Publications by authors named "William J Blot"

309 Publications

Dispositional optimism and optimistic bias: Associations with cessation motivation, confidence, and attitudes.

Health Psychol 2022 Jul 28. Epub 2022 Jul 28.

Department of Medicine.

Objective: To test whether 2 conceptually overlapping constructs, dispositional optimism (generalized positive expectations) and optimistic bias (inaccurately low risk perceptions), may have different implications for smoking treatment engagement.

Method: Predominantly Black, low-income Southern Community Cohort study smokers (n = 880) self-reported dispositional optimism and pessimism (Life Orientation Test-Revised subscales: 0 = neutral, 12 = high optimism/pessimism), comparative lung cancer risk (Low/Average/High), and information to calculate objective lung cancer risk (Low/Med/High). Perceived risk was categorized as accurate (perceived = objective), optimistically-biased (perceived < objective), or pessimistically-biased (perceived > objective). One-way ANOVAs tested associations between dispositional optimism/pessimism and perceived risk accuracy. Multivariable logistic regressions tested independent associations of optimism/pessimism and perceived risk accuracy with cessation motivation (Low/High), confidence (Low/High), and precision treatment attitudes (Favorable/Unfavorable), controlling for sociodemographics and nicotine dependence.

Results: Mean dispositional optimism/pessimism scores were 8.41 ( = 2.59) and 5.65 ( = 3.02), respectively. Perceived lung cancer risk was 38% accurate, 27% optimistically-biased, and 35% pessimistically-biased. Accuracy was unrelated to dispositional optimism ((2, 641) = 1.23, = .29), though optimistically-biased (vs. pessimistically-biased) smokers had higher dispositional pessimism ((2, 628) = 3.17, = .043). Dispositional optimism was associated with higher confidence (Adjusted odds ratio [A] = 1.71, 95% CI [1.42, 2.06], < .001) and favorable precision treatment attitudes (A = 1.66, 95% CI [1.37, 2.01], < .001). Optimistically-biased (vs. accurate) risk perception was associated with lower motivation (A = .64, 95% CI [.42, .98], = .041) and less favorable precision treatment attitudes (A = .59, 95% CI [.38, .94], = .029).

Conclusions: Dispositional optimism and lung cancer risk perception accuracy were unrelated. Dispositional optimism was associated with favorable engagement-related outcomes and optimistically-biased risk perception with unfavorable outcomes, reinforcing the distinctiveness of these constructs and their implications for smoking treatment. (PsycInfo Database Record (c) 2022 APA, all rights reserved).
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http://dx.doi.org/10.1037/hea0001184DOI Listing
July 2022

Associations of Pre-Diagnostic Serum Levels of Total Bilirubin and Albumin With Lung Cancer Risk: Results From the Southern Community Cohort Study.

Front Oncol 2022 23;12:895479. Epub 2022 Jun 23.

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

Background: Previous studies conducted among European and Asian decedents reported inverse associations of serum total bilirubin and albumin with lung cancer risk. Yet, no study has been conducted among African Americans or low-income European Americans.

Methods: This study included 522 incident lung cancer cases and 979 matched controls nested in the Southern Community Cohort Study, a cohort of predominantly low-income African and European Americans. Serum levels of total bilirubin and albumin, collected up to 11 years prior to case diagnoses, were measured by a clinical chemistry analyzer. Conditional logistic regression models were applied to evaluate the associations of total bilirubin and albumin with lung cancer risk.

Results: Overall, serum levels of total bilirubin (OR = 0.96, 95% CI: 0.66-1.39) were not significantly associated with lung cancer risk. However, higher levels of serum total bilirubin were significantly associated with decreased risk of lung cancer among participants who were diagnosed within two years following sample collection (OR = 0.36, 95% CI: 0.15-0.87) and among former/never smokers (OR = 0.54, 95% CI: 0.32-0.93). Serum levels of albumin were significantly associated with decreased risk of lung cancer overall (OR = 0.70, 95% CI: 0.50-0.98) and among African Americans (OR = 0.62, 95% CI: 0.41-0.96), but not among European Americans.

Conclusion: Our results indicate that in a low-income African American and European American population, serum levels of total bilirubin may be related to lung cancer progression and differ by smoking status. Meanwhile, the association of serum albumin levels with lung cancer risk may differ by race. Further studies are warranted to confirm these results.
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http://dx.doi.org/10.3389/fonc.2022.895479DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9261263PMC
June 2022

Absolute Risk of Oropharyngeal Cancer After an HPV16-E6 Serology Test and Potential Implications for Screening: Results From the Human Papillomavirus Cancer Cohort Consortium.

J Clin Oncol 2022 Jun 14:JCO2101785. Epub 2022 Jun 14.

Division of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville, MD.

Purpose: Seropositivity for the HPV16-E6 oncoprotein is a promising marker for early detection of oropharyngeal cancer (OPC), but the absolute risk of OPC after a positive or negative test is unknown.

Methods: We constructed an OPC risk prediction model that integrates (1) relative odds of OPC for HPV16-E6 serostatus and cigarette smoking from the human papillomavirus (HPV) Cancer Cohort Consortium (HPVC3), (2) US population risk factor data from the National Health Interview Survey, and (3) US sex-specific population rates of OPC and mortality.

