified risk variants for pancreatic cancer in multiethnic populations, including African Americans, Japanese Americans, and Latinos. Our results also suggest a potential utility of PRS with GWAS-identified risk variants for the identification of individuals at increased risk for PDAC across multiple ethnic groups.

Impact: PRS can potentially be used to stratify pancreatic cancer risk across multiple ethnic groups.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1158/1055-9965.EPI-20-0963DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7710597PMC
December 2020

African-specific improvement of a polygenic hazard score for age at diagnosis of prostate cancer.

Int J Cancer 2021 01 24;148(1):99-105. Epub 2020 Sep 24.

UMR Inserm 1134 Biologie Intégrée du Globule Rouge, INSERM/Université Paris Diderot-Université Sorbonne Paris Cité/INTS/Université des Antilles, Paris, France.

Polygenic hazard score (PHS) models are associated with age at diagnosis of prostate cancer. Our model developed in Europeans (PHS46) showed reduced performance in men with African genetic ancestry. We used a cross-validated search to identify single nucleotide polymorphisms (SNPs) that might improve performance in this population. Anonymized genotypic data were obtained from the PRACTICAL consortium for 6253 men with African genetic ancestry. Ten iterations of a 10-fold cross-validation search were conducted to select SNPs that would be included in the final PHS46+African model. The coefficients of PHS46+African were estimated in a Cox proportional hazards framework using age at diagnosis as the dependent variable and PHS46, and selected SNPs as predictors. The performance of PHS46 and PHS46+African was compared using the same cross-validated approach. Three SNPs (rs76229939, rs74421890 and rs5013678) were selected for inclusion in PHS46+African. All three SNPs are located on chromosome 8q24. PHS46+African showed substantial improvements in all performance metrics measured, including a 75% increase in the relative hazard of those in the upper 20% compared to the bottom 20% (2.47-4.34) and a 20% reduction in the relative hazard of those in the bottom 20% compared to the middle 40% (0.65-0.53). In conclusion, we identified three SNPs that substantially improved the association of PHS46 with age at diagnosis of prostate cancer in men with African genetic ancestry to levels comparable to Europeans.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/ijc.33282DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8135907PMC
January 2021

Investigating the associations of glycemic load and glycemic index with lung cancer risk in the Southern Community Cohort Study.

Cancer Causes Control 2020 Dec 11;31(12):1069-1077. Epub 2020 Sep 11.

Division of Epidemiology, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, USA.

Purpose: Diets with a high glycemic load (GL) or glycemic index (GI) may increase cancer risk. Findings from prior studies on the relationship between GL, GI, and lung cancer risk are inconsistent. We investigated this relationship in a large prospective cohort.

Methods: We analyzed data from the Southern Community Cohort Study, a prospective cohort that includes diverse racial groups predominantly low-income adults aged 40-79 in 12 southeastern states of the USA. We estimated dietary GL and GI values using data collected from food frequency questionnaires at baseline. Dietary GL and GI were energy adjusted by residual method and categorized into sex-specific quintiles. Cox proportional hazard regression was used to assess the associations between dietary GL, GI, and lung cancer risk. We further performed stratified analyses by various factors.

Results: Intakes of individual food items or food groups that commonly contribute to GL were similar between blacks and whites in the cohort. After excluding the first two years of follow-up, 947 incident lung cancers were ascertained among 55,068 participants. Neither dietary GL nor GI was significantly associated with incident lung cancer risk in the overall population (GL: Q5 vs. Q1, HR = 0.88, 95% CI 0.72-1.07, p = 0.29; GI: Q5 vs. Q1, HR = 1.06, 95% CI 0.86-1.30, p = 0.71), nor in subgroups of populations (p > 0.05), in multivariable-adjusted analyses.

Conclusion: Dietary GL and GI were not independently associated with incident lung cancer risk in a large understudied population.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s10552-020-01344-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7572706PMC
December 2020

Racial Differences in CagA Sero-prevalence in a Consortium of Adult Cohorts in the United States.

Cancer Epidemiol Biomarkers Prev 2020 10 20;29(10):2084-2092. Epub 2020 Aug 20.

Cancer Control and Population Health Sciences Program, Duke Cancer Institute, Durham, North Carolina.

