Publications by authors named "Dezheng Huo"

234 Publications

Assessment of Breast Cancer Management in Sub-Saharan Africa.

JCO Glob Oncol 2021 Sep;7:1593-1601

Center for Global Health, University of Chicago, Chicago IL.

Purpose: To document progress and bottlenecks in breast cancer management in sub-Saharan Africa, subsequent to a 2013 pilot survey conducted through the African Organization for Research and Treatment in Cancer (AORTIC) network.

Methods: An anonymous survey of breast cancer management was conducted in 2018 among AORTIC members. Results concerning respondent specialty, access to tumor boards, treatment accessibility, diagnostic services, and factors influencing treatment outcomes were compared with the 2013 findings.

Results: Thirty-seven respondents from 30 facilities in 21 sub-Saharan Africa countries responded. The majority (92%) were clinical oncologists. Radiotherapy facilities were available in 70% of facilities. Seventy-eight percent of these had linear accelerators, and 42% had cobalt machines. Eighty percent of facilities had multidisciplinary tumor boards. Immunohistochemistry was routinely performed in 74% of facilities, computed tomography scan in 90%, bone scan in 16%, and positron emission tomography scans in 5%. Anthracyclines, taxanes, tamoxifen, letrozole, anastrozole, and zoledronic acid were available in the majority; trastuzumab, fertility, and genetic counseling were available in 66%, 58%, and 16%, respectively. There were a 50% increase in oncologist respondents over 2013 and a > 50% increase in radiotherapy facilities, particularly linear accelerators. Availability of trastuzumab, aromatase inhibitors, and taxanes increased. Immunohistochemistry capacity remained the same, whereas facilities harvesting at least 10 axillary lymph nodes increased. Bone scan facilities decreased. Responses suggested improved diagnostic services, systemic therapies, and radiotherapy. Sociocultural and economic barriers, system delays, and advanced stage at presentation remain.

Conclusion: Clinicians in sub-Saharan Africa have basic tools to improve breast cancer outcomes, recording positive strides in domains such as radiotherapy and systemic therapy. Socioeconomic and cultural barriers and system delays persist. Workforce expansion must be prioritized to improve quality of care to improve outcomes.
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http://dx.doi.org/10.1200/GO.21.00282DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8624034PMC
September 2021

Whole-genome analysis of Nigerian patients with breast cancer reveals ethnic-driven somatic evolution and distinct genomic subtypes.

Nat Commun 2021 11 26;12(1):6946. Epub 2021 Nov 26.

Center for Clinical Cancer Genetics and Global Health, Department of Medicine, The University of Chicago, Chicago, IL, 60637, USA.

Black women across the African diaspora experience more aggressive breast cancer with higher mortality rates than white women of European ancestry. Although inter-ethnic germline variation is known, differential somatic evolution has not been investigated in detail. Analysis of deep whole genomes of 97 breast cancers, with RNA-seq in a subset, from women in Nigeria in comparison with The Cancer Genome Atlas (n = 76) reveal a higher rate of genomic instability and increased intra-tumoral heterogeneity as well as a unique genomic subtype defined by early clonal GATA3 mutations with a 10.5-year younger age at diagnosis. We also find non-coding mutations in bona fide drivers (ZNF217 and SYPL1) and a previously unreported INDEL signature strongly associated with African ancestry proportion, underscoring the need to expand inclusion of diverse populations in biomedical research. Finally, we demonstrate that characterizing tumors for homologous recombination deficiency has significant clinical relevance in stratifying patients for potentially life-saving therapies.
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http://dx.doi.org/10.1038/s41467-021-27079-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8626467PMC
November 2021

Associations between age of menarche and genetic variation in women of African descent: genome-wide association study and polygenic score analysis.

J Epidemiol Community Health 2021 Oct 27. Epub 2021 Oct 27.

Department of Public Health Sciences, University of Chicago, Chicago, Illinois, USA

Introduction: Many diseases of adulthood are associated with a woman's age at menarche. Genetic variation affects age at menarche, but it remains unclear whether in women of African ancestry the timing of menarche is regulated by genetic variants that were identified in predominantly European and East Asian populations.

Methods: We explored the genetic architecture of age at menarche in 3145 women of African ancestry who live in the USA, Barbados and Nigeria. We undertook a genome-wide association study, and evaluated the performance of previously identified variants.