Results: The nine HPVC3 cohorts included 365 participants with OPC with up to 10 years between blood draw and diagnosis and 5,794 controls. The estimated 10-year OPC risk for HPV16-E6 seropositive males at age 50 years was 17.4% (95% CI, 12.4 to 28.6) and at age 60 years was 27.1% (95% CI, 19.2 to 45.4). Corresponding 5-year risk estimates were 7.3% and 14.4%, respectively. For HPV16-E6 seropositive females, 10-year risk estimates were 3.6% (95% CI, 2.5 to 5.9) at age 50 years and 5.5% (95% CI, 3.8 to 9.2) at age 60 years and 5-year risk estimates were 1.5% and 2.7%, respectively. Over 30 years, after a seropositive result at age 50 years, an estimated 49.9% of males and 13.3% of females would develop OPC. By contrast, 10-year risks among HPV16-E6 seronegative people were very low, ranging from 0.01% to 0.25% depending on age, sex, and smoking status.

Conclusion: We estimate that a substantial proportion of HPV16-E6 seropositive individuals will develop OPC, with 10-year risks of 17%-27% for males and 4%-6% for females age 50-60 years in the United States. This high level of risk may warrant periodic, minimally invasive surveillance after a positive HPV16-E6 serology test, particularly for males in high-incidence regions. However, an appropriate clinical protocol for surveillance remains to be established.
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http://dx.doi.org/10.1200/JCO.21.01785DOI Listing
June 2022

Association of Healthy Lifestyles with Risk of Alzheimer Disease and Related Dementias in Low-Income Black and White Americans.

Neurology 2022 Jun 13. Epub 2022 Jun 13.

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

Objective: While the importance of healthy lifestyles for preventing Alzheimer's disease and related dementias (ADRD) has been recognized, epidemiologic evidence remains limited for non-White or low-income individuals who bear disproportionate burdens of ADRD. This population-based cohort study aims to investigate associations of lifestyle factors, individually and together, with the risk of ADRD among socioeconomically disadvantaged Americans.

Methods: In the Southern Community Cohort Study, comprising two-thirds self-reported Black and primarily low-income Americans, we identified incident ADRD using claims data among participants enrolled in Medicare for at least 12 consecutive months after age 65. Five lifestyle factors-tobacco smoking, alcohol consumption, leisure-time physical activity (LTPA), sleep hours, and diet quality- were each scored 0 (unhealthy), 1 (intermediate), or 2 (healthy) based on health guidelines. A composite lifestyle score was created by summing all scores. Cox regression was used to estimate hazard ratios (HRs, 95% CIs) for incident ADRD, treating death as a competing risk.

Results: We identified 1,694 patients with newly diagnosed ADRD among 17,209 participants during a median follow-up of 4.0 years in claims data; the mean age at ADRD diagnosis was 74.0 years. Healthy lifestyles were individually associated with 11%-25% reduced risk of ADRD: multivariable-adjusted HR (95% CI) was 0.87 (0.76-0.99) for never vs. current smoking, 0.81 (0.72-0.92) for low-to-moderate vs. no alcohol consumption, 0.89 (0.77-1.03) for ≥150 minutes of moderate or ≥75 minutes of vigorous LTPA each week vs. none, 0.75 (0.64-0.87) for 7-9 hours vs. >9 hours of sleep, and 0.85 (0.75-0.96) for the highest vs. lowest tertiles of Healthy Eating Index. The composite lifestyle score showed a dose-response association with up to 36% reduced risk of ADRD: multivariable-adjusted HRs (95% CIs) across quartiles were 1 (ref), 0.88 (0.77-0.99), 0.79 (0.70-0.90), and 0.64 (0.55-0.74); -trend<0.001. The beneficial associations were observed regardless of participants' sociodemographics (e.g., race, education, and income) and health conditions (e.g., history of cardiometabolic diseases and depression).

Conclusion: Our findings support significant benefits of healthy lifestyles for ADRD prevention among socioeconomically disadvantaged Americans, suggesting that promoting healthy lifestyles and reducing barriers to lifestyle changes are crucial to tackling the growing burden and disparities posed by ADRD.
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http://dx.doi.org/10.1212/WNL.0000000000200774DOI Listing
June 2022

Sociocultural Factors, Access to Healthcare, and Lifestyle: Multifactorial Indicators in Association with Colorectal Cancer Risk.

Cancer Prev Res (Phila) 2022 May 23. Epub 2022 May 23.

Vanderbilt University Medical Center, Nashville, TN, United States.