Background: Prevalence of () infection, the main risk factor for gastric cancer, has been decreasing in the United States; however, there remains a substantial racial disparity. Moreover, the time-trends for prevalence of CagA-positive infection, the most virulent form, are unknown in the U.S.

Population: We sought to assess prevalence of CagA-positive infection over time by race in the United States.

Methods: We utilized multiplex serology to quantify antibody responses to antigens in 4,476 participants across five cohorts that sampled adults from 1985 to 2009. Using log-binomial regression models, we calculated prevalence ratios and 95% confidence intervals for the association between -CagA sero-prevalence and birth year by race.

Results: African Americans were three times more likely to be -CagA sero-positive than Whites. After adjustment, -CagA sero-prevalence was lower with increasing birth year among Whites ( = 0.001), but remained stable for African Americans. When stratified by sex and education separately, the decline in -CagA sero-positivity among Whites remained only for females ( < 0.001) and was independent of educational attainment. Among African Americans, there was no difference by sex; furthermore, sero-prevalence increased with increasing birth year among those with a high school education or less ( = 0.006).

Conclusions: Among individuals in the United States born from the 1920s to 1960s, -CagA sero-prevalence has declined among Whites, but not among African Americans.

Impact: Our findings suggest a widening racial disparity in the prevalence of the most virulent form of , the main cause of gastric cancer.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1158/1055-9965.EPI-20-0525DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7584346PMC
October 2020

A Description of Risk Factors for Non-alcoholic Fatty Liver Disease in the Southern Community Cohort Study: A Nested Case-Control Study.

Front Nutr 2020 21;7:71. Epub 2020 May 21.

Vanderbilt Center for Kidney Disease, Vanderbilt University Medical Center, Nashville, TN, United States.

Non-alcoholic fatty liver disease (NAFLD) is associated with obesity and hypercholesterolemia. In addition, total fat and folate intake have been associated with NAFLD. We investigated risk factors for NAFLD among individuals of largely low socioeconomic status, and whether these associations differed by race. A nested case-control study was conducted within the Southern Community Cohort Study. Through linkage of the cohort with Centers for Medicare and Medicaid Services, International Classification of Diseases, Ninth Revision, Clinical Modification codes were used to identify incident NAFLD cases. Controls were matched 4:1 to cases on enrollment age, sex, and race. A logistic regression was used to estimate odds ratios for the associations of NAFLD with covariates of interest. Neither total fat nor folate intake was significantly associated with NAFLD. Hypercholesterolemia (odds ratio 1.21) and body mass index (75th vs. 25th percentile) for blacks (odds ratio 1.96) and whites (odds ratio 2.33) were associated with an increased risk of non-alcoholic fatty liver disease. No significant interaction with race for any of the studied variables was noted. Both hypercholesterolemia and increasing body mass index, but not total fat and folate intake, were risk factors for NAFLD in the Southern Community Cohort Study.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fnut.2020.00071DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7326146PMC
May 2020

A Germline Variant at 8q24 Contributes to Familial Clustering of Prostate Cancer in Men of African Ancestry.

Eur Urol 2020 09 12;78(3):316-320. Epub 2020 May 12.

Department of Surgery, Center for Prostate Disease Research, Uniformed Services University of the Health Sciences, Bethesda, MD, USA.

Although men of African ancestry have a high risk of prostate cancer (PCa), no genes or mutations have been identified that contribute to familial clustering of PCa in this population. We investigated whether the African ancestry-specific PCa risk variant at 8q24, rs72725854, is enriched in men with a PCa family history in 9052 cases, 143 cases from high-risk families, and 8595 controls of African ancestry. We found the risk allele to be significantly associated with earlier age at diagnosis, more aggressive disease, and enriched in men with a PCa family history (32% of high-risk familial cases carried the variant vs 23% of cases without a family history and 12% of controls). For cases with two or more first-degree relatives with PCa who had at least one family member diagnosed at age <60 yr, the odds ratios for TA heterozygotes and TT homozygotes were 3.92 (95% confidence interval [CI] = 2.13-7.22) and 33.41 (95% CI = 10.86-102.84), respectively. Among men with a PCa family history, the absolute risk by age 60 yr reached 21% (95% CI = 17-25%) for TA heterozygotes and 38% (95% CI = 13-65%) for TT homozygotes. We estimate that in men of African ancestry, rs72725854 accounts for 32% of the total familial risk explained by all known PCa risk variants. PATIENT SUMMARY: We found that rs72725854, an African ancestry-specific risk variant, is more common in men with a family history of prostate cancer and in those diagnosed with prostate cancer at younger ages. Men of African ancestry may benefit from the knowledge of their carrier status for this genetic risk variant to guide decisions about prostate cancer screening.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.eururo.2020.04.060DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7805560PMC
September 2020

Differences in antibody levels to H. pylori virulence factors VacA and CagA among African Americans and whites in the Southeast USA.