Results: One variant was associated with age at menarche, a deletion at chromosome 2 (chr2:207216165) (p=1.14×10). 349 genotyped variants overlapped with these identified in populations of non-African ancestry; these replicated weakly, with 51.9% having concordant directions of effect. However, collectively, a polygenic score constructed of those previous variants was suggestively associated with age at menarche (beta=0.288 years; p=0.041). Further, this association was strong in women enrolled in the USA and Barbados (beta=0.445 years, p=0.008), but not in Nigerian women (beta=0.052 years; p=0.83).

Discussion: This study suggests that in women of African ancestry the genetic drivers of age at menarche may differ from those identified in populations of non-African ancestry, and that these differences are more pronounced in women living in Nigeria, although some associated trait loci may be shared across populations. This highlights the need for well-powered ancestry-specific genetic studies to fully characterise the genetic influences of age at menarche.
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http://dx.doi.org/10.1136/jech-2020-216000DOI Listing
October 2021

Hypofractionated Radiation Therapy for Breast Cancer: Financial Risk and Expenditures in the United States, 2008 to 2017.

Int J Radiat Oncol Biol Phys 2021 Oct 9. Epub 2021 Oct 9.

Department of Public Health Sciences, The University of Chicago, Chicago, Illinois. Electronic address:

Purpose: Rising cancer care expenditures and technological advancement of shorter radiation therapy regimens have drawn significant attention to the use of hypofractionated radiation therapy in clinical care. We examine the costs of hypofractionated whole breast irradiation (HF-WBI) compared with conventional whole breast irradiation (CF-WBI) in the United States and investigate the influences of patient characteristics and commercial insurance on HF-WBI use.

Methods And Materials: In a retrospective study using private employer-sponsored insurance claims, a pooled cross-sectional evaluation of radiation therapy in patients with commercial insurance was performed from 2008 to 2017. The study population included female patients with early-stage breast cancer treated with lumpectomy and whole breast irradiation.

Results: A total of 15,869 women received HF-WBI, and 59,328 received CF-WBI. HF-WBI use increased from 2008 to 2017. Community-level factors such as a higher proportion of college graduates and greater mixed racial composition were associated with increased HF-WBI use. Mean insurer-paid radiation therapy expenditures were significantly lower for HF-WBI versus CF-WBI (adjusted difference, $6375; 95% confidence interval, $6147-$6603). Mean patient out-of-pocket expenditure for HF-WBI was $139 less than that for CF-WBI. Geographic variation existed across the United States in HF-WBI use (range, 9.6%-36.2%), with no consistent relationship between HF-WBI use and corresponding average cost differences between HF-WBI and CF-WBI.

Conclusions: If trends continue, HF-WBI will soon become the dominant form of radiation treatment in the United States. Although HF-WBI represents significant savings to the health care system and individual patients, no evidence indicated that a financial disincentive had slowed adoption of HF-WBI. Therefore, multilevel approaches, including individuals, the community, and health policy, should be used to promote cost-effective cancer care. Innovations to policies on cost-effective radiation therapy treatment might consider non-financial incentives to promote HF-WBI use.
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http://dx.doi.org/10.1016/j.ijrobp.2021.10.005DOI Listing
October 2021

The impact of coronavirus disease 2019 on the quality of life and treatment disruption of patients with breast cancer in a multiethnic cohort.

Cancer 2021 11 22;127(21):4072-4080. Epub 2021 Jul 22.

Department of Public Health Sciences, University of Chicago, Chicago, Illinois.

Background: As the coronavirus disease 2019 (COVID-19) pandemic continues to spread, it remains unclear how vulnerable populations with preexisting health conditions like cancer have been affected.

Methods: Between July and September of 2020, the authors conducted a cross-sectional study that surveyed 2661 patients with breast cancer who were registered in the Chicago Multiethnic Epidemiologic Breast Cancer Cohort and received 1300 responses (71.5% White patients and 22.4% Black patients). The survey measured the psychosocial well-being of participants before and during the COVID-19 pandemic and examined whether they experienced any type of financial challenges or treatment disruption.