Black Americans of low SES have higher colorectal cancer (CRC) incidence than other groups in the US. However, much of the research that identifies CRC risk factors is conducted in cohorts of high SES and non-Hispanic white participants. Adults participants of the Southern Community Cohort Study (N=75,182) were followed for a median of 12.25 years where 742 incident CRCs were identified. The majority of the cohort are non-Hispanic white or Black and have low household income. Cox models were used to estimate hazard ratios (HRs) for CRC incidence associated with sociocultural factors, access to and use of healthcare, and healthy lifestyle scores to represent healthy eating, alcohol intake, smoking and physical activity. The association between Black race and CRC was consistent and not diminished by accounting for SES, access to healthcare or healthy lifestyle (HR=1.34; 95%CI:1.10,1.63). CRC screening was a strong, risk reduction factor for CRC (HR=0.65; 95%CI:0.55,0.78), and among CRC-screened, Black race was not associated with risk. Participants with >= high school education were at lower CRC risk (HR=0.81; 95%CI:0.67,0.98). Income and neighborhood-level SES were not strongly associated with CRC risk. Whereas individual health behaviors were not associated with risk, participants that reported adhering to >=3 health behaviors had a 19% (95%CI:1%,34%) decreased CRC risk compared to participants that reported =<1 behaviors. The association was consistent in fully-adjusted models, although HRs were no longer significant. CRC screening, education, and a lifestyle that includes healthy behaviors lowers CRC risk. Racial disparities in CRC risk may be diminished by CRC screening.
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http://dx.doi.org/10.1158/1940-6207.CAPR-22-0090DOI Listing
May 2022

Associations of lung cancer risk with biomarkers of Helicobacter pylori infection.

Carcinogenesis 2022 Jun;43(6):538-546

Division of Epidemiology, Department of Medicine, Vanderbilt Epidemiology Center, Vanderbilt-Ingram Cancer Center, Vanderbilt University School of Medicine, Nashville, TN 37203, USA.

Helicobacter pylori infection has been suggested to be associated with lung cancer risk. However, information is lacking on whether the association differs by H. pylori antigen. We conducted a nested case-control study within the Southern Community Cohort Study, including 295 incident lung cancer cases and 295 controls. Helicobacter pylori multiplex serology assay was performed to detect antibodies to 15 H. pylori proteins. Conditional logistic regression was used to estimate odds ratios (ORs) and confidence intervals (95% CIs) after adjustment for covariates. Overall H. pylori+ was associated with a non-statistically significant increased risk of lung cancer (OR: 1.29; 95% CI: 0.85-1.95). Significant associations, however, were observed for H. pylori+ VacA+ (OR: 1.64; 95% CI: 1.02-2.62) and H. pylori+ Catalase+ (OR: 1.75; 95% CI: 1.11-2.77). The positive association of H. pylori+ Catalase+ with lung cancer risk was predominantly seen among African Americans (OR: 2.09; 95% CI: 1.11-3.95) but not European Americans (OR: 1.20; 95% CI: 0.56-2.54). Among participants who smoked ≥ 30 pack-years, overall H. pylori+ (OR: 1.85; 95% CI: 1.02-3.35), H. pylori+ CagA+ (OR: 2.77; 95% CI: 1.35-5.70), H. pylori+ VacA+ (OR: 2.53; 95% CI: 1.25-5.13) and H. pylori+ HP1564+ (OR: 2.01; 95% CI: 1.07-3.77) were associated with increased risk of lung cancer. Our study provides novel evidence that associations of H. pylori infection with lung cancer risk differ by H. pylori biomarker, may be more evident among African Americans and may be modified by smoking habits. Furthermore, studies are warranted to confirm our findings.
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http://dx.doi.org/10.1093/carcin/bgac047DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9234758PMC
June 2022

Smoking Quit Rates Among Menthol vs Nonmenthol Smokers: Implications Regarding a US Ban on the Sale of Menthol Cigarettes.

J Natl Cancer Inst 2022 07;114(7):953-958

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

Background: A ban on the sale of menthol cigarettes in the United States is currently under consideration. A justification is that menthol cigarettes are harder to quit, particularly for African American smokers who use menthols much more frequently than White smokers, but epidemiologic data are limited.

Methods: In a cohort of 16 425 mostly low-income African American and White current cigarette smokers enrolled during 2002-2009, we computed smoking quit and reuptake rates at 3 follow-ups conducted means of 4.6, 7.7, and 11 years after entry. Generalized estimation equations were used to compute odds ratios (ORs) and 95% confidence intervals (CIs) for quitting and resuming smoking for menthol vs nonmenthol smokers adjusted for race, age, education, income, and smoking pack-years.

Results: Crude annual quit rates among current smokers were 4.3% for menthol and 4.5% for nonmenthol smokers, with adjusted odds ratios of quitting for menthol vs nonmenthol smokers of 1.01 (95% CI = 0.91 to 1.11) overall, 0.99 (95% CI = 0.87 to 1.12) among African American smokers, and 1.02 (95% CI = 0.88 to 1.20) among White smokers. Crude annual smoking reuptake rates were somewhat higher among menthol smokers (8.4%) than nonmenthol smokers (7.1%), with an adjusted odds ratio of 1.19 (95% CI = 0.97 to 1.47), but net quit rates remained similar (OR = 1.01, 95% CI = 0.90 to 1.13 overall; OR = 1.00, 95% CI = 0.86 to 1.15 among African American participants; and OR = 1.04, 95% CI = 0.87 to 1.24 among White participants).

Conclusions: This large-scale prospective survey revealed similar quit rates among menthol and nonmenthol smokers. Results contribute to policy discussions, especially if, as a meta-analysis suggests, lung cancer risk is higher for nonmenthol smokers and a ban leads menthol smokers to switch to nonmenthol cigarettes.
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http://dx.doi.org/10.1093/jnci/djac070DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9275766PMC
July 2022

Evaluating breast cancer predisposition genes in women of African ancestry.