Cancer Causes Control 2020 Jun 28;31(6):601-606. Epub 2020 Mar 28.

Cancer Control and Population Health Sciences Program, Duke Cancer Institute and Department of Population Health Sciences, Duke University, Durham, NC, USA.

Purpose: Helicobacter pylori (H. pylori) is the leading cause of gastric cancer. High antibody levels to H. pylori virulence factors Vacuolating cytotoxin A (VacA) and Cytotoxin-associated gene A (CagA) have been suggested as gastric cancer risk markers. In the USA, H. pylori sero-prevalence is twofold higher in African Americans compared to whites. We sought to assess whether African Americans also exhibit higher antibody levels to VacA and CagA.

Methods: Antibody responses to H. pylori proteins were measured by multiplex serology in 686 African Americans and whites of the Southern Community Cohort Study. Among VacA- and CagA-seropositives, we analyzed the association of race with antibody level using logistic regression models to produce odds ratios (OR) and 95% confidence intervals (CI).

Results: Sero-positive African Americans had significantly higher mean antibody levels to both VacA and CagA, which resulted in increased odds for the highest quartile of antibody levels compared to sero-positive whites (VacA, OR: 6.08; 95% CI 3.41, 10.86; CagA, OR: 3.77; 95% CI 1.61, 8.84).

Conclusion: Our findings support future studies to assess the association of differential antibody responses by race with risk of gastric cancer in the USA, which could then aid in developing targeted H. pylori eradication strategies.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s10552-020-01295-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7286423PMC
June 2020

Reply to Kenyon, "Are Differences in the Oral Microbiome Due to Ancestry or Socioeconomics?"

mSystems 2020 Mar 10;5(2). Epub 2020 Mar 10.

Division of Epidemiology, Department of Medicine, Vanderbilt Epidemiology Center, Vanderbilt-Ingram Cancer Center, Vanderbilt University Medical Center, Nashville, Tennessee, USA

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1128/mSystems.00891-19DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7065519PMC
March 2020

Lymphedema Signs, Symptoms, and Diagnosis in Women Who Are in Minority and Low-Income Groups and Have Survived Breast Cancer.

Phys Ther 2020 03;100(3):487-499

International Epidemiology Institute, Rockville, Maryland; and Vanderbilt-Ingram Cancer Center, Vanderbilt University Medical Center, Nashville, Tennessee.

Background: Breast cancer-related lymphedema (BCRL) is a well-known side effect of cancer and its treatment with wide-ranging prevalence estimates.

Objective: This study describes associations between breast cancer-related lymphedema (BCRL) signs, symptoms, and diagnosis for women who were African American, white, or had a low income and survived breast cancer.

Design: This is a cross-sectional, observational study that used a computer-assisted telephone interview.

Methods: Women who had survived breast cancer were queried on the presence of 5 lymphedema signs and symptoms (edema in the breast, axilla, arm, and/or hand; tissue fibrosis; pitting; hemosiderin staining; heaviness) and whether they had a diagnosis of BCRL. Relationships between signs/symptoms and diagnosis for each group were evaluated with kappa and chi-square statistics.

Results: The study sample included 528 women who had survived breast cancer (266 white and 262 African American), with 514 reporting complete data on household income; 45% of the latter reported an annual household income of ≤$20,000. Women who were African American or had a low income were nearly twice as likely as women who were white to have any of 8 signs/symptoms of BCRL. Regardless of race and income, >50% of women with all BCRL signs and symptoms reported that they were not diagnosed with BCRL.

Limitations: The main limitations of our study are the lack of medical chart data and longitudinal design.