Results: The results indicated that feelings of isolation increased significantly during the pandemic. Meanwhile, the overall median isolation/stress score was 1.2 on a scale from 0 (never) to 4 (always), which was not significantly different between White patients and Black patients. One-third of patients experienced some type of financial challenge during this time. Medicaid recipients, of whom almost 80% were Black, were more likely to experience financial challenges. In addition, approximately one-fourth of patients experienced difficulty getting treatment.

Conclusions: This study indicates that the quality of life of patients with breast cancer and their scheduled treatments have been adversely affected during the COVID-19 pandemic. These findings suggest that more support should be provided by hospital centers and the medical research community to patients with cancer during this challenging pandemic.

Lay Summary: The authors surveyed patients with breast cancer in Chicago using a questionnaire to examine how their lives have been affected during the coronavirus disease 2019 (COVID-19) pandemic. The results indicate that the lives of patients with breast cancer and their scheduled treatments have been adversely affected during the pandemic. In addition, patients who were covered by Medicaid, most of whom were Black, were more likely to experience financial challenges. The findings suggest that hospital centers and the medical research community should reach out and provide more information to support patients with cancer during this challenging pandemic.
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http://dx.doi.org/10.1002/cncr.33798DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8426957PMC
November 2021

The impact of site-specific digital histology signatures on deep learning model accuracy and bias.

Nat Commun 2021 07 20;12(1):4423. Epub 2021 Jul 20.

Section of Hematology/Oncology, Department of Medicine, University of Chicago, Chicago, IL, USA.

The Cancer Genome Atlas (TCGA) is one of the largest biorepositories of digital histology. Deep learning (DL) models have been trained on TCGA to predict numerous features directly from histology, including survival, gene expression patterns, and driver mutations. However, we demonstrate that these features vary substantially across tissue submitting sites in TCGA for over 3,000 patients with six cancer subtypes. Additionally, we show that histologic image differences between submitting sites can easily be identified with DL. Site detection remains possible despite commonly used color normalization and augmentation methods, and we quantify the image characteristics constituting this site-specific digital histology signature. We demonstrate that these site-specific signatures lead to biased accuracy for prediction of features including survival, genomic mutations, and tumor stage. Furthermore, ethnicity can also be inferred from site-specific signatures, which must be accounted for to ensure equitable application of DL. These site-specific signatures can lead to overoptimistic estimates of model performance, and we propose a quadratic programming method that abrogates this bias by ensuring models are not trained and validated on samples from the same site.
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http://dx.doi.org/10.1038/s41467-021-24698-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8292530PMC
July 2021

Prenatal Diethylstilbestrol Exposure and Cancer Risk in Males.

Cancer Epidemiol Biomarkers Prev 2021 Oct 16;30(10):1826-1833. Epub 2021 Jul 16.

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

Background: The influence of prenatal diethylstilbestrol (DES) exposure on cancer incidence among middle-aged men has not been well-characterized. We investigated whether exposure to DES before birth impacts overall cancer risk, and risk of site-specific cancers.

Methods: Men (mean age in 2016 = 62.0 years) who were or were not prenatally DES exposed were identified between 1953 and 1994 and followed for cancer primarily via questionnaire approximately every 5 years between 1994 and 2016. The overall and site-specific cancer rates of the two groups were compared using Poisson regression and proportional hazards modeling with adjustment for age.

Results: DES exposure was not associated with either overall cancer [hazard ratio (HR), 0.94; 95% confidence interval (CI), 0.77-1.15] or total prostate cancer rates (HR, 0.95; 95% CI, 0.68-1.33), but was inversely associated with urinary tract cancer incidence (HR, 0.48; 95% CI, 0.23-1.00).

Conclusions: There was no increase in either overall or prostate cancer rates among men prenatally DES exposed relative to those unexposed. An unexpected risk reduction was observed for urinary system cancers among the exposed relative to those unexposed. These findings suggest that prenatal DES exposure is unlikely to be an important contributor to cancer development in middle-aged men.

Impact: The results of this study could lend reassurance to middle-aged men who were prenatally DES exposed that their exposure does not adversely influence their overall cancer risk.
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http://dx.doi.org/10.1158/1055-9965.EPI-21-0234DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8492497PMC
October 2021

Has Hypofractionated Whole-Breast Radiation Therapy Become the Standard of Care in the United States? An Updated Report from National Cancer Database.

Clin Breast Cancer 2022 Jan 7;22(1):e8-e20. Epub 2021 Jun 7.