Genet Med 2022 07 8;24(7):1468-1475. Epub 2022 Apr 8.

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

Purpose: Studies conducted primarily among European ancestry women reported 12 breast cancer predisposition genes. However, etiologic roles of these genes in breast cancer among African ancestry women have been less well-investigated.

Methods: We conducted a case-control study in African American women, which included 1117 breast cancer cases and 2169 cancer-free controls, and a pooled analysis, which included 7096 cases and 8040 controls of African descent. Odds ratios of associations with breast cancer risk were estimated.

Results: Using sequence data, we identified 61 pathogenic variants in 12 breast cancer predisposition genes, including 11 pathogenic variants not yet reported in previous studies. Pooled analysis showed statistically significant associations of breast cancer risk with pathogenic variants in BRCA1, BRCA2, PALB2, ATM, CHEK2, TP53, NF1, RAD51C, and RAD51D (all P < .05). The associations with BRCA1, PALB2, and RAD51D were stronger for estrogen receptor (ER)-negative than for ER-positive breast cancer (P heterogeneity < .05), whereas the association with CHEK2 was stronger for ER-positive than for ER-negative breast cancer.

Conclusion: Our study confirmed previously identified associations of breast cancer risk with BRCA1, BRCA2, PALB2, ATM, TP53, NF1, and CHEK2 and provided new evidence to extend the associations of breast cancer risk with RAD51C and RAD51D, which was identified previously in European ancestry populations, to African ancestry women.
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http://dx.doi.org/10.1016/j.gim.2022.03.015DOI Listing
July 2022

Depressive Symptoms and Incident Heart Failure Risk in the Southern Community Cohort Study.

JACC Heart Fail 2022 04 9;10(4):254-262. Epub 2022 Feb 9.

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

Objectives: This study aims to examine whether greater frequency of depressive symptoms associates with increased risk of incident heart failure (HF).

Background: Depressive symptoms associate with adverse prognosis in patients with prevalent HF. Their association with incident HF is less studied, particularly in low-income and minority individuals.

Methods: We studied 23,937 Black or White Southern Community Cohort Study participants (median age: 53 years, 70% Black, 64% women) enrolled between 2002 and 2009, without prevalent HF, receiving Centers for Medicare and Medicaid Services coverage. Cox models adjusted for traditional HF risk factors, socioeconomic and behavioral factors, social support, and antidepressant medications were used to quantify the association between depressive symptoms assessed at enrollment via the Center for Epidemiologic Studies Depression Scale (CESD-10) and incident HF ascertained from Centers for Medicare and Medicaid Services International Classification of Diseases-9th Revision (ICD-9) (code: 428.x) and ICD-10 (codes: I50, I110) codes through December 31, 2016.

Results: The median CESD-10 score was 9 (IQR: 5 to 13). Over a median 11-year follow-up, 6,081 (25%) participants developed HF. The strongest correlates of CESD-10 score were antidepressant medication use, age, and socioeconomic factors, rather than traditional HF risk factors. Greater frequency of depressive symptoms associated with increased incident HF risk (per 8-U higher CESD-10 HR: 1.04; 95% CI: 1.00 to 1.09; P = 0.038) without variation by race or sex. The association between depressive symptoms and incident HF varied by antidepressant use (interaction-P = 0.03) with increased risk among individuals not taking antidepressants.

Conclusions: In this high-risk, low-income, cohort of predominantly Black participants, greater frequency of depressive symptoms significantly associates with higher risk of incident HF.
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http://dx.doi.org/10.1016/j.jchf.2021.11.007DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8976159PMC
April 2022

Prostate cancer risk stratification improvement across multiple ancestries with new polygenic hazard score.

Prostate Cancer Prostatic Dis 2022 Feb 12. Epub 2022 Feb 12.

Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, Bethesda, MD, 20892, USA.

Background: Prostate cancer risk stratification using single-nucleotide polymorphisms (SNPs) demonstrates considerable promise in men of European, Asian, and African genetic ancestries, but there is still need for increased accuracy. We evaluated whether including additional SNPs in a prostate cancer polygenic hazard score (PHS) would improve associations with clinically significant prostate cancer in multi-ancestry datasets.

Methods: In total, 299 SNPs previously associated with prostate cancer were evaluated for inclusion in a new PHS, using a LASSO-regularized Cox proportional hazards model in a training dataset of 72,181 men from the PRACTICAL Consortium. The PHS model was evaluated in four testing datasets: African ancestry, Asian ancestry, and two of European Ancestry-the Cohort of Swedish Men (COSM) and the ProtecT study. Hazard ratios (HRs) were estimated to compare men with high versus low PHS for association with clinically significant, with any, and with fatal prostate cancer. The impact of genetic risk stratification on the positive predictive value (PPV) of PSA testing for clinically significant prostate cancer was also measured.

Results: The final model (PHS290) had 290 SNPs with non-zero coefficients. Comparing, for example, the highest and lowest quintiles of PHS290, the hazard ratios (HRs) for clinically significant prostate cancer were 13.73 [95% CI: 12.43-15.16] in ProtecT, 7.07 [6.58-7.60] in African ancestry, 10.31 [9.58-11.11] in Asian ancestry, and 11.18 [10.34-12.09] in COSM. Similar results were seen for association with any and fatal prostate cancer. Without PHS stratification, the PPV of PSA testing for clinically significant prostate cancer in ProtecT was 0.12 (0.11-0.14). For the top 20% and top 5% of PHS290, the PPV of PSA testing was 0.19 (0.15-0.22) and 0.26 (0.19-0.33), respectively.