Conclusions: Women who were African American or had a low income and had survived breast cancer had a greater burden of BCRL signs and symptoms than women who were white. The lack of a strong association between BCRL signs, symptoms, and diagnosis suggests that BCRL may be underdiagnosed. These findings suggest that more rigorous screening and detection of BCRL-especially for women who are African American or have a low income-may be warranted. Cancer rehabilitation programs may be able to fill this gap.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/ptj/pzaa002DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7246063PMC
March 2020

Race and Sex Differences in Modifiable Risk Factors and Incident Heart Failure.

JACC Heart Fail 2020 02 11;8(2):122-130. Epub 2019 Nov 11.

Vanderbilt Translational and Clinical Cardiovascular Research Center, Vanderbilt University Medical Center, Nashville, Tennessee; Division of Cardiovascular Medicine, Vanderbilt University Medical Center, Nashville, Tennessee. Electronic address:

Objectives: The purpose of this study was to examine race- and sex-based variation in the associations between modifiable risk factors and incident heart failure (HF) among the SCCS (Southern Community Cohort Study) participants.

Background: Low-income individuals in the southeastern United States have high HF incidence rates, but relative contributions of risk factors to HF are understudied in this population.

Methods: We studied 27,078 black or white SCCS participants (mean age: 56 years, 69% black, 63% women) enrolled between 2002 and 2009, without prevalent HF, receiving Centers for Medicare and Medicaid Services. The presence of hypertension, diabetes mellitus, physical underactivity, high body mass index, smoking, high cholesterol, and poor diet was assessed at enrollment. Incident HF was ascertained using International Classification of Diseases-9th revision, codes 428.x in Centers for Medicare and Medicaid Services data through December 31, 2010. Individual risk and population attributable risk for HF for each risk factor were quantified using multivariable Cox models.

Results: During a median (25th, 75th percentile) 5.2 (3.1, 6.7) years, 4,341 (16%) participants developed HF. Hypertension and diabetes were associated with greatest HF risk, whereas hypertension contributed the greatest population attributable risk, 31.8% (95% confidence interval: 27.3 to 36.0). In black participants, only hypertension and diabetes associated with HF risk; in white participants, smoking and high body mass index also associated with HF risk. Physical underactivity was a risk factor only in white women.

Conclusions: In this high-risk, low-income cohort, contributions of risk factors to HF varied, particularly by race. To reduce the population burden of HF, interventions tailored for specific race and sex groups may be warranted.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jchf.2019.11.001DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6995453PMC
February 2020

A meta-analysis of genome-wide association studies of multiple myeloma among men and women of African ancestry.

Blood Adv 2020 01;4(1):181-190

Division of Cancer Genetics and Epidemiology, National Cancer Institute, National Institutes of Health, Department of Health and Human Services, Bethesda, MD.

Persons of African ancestry (AA) have a twofold higher risk for multiple myeloma (MM) compared with persons of European ancestry (EA). Genome-wide association studies (GWASs) support a genetic contribution to MM etiology in individuals of EA. Little is known about genetic risk factors for MM in individuals of AA. We performed a meta-analysis of 2 GWASs of MM in 1813 cases and 8871 controls and conducted an admixture mapping scan to identify risk alleles. We fine-mapped the 23 known susceptibility loci to find markers that could better capture MM risk in individuals of AA and constructed a polygenic risk score (PRS) to assess the aggregated effect of known MM risk alleles. In GWAS meta-analysis, we identified 2 suggestive novel loci located at 9p24.3 and 9p13.1 at P < 1 × 10-6; however, no genome-wide significant association was noted. In admixture mapping, we observed a genome-wide significant inverse association between local AA at 2p24.1-23.1 and MM risk in AA individuals. Of the 23 known EA risk variants, 20 showed directional consistency, and 9 replicated at P < .05 in AA individuals. In 8 regions, we identified markers that better capture MM risk in persons with AA. AA individuals with a PRS in the top 10% had a 1.82-fold (95% confidence interval, 1.56-2.11) increased MM risk compared with those with average risk (25%-75%). The strongest functional association was between the risk allele for variant rs56219066 at 5q15 and lower ELL2 expression (P = 5.1 × 10-12). Our study shows that common genetic variation contributes to MM risk in individuals with AA.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1182/bloodadvances.2019000491DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6960456PMC
January 2020