Department of Public Health Sciences, University of Chicago, Chicago, IL. Electronic address:

Introduction/background: We aimed to update the previous evaluation of hypofractionated whole-breast irradiation (HF-WBI) use over time in the United States and factors related to its adoption for patients undergoing a lumpectomy from 2004 to 2016.

Materials And Methods: Among the patients who underwent a lumpectomy, we identified 688,079 patients with early-stage invasive breast cancer and 248,218 patients with ductal carcinoma in situ in the National Cancer Database from 2004 to 2016. We defined HF-WBI as 2.5 to 3.33 Gy/fraction to the breast and conventional fractionated whole-breast irradiation as 1.8 to 2.0 Gy/fraction. We evaluated the trend of HF-WBI use and examined factors associated with HF-WBI use using logistic regression models.

Results: Among invasive cancer patients, the use of HF-WBI increased exponentially from 0.7% in 2004 to 15.6% in 2013 and then to 38.1% in 2016. Among patients with ductal carcinoma in situ, the use of HF-WBI has increased significantly from 0.42% in 2004 to 13.4% in 2013 and then to 34.3% in 2016. Factors found to be associated with HF-WBI use included age, patient geographical location, race/ethnicity, tumor stage, grade, treating facility type, and volume.

Conclusion: HF-WBI use in the United States has more than doubled from 2013 to 2016. Although its use is close to that of conventional fractionated whole-breast irradiation, HF-WBI is still far from the preferred standard of care in the United States. We identified several patient and facility factors that can impact the uptake of HF-WBI treatment. Microabstract Using the National Cancer Database from 2004 to 2016, we evaluated the trend of hypofractionated whole-breast radiation therapy use and factors associated with use. Use in the United States has more than doubled from 2013 to 2016, but it has not become the standard of care. We identified several patient and facility factors that impact the uptake of hypofractionated whole-breast radiation therapy treatment.
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http://dx.doi.org/10.1016/j.clbc.2021.05.016DOI Listing
January 2022

Cross-ancestry GWAS meta-analysis identifies six breast cancer loci in African and European ancestry women.

Nat Commun 2021 07 7;12(1):4198. Epub 2021 Jul 7.

Department of Epidemiology, Gillings School of Global Public Health, University of North Carolina, Chapel Hill, NC, USA.

Our study describes breast cancer risk loci using a cross-ancestry GWAS approach. We first identify variants that are associated with breast cancer at P < 0.05 from African ancestry GWAS meta-analysis (9241 cases and 10193 controls), then meta-analyze with European ancestry GWAS data (122977 cases and 105974 controls) from the Breast Cancer Association Consortium. The approach identifies four loci for overall breast cancer risk [1p13.3, 5q31.1, 15q24 (two independent signals), and 15q26.3] and two loci for estrogen receptor-negative disease (1q41 and 7q11.23) at genome-wide significance. Four of the index single nucleotide polymorphisms (SNPs) lie within introns of genes (KCNK2, C5orf56, SCAMP2, and SIN3A) and the other index SNPs are located close to GSTM4, AMPD2, CASTOR2, and RP11-168G16.2. Here we present risk loci with consistent direction of associations in African and European descendants. The study suggests that replication across multiple ancestry populations can help improve the understanding of breast cancer genetics and identify causal variants.
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http://dx.doi.org/10.1038/s41467-021-24327-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8263739PMC
July 2021

Development and external validation of a breast cancer absolute risk prediction model in Chinese population.

Breast Cancer Res 2021 05 29;23(1):62. Epub 2021 May 29.

Department of Epidemiology and Biostatistics, School of Public Health, Peking University Health Science Center, 38 Xueyuan Road, Beijing, 100191, China.

Backgrounds: In contrast to developed countries, breast cancer in China is characterized by a rapidly escalating incidence rate in the past two decades, lower survival rate, and vast geographic variation. However, there is no validated risk prediction model in China to aid early detection yet.

Methods: A large nationwide prospective cohort, China Kadoorie Biobank (CKB), was used to evaluate relative and attributable risks of invasive breast cancer. A total of 300,824 women free of any prior cancer were recruited during 2004-2008 and followed up to Dec 31, 2016. Cox models were used to identify breast cancer risk factors and build a relative risk model. Absolute risks were calculated by incorporating national age- and residence-specific breast cancer incidence and non-breast cancer mortality rates. We used an independent large prospective cohort, Shanghai Women's Health Study (SWHS), with 73,203 women to externally validate the calibration and discriminating accuracy.