Conclusions: We demonstrate better genetic risk stratification for clinically significant prostate cancer than prior versions of PHS in multi-ancestry datasets. This is promising for implementing precision-medicine approaches to prostate cancer screening decisions in diverse populations.
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http://dx.doi.org/10.1038/s41391-022-00497-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9372232PMC
February 2022

A pooled case-only analysis of obesity and breast cancer subtype among Black women in the southeastern United States.

Cancer Causes Control 2022 Apr 28;33(4):515-524. Epub 2022 Jan 28.

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

Purpose: To evaluate the association between obesity and the relative prevalence of tumor subtypes among Black women with breast cancer (BC).

Methods: We conducted a pooled case-only analysis of 1,793 Black women with invasive BC recruited through three existing studies in the southeastern US. Multivariable case-only polytomous logistic regression models were used to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for the association between obesity, measured by pre-diagnostic body mass index (BMI), and human epidermal growth factor receptor 2 + (HER2 +) and triple negative BC (TNBC) subtype relative to hormone receptor (HR) + /HER2- status (referent).

Results: Among 359 premenopausal women, 55.4% of cases were HR + /HER2 -, 20.1% were HER2 + , and 24.5% were TNBC; corresponding percentages among 1,434 postmenopausal women were 59.3%, 17.0%, and 23.6%. Approximately, 50-60% of both pre- and postmenopausal women were obese (BMI > 30 kg/m), regardless of BC subtype. We did not observe a significant association between obesity and BC subtype. Among postmenopausal women, class I obesity (BMI 35 + kg/m) was not associated with the development of HER2 + BC (OR 0.69; 95% CI 0.42-1.14) or TNBC (OR 0.93; 95% CI 0.60-1.45) relative to HR + /HER2- tumors. Corresponding estimates among premenopausal women were 1.03 (95% CI 0.43-2.48) and 1.13 (95% CI 0.48-2.64).

Conclusion: In this large study of Black women with BC, there was no evidence of heterogeneity of BMI by BC subtype.
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http://dx.doi.org/10.1007/s10552-021-01545-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9006670PMC
April 2022

A Rare Germline HOXB13 Variant Contributes to Risk of Prostate Cancer in Men of African Ancestry.

Eur Urol 2022 05 12;81(5):458-462. Epub 2022 Jan 12.

Department of Urology, Northwestern University, Chicago, IL, USA.

A rare African ancestry-specific germline deletion variant in HOXB13 (X285K, rs77179853) was recently reported in Martinican men with early-onset prostate cancer. Given the role of HOXB13 germline variation in prostate cancer, we investigated the association between HOXB13 X285K and prostate cancer risk in a large sample of 22 361 African ancestry men, including 11 688 prostate cancer cases. The risk allele was present only in men of West African ancestry, with an allele frequency in men that ranged from 0.40% in Ghana and 0.31% in Nigeria to 0% in Uganda and South Africa, with a range of frequencies in men with admixed African ancestry from North America and Europe (0-0.26%). HOXB13 X285K was associated with 2.4-fold increased odds of prostate cancer (95% confidence interval [CI] = 1.5-3.9, p = 2 × 10), with greater risk observed for more aggressive and advanced disease (Gleason ≥8: odds ratio [OR] = 4.7, 95% CI = 2.3-9.5, p = 2 × 10; stage T3/T4: OR = 4.5, 95% CI = 2.0-10.0, p = 2 × 10; metastatic disease: OR = 5.1, 95% CI = 1.9-13.7, p = 0.001). We estimated that the allele arose in West Africa 1500-4600 yr ago. Further analysis is needed to understand how the HOXB13 X285K variant impacts the HOXB13 protein and function in the prostate. Understanding who carries this mutation may inform prostate cancer screening in men of West African ancestry. PATIENT SUMMARY: A rare African ancestry-specific germline deletion in HOXB13, found only in men of West African ancestry, was reported to be associated with an increased risk of overall and advanced prostate cancer. Understanding who carries this mutation may help inform screening for prostate cancer in men of West African ancestry.
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http://dx.doi.org/10.1016/j.eururo.2021.12.023DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9018520PMC
May 2022

Prospective study of oral microbiome and gastric cancer risk among Asian, African American and European American populations.

Int J Cancer 2022 03 5;150(6):916-927. Epub 2021 Nov 5.