Results: During a median of 10.2 years of follow-up in the CKB, 2287 cases were observed. The final model included age, residence area, education, BMI, height, family history of overall cancer, parity, and age at menarche. The model was well-calibrated in both the CKB and the SWHS, yielding expected/observed (E/O) ratios of 1.01 (95% confidence interval (CI), 0.94-1.09) and 0.94 (95% CI, 0.89-0.99), respectively. After eliminating the effect of age and residence, the model maintained moderate but comparable discriminating accuracy compared with those of some previous externally validated models. The adjusted areas under the receiver operating curve (AUC) were 0.634 (95% CI, 0.608-0.661) and 0.585 (95% CI, 0.564-0.605) in the CKB and the SWHS, respectively.

Conclusions: Based only on non-laboratory predictors, our model has a good calibration and moderate discriminating capacity. The model may serve as a useful tool to raise individuals' awareness and aid risk-stratified screening and prevention strategies.
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http://dx.doi.org/10.1186/s13058-021-01439-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8164768PMC
May 2021

Evaluating Polygenic Risk Scores for Breast Cancer in Women of African Ancestry.

J Natl Cancer Inst 2021 Sep;113(9):1168-1176

Department of Oncology, Centre for Cancer Genetic Epidemiology, University of Cambridge, Cambridge, UK.

Background: Polygenic risk scores (PRSs) have been demonstrated to identify women of European, Asian, and Latino ancestry at elevated risk of developing breast cancer (BC). We evaluated the performance of existing PRSs trained in European ancestry populations among women of African ancestry.

Methods: We assembled genotype data for women of African ancestry, including 9241 case subjects and 10 193 control subjects. We evaluated associations of 179- and 313-variant PRSs with overall and subtype-specific BC risk. PRS discriminatory accuracy was assessed using area under the receiver operating characteristic curve. We also evaluated a recalibrated PRS, replacing the index variant with variants in each region that better captured risk in women of African ancestry and estimated lifetime absolute risk of BC in African Americans by PRS category.

Results: For overall BC, the odds ratio per SD of the 313-variant PRS (PRS313) was 1.27 (95% confidence interval [CI] = 1.23 to 1.31), with an area under the receiver operating characteristic curve of 0.571 (95% CI = 0.562 to 0.579). Compared with women with average risk (40th-60th PRS percentile), women in the top decile of PRS313 had a 1.54-fold increased risk (95% CI = 1.38-fold to 1.72-fold). By age 85 years, the absolute risk of overall BC was 19.6% for African American women in the top 1% of PRS313 and 6.7% for those in the lowest 1%. The recalibrated PRS did not improve BC risk prediction.

Conclusion: The PRSs stratify BC risk in women of African ancestry, with attenuated performance compared with that reported in European, Asian, and Latina populations. Future work is needed to improve BC risk stratification for women of African ancestry.
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http://dx.doi.org/10.1093/jnci/djab050DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8418423PMC
September 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

Impact of post-diagnosis weight change on survival outcomes in Black and White breast cancer patients.

Breast Cancer Res 2021 02 4;23(1):18. Epub 2021 Feb 4.

Section of Hematology and Oncology, Department of Medicine, University of Chicago, Chicago, IL, USA.

Purpose: To evaluate weight change patterns over time following the diagnosis of breast cancer and to examine the association of post-diagnosis weight change and survival outcomes in Black and White patients.

Methods: The study included 2888 women diagnosed with non-metastatic breast cancer in 2000-2017 in Chicago. Longitudinal repeated measures of weight and height were collected, along with a questionnaire survey including questions on body size. Multilevel mixed-effects models were used to examine changes in body mass index (BMI). Delayed entry Cox proportional hazards models were used to investigate the impacts of changing slope of BMI on survival outcomes.

Results: At diagnosis, most patients were overweight or obese with a mean BMI of 27.5 kg/m and 31.5 kg/m for Blacks and Whites, respectively. Notably, about 45% of the patients had cachexia before death and substantial weight loss started about 30 months before death. In multivariable-adjusted analyses, compared to stable weight, BMI loss (> 0.5 kg/m/year) showed greater than 2-fold increased risk in overall survival (hazard ratio [HR] = 2.60, 95% CI 1.88-3.59), breast cancer-specific survival (HR = 3.05, 95% CI 1.91-4.86), and disease-free survival (HR = 2.12, 95% CI 1.52-2.96). The associations were not modified by race, age at diagnosis, and pre-diagnostic weight. BMI gain (> 0.5 kg/m/year) was also related to worse survival, but the effect was weak (HR = 1.60, 95% CI 1.10-2.33 for overall survival).

Conclusion: BMI loss is a strong predictor of worse breast cancer outcomes. Growing prevalence of obesity may hide diagnosis of cancer cachexia, which can occur in a large proportion of breast cancer patients long before death.
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http://dx.doi.org/10.1186/s13058-021-01397-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7863526PMC
February 2021

Prenatal diethylstilbestrol exposure and risk of diabetes, gallbladder disease, and pancreatic disorders and malignancies.

J Dev Orig Health Dis 2021 08 28;12(4):619-626. Epub 2020 Oct 28.

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

Prenatal diethylstilbestrol (DES) exposure is associated with increased risk of hormonally mediated cancers and other medical conditions. We evaluated the association between DES and risk of pancreatic cancer and pancreatic disorders, type 2 diabetes, and gallbladder disease, which may be involved with this malignancy. Our analyses used follow-up data from the US National Cancer Institute DES Combined Cohort Study. Cox proportional hazards models estimated hazard ratios (HRs) and 95% confidence intervals (CIs) adjusted for age, sex, cohort, body mass index, smoking, and alcohol for the association between prenatal DES exposure and type 2 diabetes, gallbladder disease (mainly cholelithiasis), pancreatic disorders (mainly pancreatitis), and pancreatic cancer among 5667 exposed and 3315 unexposed individuals followed from 1990 to 2017. Standardized incidence rate (SIR) ratios for pancreatic cancer were based on age-, race-, and calendar year-specific general population cancer incidence rates. In women and men combined, the hazards for total pancreatic disorders and pancreatitis were greater in the prenatally DES exposed than the unexposed (HR = 11, 95% CI 2.6-51 and HR = 7.0, 95% CI 1.5-33, respectively). DES was not associated overall with gallbladder disease (HR = 1.2, 95% CI 0.88-1.5) or diabetes (HR = 1.1, 95% CI 0.9-1.2). In women, but not in men, DES exposure was associated with increased risk of pancreatic cancer compared with the unexposed (HR: 4.1, 95% CI 0.84-20) or general population (SIR: 1.9, 95% CI 1.0-3.2). Prenatal DES exposure may increase the risk of pancreatic disorders, including pancreatitis in women and men. The data suggested elevated pancreatic cancer risk in DES-exposed women, but not in exposed men.
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http://dx.doi.org/10.1017/S2040174420000872DOI Listing
August 2021

Racial disparities in survival outcomes among breast cancer patients by molecular subtypes.

Breast Cancer Res Treat 2021 Feb 27;185(3):841-849. Epub 2020 Oct 27.

Department of Public Health Sciences, University of Chicago, Chicago, IL, USA.

Purpose: Differences in tumor biology, genomic architecture, and health care delivery patterns contribute to the breast cancer mortality gap between White and Black patients in the US. Although this gap has been well documented in previous literature, it remains uncertain how large the actual effect size of race is for different survival outcomes and the four breast cancer subtypes.

Methods: We established a breast cancer patient cohort at the University of Chicago Comprehensive Cancer Center. We chose five major survival outcomes to study: overall survival, recurrence-free survival, breast-cancer-specific survival, time-to-recurrence and post-recurrence survival. Cox proportional hazards models were used to estimate the hazard ratios between Black and White patients, adjusting for selected patient, tumor, and treatment characteristics, and also stratified by the four breast cancer subtypes.

Results: The study included 2795 stage I-III breast cancer patients (54% White and 38% Black). After adjusting for selected patient, tumor and treatment characteristics, Black patients still did worse than White patients in all five survival outcomes. The racial difference was highest within the HR-/HER2+ subgroup, in both overall survival (hazard ratio = 4.00, 95% CI 1.47-10.86) and recurrence-free survival (hazard ratio = 3.00, 95% CI 1.36-6.60), adjusting for age at diagnosis, cancer stage, and comorbidities. There was also a significant racial disparity within the HR+/HER2- group in both overall survival and recurrence-free survival.