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

Colonization of specific bacteria in the human mouth was reported to be associated with gastric cancer risk. However, previous studies were limited by retrospective study designs and low taxonomic resolutions. We performed a prospective case-control study nested within three cohorts to investigate the relationship between oral microbiome and gastric cancer risk. Shotgun metagenomic sequencing was employed to characterize the microbiome in prediagnostic buccal samples from 165 cases and 323 matched controls. Associations of overall microbial richness and abundance of microbial taxa, gene families and metabolic pathways with gastric cancer risk were evaluated via conditional logistic regression. Analyses were performed within each cohort, and results were combined by meta-analyses. We found that overall microbial richness was associated with decreased gastric cancer risk, with an odds ratio (OR) per standard deviation (SD) increase in Simpson's reciprocal index of 0.77 (95% confidence interval [CI] = 0.61-0.99). Nine taxa, 38 gene families and six pathways also showed associations with gastric cancer risk at P < .05. Neisseria mucosa and Prevotella pleuritidis were enriched, while Mycoplasma orale and Eubacterium yurii were depleted among cases with ORs and 95% CIs per SD increase in centered log-ratio transformed taxa abundance of 1.31 (1.03-1.67), 1.26 (1.00-1.57), 0.74 (0.59-0.94) and 0.80 (0.65-0.98), respectively. The top two gene families (P = 3.75 × 10 and 3.91 × 10 ) and pathways (P = 1.75 × 10 and 1.53 × 10 ) associated with gastric cancer were related to the decreased risk and are involved in hexitol metabolism. Our study supports the hypothesis that oral microbiota may play a role in gastric cancer etiology.
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http://dx.doi.org/10.1002/ijc.33847DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8982516PMC
March 2022

Discovery of structural deletions in breast cancer predisposition genes using whole genome sequencing data from > 2000 women of African-ancestry.

Hum Genet 2021 Oct 27;140(10):1449-1457. Epub 2021 Aug 27.

Division of Epidemiology, Department of Medicine, Vanderbilt Epidemiology Center, Vanderbilt-Ingram Cancer Center, Vanderbilt University School of Medicine, TN, 37203-1738, Nashville, USA.

Single germline nucleotide pathogenic variants have been identified in 12 breast cancer predisposition genes, but structural deletions in these genes remain poorly characterized. We conducted in-depth whole genome sequencing (WGS) in genomic DNA samples obtained from 1340 invasive breast cancer cases and 675 controls of African ancestry. We identified 25 deletions in the intragenic regions of ten established breast cancer predisposition genes based on a consensus call from six state-of-the-art SV callers. Overall, no significant case-control difference was found in the frequency of these deletions. However, 1.0% of cases and 0.3% of controls carried any of the eight putative protein-truncating rare deletions located in BRCA1, BRCA2, CDH1, TP53, NF1, RAD51D, RAD51C and CHEK2, resulting in an odds ratio (OR) of 3.29 (95% CI 0.74-30.16). We also identified a low-frequency deletion in NF1 associated with breast cancer risk (OR 1.93, 95% CI 1.14-3.42). In addition, we detected 56 deletions, including six putative protein-truncating deletions, in suspected breast predisposition genes. This is the first large study to systematically search for structural deletions in breast cancer predisposition genes. Many of the deletions, particularly those resulting in protein truncations, are likely to be pathogenic. Results from this study, if confirmed in future large-scale studies, could have significant implications for genetic testing for this common cancer.
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http://dx.doi.org/10.1007/s00439-021-02342-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9109261PMC
October 2021

Gestational diabetes and risk of breast cancer before age 55 years.

Int J Epidemiol 2022 01;50(6):1936-1947

Epidemiology Branch, National Institute of Environmental Health Sciences, National Institutes of Health, Durham, NC, USA.

Background: The history of gestational diabetes mellitus (GDM) has been associated with breast cancer risk in some studies, particularly in young women, but results of cohort studies are conflicting.

Methods: We pooled data from 257 290 young (age <55 years) women from five cohorts. We used multivariable Cox proportional-hazards regression to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for the association between GDM history and risk of breast cancer, overall and by oestrogen receptor (ER) status, before age 55 years, adjusted for established breast cancer risk factors.

Results: Five percent of women reported a history of GDM and 6842 women reported an incident breast-cancer diagnosis (median follow-up = 16 years; maximum = 24 years). Compared with parous women without GDM, women with a history of GDM were not at increased risk of young-onset breast cancer overall (HR = 0.90; 95% CI: 0.78, 1.03) or by ER status (HR = 0.96; 95% CI: 0.79, 1.16 for ER-positive; HR = 1.07; 95% CI: 0.78, 1.47 for ER-negative). Compared with nulliparous women, parous women with a history of GDM had a lower risk of breast cancer overall (HR = 0.79; 95% CI: 0.68, 0.91) and of ER-positive (HR = 0.82; 95% CI: 0.66, 1.02) but not ER-negative (HR = 1.09; 95% CI: 0.76, 1.54) invasive breast cancer. These results were consistent with the HRs comparing parous women without GDM to nulliparous women.

Conclusions: Results of this analysis do not support the hypothesis that GDM is a risk factor for breast cancer in young women. Our findings suggest that the well-established protective effect of parity on risk of ER-positive breast cancer persists even for pregnancies complicated by GDM.
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http://dx.doi.org/10.1093/ije/dyab165DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8743115PMC
January 2022

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

Cancer Causes Control 2021 Dec 25;32(12):1423-1432. Epub 2021 Aug 25.

Division of Epidemiology, Department of Medicine, Vanderbilt Epidemiology Center, Vanderbilt-Ingram Cancer Center, Vanderbilt University School of Medicine, 1161 21st Avenue South, Nashville, TN, USA.

Purpose: 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.

Methods: 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.

Results: 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).