Conclusions: Our study confirmed that racial disparity existed between White and Black breast cancer patients in terms of both survival and recurrence, and found that this disparity was largest among HR-/HER2+ and HR+/HER2- patients.
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http://dx.doi.org/10.1007/s10549-020-05984-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7925344PMC
February 2021

Circulating Insulin-Like Growth Factor-1 and Risk of Total and 19 Site-Specific Cancers: Cohort Study Analyses from the UK Biobank.

Cancer Epidemiol Biomarkers Prev 2020 11 20;29(11):2332-2342. Epub 2020 Aug 20.

Department of Public Health Sciences, University of Chicago, Chicago, Illinois.

Background: Insulin-like growth factor-1 (IGF-1) has been implicated in several malignancies, but few studies have examined multiple cancers simultaneously. We sought to conduct systematic assessments of the association between IGF-1 and cancer risk.

Methods: We conducted a prospective analysis between IGF-1 and incident total and 19 site-specific cancers among 412,645 individuals enrolled in the UK Biobank with follow-up to 2016. IGF-1 was measured using blood samples provided at the baseline examination. HR and 95% confidence interval (CI) were calculated with multivariable-adjusted Cox models with IGF-1 modeled both in sex-specific quintiles and continuously.

Results: Participants were followed for a median of 7.2 years. We observed positive associations between circulating IGF-1 and overall cancer risk for both men (HR = 1.03 per 5-nmol/L increment in IGF-1; 95% CI, 1.01-1.06) and women (HR = 1.03; 95% CI, 1.01-1.06). For specific sites, we observed positive associations for breast (HR = 1.10; 95% CI, 1.07-1.14), prostate (1.09; 95% CI, 1.05-1.12), colorectum (1.07; 95% CI, 1.02-1.11), melanoma (1.08; 95% CI, 1.01-1.15), kidney (1.10; 95% CI, 1.00-1.20), and thyroid (1.22; 95% CI, 1.05-1.42) and inverse associations for lung (0.91; 95% CI, 0.86-0.96), ovaries (0.86; 95% CI, 0.77-0.95), head and neck (0.90; 95% CI, 0.82-0.99), and liver (0.32; 95% CI, 0.26-0.38). The inverse association between IGF-1 and lung cancer was observed only in ever-smokers (HR = 0.88 vs. HR = 1.14; = 0.0005). Analyses comparing extreme quintiles were consistent.

Conclusions: IGF-1 is modestly associated with increased risk of total cancer in both men and women but demonstrated divergent associations for site-specific cancers.

Impact: Our study suggests that IGF-1 could serve as a target for cancer prevention or treatment.
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http://dx.doi.org/10.1158/1055-9965.EPI-20-0743DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7642199PMC
November 2020

Germline HOXB13 mutations p.G84E and p.R217C do not confer an increased breast cancer risk.

Sci Rep 2020 06 16;10(1):9688. Epub 2020 Jun 16.

Department of Gynecology and Obstetrics, University of Tübingen, Tübingen, Germany.

In breast cancer, high levels of homeobox protein Hox-B13 (HOXB13) have been associated with disease progression of ER-positive breast cancer patients and resistance to tamoxifen treatment. Since HOXB13 p.G84E is a prostate cancer risk allele, we evaluated the association between HOXB13 germline mutations and breast cancer risk in a previous study consisting of 3,270 familial non-BRCA1/2 breast cancer cases and 2,327 controls from the Netherlands. Although both recurrent HOXB13 mutations p.G84E and p.R217C were not associated with breast cancer risk, the risk estimation for p.R217C was not very precise. To provide more conclusive evidence regarding the role of HOXB13 in breast cancer susceptibility, we here evaluated the association between HOXB13 mutations and increased breast cancer risk within 81 studies of the international Breast Cancer Association Consortium containing 68,521 invasive breast cancer patients and 54,865 controls. Both HOXB13 p.G84E and p.R217C did not associate with the development of breast cancer in European women, neither in the overall analysis (OR = 1.035, 95% CI = 0.859-1.246, P = 0.718 and OR = 0.798, 95% CI = 0.482-1.322, P = 0.381 respectively), nor in specific high-risk subgroups or breast cancer subtypes. Thus, although involved in breast cancer progression, HOXB13 is not a material breast cancer susceptibility gene.
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http://dx.doi.org/10.1038/s41598-020-65665-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7297796PMC
June 2020

Guidelines for Reporting of Figures and Tables for Clinical Research in Urology.