Conclusion: Results from this study suggest that oral microbiota may play a role in the development of lung cancer.
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http://dx.doi.org/10.1007/s10552-021-01490-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8541916PMC
December 2021

Adverse Childhood Experiences and Chronic Disease Risk in the Southern Community Cohort Study.

J Health Care Poor Underserved 2021 ;32(3):1384-1402

We used the Southern Community Cohort Study of people residing in 12 states in the southeastern United States (n=38,200 participants) to examine associations between adverse childhood experiences (ACEs) and chronic disease risk. After adjustment for confounding, there were statistically significant positive associations for people reporting four or more ACEs relative to those reporting no ACEs, and this was true for all chronic diseases except hypertension. The most elevated risk was seen for depression when measured as a yes/no variable (odds ratio (OR) 2.84, 95% confidence interval (CI) 2.64-3.06) or when using the 10-item Center for Epidemiologic Student Depression (CESD) scale (OR 1.88, 95% CI 1.75-2.02). There were also statistically significant monotonic increases in risk with worsening ACE score for all chronic diseases except hypertension, cancer, and high cholesterol. The need to establish programs that build resilience during childhood is paramount for preventing chronic diseases that may result from childhood abuse, neglect, and household dysfunction.
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http://dx.doi.org/10.1353/hpu.2021.0139DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8462987PMC
September 2021

The Association between Outdoor Artificial Light at Night and Breast Cancer Risk in Black and White Women in the Southern Community Cohort Study.

Environ Health Perspect 2021 08 11;129(8):87701. Epub 2021 Aug 11.

Occupational and Environmental Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Rockville, Maryland, USA.

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http://dx.doi.org/10.1289/EHP9381DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8357036PMC
August 2021

Racial Differences in Hepatocellular Carcinoma Incidence and Risk Factors among a Low Socioeconomic Population.

Cancers (Basel) 2021 Jul 23;13(15). Epub 2021 Jul 23.

Division of Epidemiology, Vanderbilt University Medical Center, Nashville, TN 37232, USA.

The purpose of this study was to examine differences in risk factors associated with hepatocellular carcinoma (HCC) among White and African Americans from low socioeconomic backgrounds in the Southern Community Cohort Study (SCCS). The SCCS is a prospective cohort study with participants from the southeastern US. HCC incidence rates were calculated. Multivariable Cox regression was used to calculate HCC-adjusted hazard ratios (aHR) associated with known baseline HCC risk factors for White and African Americans, separately. There were 294 incident HCC. The incidence rate ratio for HCC was higher (IRR = 1.4, 95%CI: 1.1-1.9) in African Americans compared to White Americans. White Americans saw a stronger association between self-reported hepatitis C virus (aHR = 19.24, 95%CI: 10.58-35.00) and diabetes (aHR = 3.55, 95%CI: 1.96-6.43) for the development of HCC compared to African Americans (aHR = 7.73, 95%CI: 5.71-10.47 and aHR = 1.48, 95%CI: 1.06-2.06, respectively) even though the prevalence of these risk factors was similar between races. Smoking (aHR = 2.91, 95%CI: 1.87-4.52) and heavy alcohol consumption (aHR = 1.59, 95%CI: 1.19-2.11) were significantly associated with HCC risk among African Americans only. In this large prospective cohort, we observed racial differences in HCC incidence and risk factors associated with HCC among White and African Americans.
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http://dx.doi.org/10.3390/cancers13153710DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8345125PMC
July 2021

Associations of Subtype and Isomeric Plasma Carotenoids with Prostate Cancer Risk in Low-Income African and European Americans.

Cancer Epidemiol Biomarkers Prev 2021 10 16;30(10):1846-1857. Epub 2021 Jul 16.

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

Background: Various carotenoids in circulation, including isomers, may have different influences on cancer risk.

Methods: We conducted a nested case-control study including 343 incident prostate cancer cases and 640 controls individually matched on age, race, study site, and time of blood collection. Carotenoids investigated were carotene, cryptoxanthin, lycopene, dihydrolycopene, lutein, anhydrolutein, and zeaxanthin, including α versus β configurations and versus isomers. General linear model and conditional logistic regression were applied to evaluate associations for prostate cancer risk, with adjustment for potential confounders. We conducted additional analyses with further stratification by race, multivitamin use, and smoking status.

Results: Case-control differences were found in carotenoid subtype levels, although not all reached the multiple comparison adjusted threshold for significance. Plasma lycopene [OR = 0.51; 95% confidence interval (CI), 0.29-0.87; = 0.014], dihydrolycopene (OR = 0.37; 95% CI, 0.18-0.74; = 0.006), and -anhydrolutein (OR = 0.57; 95% CI, 0.33-0.96; = 0.037) were inversely, while β--carotene (OR = 2.13; 95% CI, 1.32-3.43; = 0.002) and -lutein (OR, 1.86; 95% CI, 1.20-2.88; = 0.006) were positively associated with prostate cancer risk. Stratified analyses showed inverse associations of lycopene, dihydrolycopene, and -anhydrolutein with prostate cancer risk in subjects without multivitamin use; lycopene and dihydrolycopene in African-Americans and current smokers; and dihydrolycopene in nonsmokers. Positive associations of β--carotene and -lutein were observed in African-Americans, nonsmokers, and multivitamin users.

Conclusions: The associations of carotenoids with risk of prostate cancer differed by carotenoid subtypes.

Impact: Public health recommendations on carotenoid intakes for prostate cancer prevention should take subtypes and isomers into consideration.
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http://dx.doi.org/10.1158/1055-9965.EPI-20-1785DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8492498PMC
October 2021

Epidemiology of 40 blood biomarkers of one-carbon metabolism, vitamin status, inflammation, and renal and endothelial function among cancer-free older adults.

Sci Rep 2021 07 5;11(1):13805. Epub 2021 Jul 5.

Duke - NUS Medical School, Singapore, Singapore.

Imbalances of blood biomarkers are associated with disease, and biomarkers may also vary non-pathologically across population groups. We described variation in concentrations of biomarkers of one-carbon metabolism, vitamin status, inflammation including tryptophan metabolism, and endothelial and renal function among cancer-free older adults. We analyzed 5167 cancer-free controls aged 40-80 years from 20 cohorts in the Lung Cancer Cohort Consortium (LC3). Centralized biochemical analyses of 40 biomarkers in plasma or serum were performed. We fit multivariable linear mixed effects models to quantify variation in standardized biomarker log-concentrations across four factors: age, sex, smoking status, and body mass index (BMI). Differences in most biomarkers across most factors were small, with 93% (186/200) of analyses showing an estimated difference lower than 0.25 standard-deviations, although most were statistically significant due to large sample size. The largest difference was for creatinine by sex, which was - 0.91 standard-deviations lower in women than men (95%CI - 0.98; - 0.84). The largest difference by age was for total cysteine (0.40 standard-deviation increase per 10-year increase, 95%CI 0.36; 0.43), and by BMI was for C-reactive protein (0.38 standard-deviation increase per 5-kg/m increase, 95%CI 0.34; 0.41). For 31 of 40 markers, the mean difference between current and never smokers was larger than between former and never smokers. A statistically significant (p < 0.05) association with time since smoking cessation was observed for 8 markers, including C-reactive protein, kynurenine, choline, and total homocysteine. We conclude that most blood biomarkers show small variations across demographic characteristics. Patterns by smoking status point to normalization of multiple physiological processes after smoking cessation.
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http://dx.doi.org/10.1038/s41598-021-93214-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8257595PMC
July 2021

Cholesterol and Egg Intakes with Cardiometabolic and All-Cause Mortality among Chinese and Low-Income Black and White Americans.

Nutrients 2021 Jun 19;13(6). Epub 2021 Jun 19.

Vanderbilt Epidemiology Center, Vanderbilt University Medical Center, Department of Medicine, Division of Epidemiology, Nashville, TN 37203, USA.

We examined the associations of dietary cholesterol and egg intakes with cardiometabolic and all-cause mortality among Chinese and low-income Black and White Americans. Included were 47,789 Blacks, 20,360 Whites, and 134,280 Chinese aged 40-79 years at enrollment. Multivariable Cox models with restricted cubic splines were applied to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for mortality outcomes using intakes of 150 mg cholesterol/day and 1 egg/week as the references. Cholesterol intake showed a nonlinear association with increased all-cause mortality and a linear association with increased cardiometabolic mortality among Black Americans: HRs (95% CIs) associated with 300 and 600 mg/day vs. 150 mg/day were 1.07 (1.03-1.11) and 1.13 (1.05-1.21) for all-cause mortality (-linearity = 0.04, -nonlinearity = 0.002, and -overall < 0.001) and 1.10 (1.03-1.16) and 1.21 (1.08-1.36) for cardiometabolic mortality (-linearity = 0.007, -nonlinearity = 0.07, and -overall = 0.005). Null associations with all-cause or cardiometabolic mortality were noted for White Americans (-linearity ≥ 0.13, -nonlinearity ≥ 0.06, and -overall ≥ 0.05 for both). Nonlinear inverse associations were observed among Chinese: HR (95% CI) for 300 vs. 150 mg/day was 0.94 (0.92-0.97) for all-cause mortality and 0.91 (0.87-0.95) for cardiometabolic mortality, but the inverse associations disappeared with cholesterol intake > 500 mg/day (-linearity ≥ 0.12; -nonlinearity ≤ 0.001; -overall < 0.001 for both). Similarly, we observed a positive association of egg intake with all-cause mortality in Black Americans, but a null association in White Americans and a nonlinear inverse association in Chinese. In conclusion, the associations of cholesterol and egg intakes with cardiometabolic and all-cause mortality may differ across ethnicities who have different dietary patterns and cardiometabolic risk profiles. However, residual confounding remains possible.
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http://dx.doi.org/10.3390/nu13062094DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8234137PMC
June 2021

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

Prostate Cancer Prostatic Dis 2022 02 14;25(2):229-237. 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.
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http://dx.doi.org/10.1038/s41391-021-00403-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8669040PMC
February 2022

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 07 4;30(7):1416-1423. 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.
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http://dx.doi.org/10.1158/1055-9965.EPI-20-1784DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8254754PMC
July 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.
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http://dx.doi.org/10.1002/ijc.33598DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8594451PMC
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 06 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.
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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.
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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.
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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.
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http://dx.doi.org/10.1002/cam4.3637DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7926017PMC
February 2021
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