BJU Int 2020 07 15;126(1):14-25. Epub 2020 Jun 15.

Vanderbilt University School of Medicine, Nashville, TN, USA.

In an effort to improve the presentation of and information within tables and figures in clinical urology research, we propose a set of appropriate guidelines. We introduce six principles: (1) include graphs only if they improve the reader's ability to understand the study findings; (2) think through how a graph might best convey information, do not just select a graph from preselected options on statistical software; (3) do not use graphs to replace reporting key numbers in the text of a paper; (4) graphs should give an immediate visual impression of the data; (5) make it beautiful; and (6) make the labels and legend clear and complete. We present a list of quick "dos and don'ts" for both tables and figures. Investigators should feel free to break any of the guidelines if it would result in a beautiful figure or a clear table that communicates data effectively. That said, we believe that the quality of tables and figures in the medical literature would improve if these guidelines were to be followed. PATIENT SUMMARY: A set of guidelines were developed for presenting figures and tables in urology research. The guidelines were developed by a broad group of statistical experts with special interest in urology.
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http://dx.doi.org/10.1111/bju.15102DOI Listing
July 2020

Propensity score analysis of the prognostic value of genomic assays for breast cancer in diverse populations using the National Cancer Data Base.

Cancer 2020 09 10;126(17):4013-4022. Epub 2020 Jun 10.

Section of Hematology and Oncology, Center for Clinical Cancer Genetics and Global Health, The University of Chicago, Chicago, Illinois, USA.

Background: Genomic assays such as Oncotype Dx (ODX) and MammaPrint are used for risk-adapted treatment decisions among patients with early breast cancer. However, to the authors' knowledge, concordance between genomic assays is modest. Using real-world data, the authors performed a comparative analysis of ODX and MammaPrint.

Methods: A cohort of women diagnosed with early-stage, hormone receptor-positive breast cancer who received ODX or MammaPrint was established using the National Cancer Data Base (NCDB) for 2010 through 2016. Using the propensity score matching method, 2 groups of patients with similar clinical and demographic characteristics were defined: one group received ODX and the other received MammaPrint. The authors examined the association between use of the ODX or MammaPrint assays and overall survival using Cox models.

Results: Of the 451,693 eligible patients, approximately 45.3% received ODX and 1.8% received MammaPrint testing. The use of ODX increased from 36.1% in 2010 to 49.9% in 2016, whereas use of MammaPrint increased from 0.5% in 2010 to 3.3% in 2016. The authors matched 5042 patients who received ODX with 5042 patients who received MammaPrint. The 5-year risks of death for the MammaPrint low-risk group and the ODX low-risk group were 3.4% and 4.7%, respectively. The prognostic value of MammaPrint was similar to that of ODX; the C-index was 0.614 (95% confidence interval, 0.572-0.657) for MammaPrint and 0.581 (95% confidence interval, 0.530-0.631) for ODX. There was a difference in the performance of the ODX assay observed across racial and/or ethnic groups (P < .001), with a slightly better performance noted among white compared with African American and Hispanic individuals.

Conclusions: Both the ODX and MammaPrint tests are good at identifying low-risk individuals who could be spared chemotherapy. The suboptimal performance of ODX in ethnic minority individuals deserves further investigation.
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http://dx.doi.org/10.1002/cncr.32956DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7423613PMC
September 2020

Guidelines for Reporting of Figures and Tables for Clinical Research in Urology.

Eur Urol 2020 07 22;78(1):97-109. Epub 2020 May 22.

Vanderbilt University School of Medicine, Nashville, TN, USA.

In an effort to improve the presentation of and information within tables and figures in clinical urology research, we propose a set of appropriate guidelines. We introduce six principles: (1) include graphs only if they improve the reader's ability to understand the study findings; (2) think through how a graph might best convey information, do not just select a graph from preselected options on statistical software; (3) do not use graphs to replace reporting key numbers in the text of a paper; (4) graphs should give an immediate visual impression of the data; (5) make it beautiful; and (6) make the labels and legend clear and complete. We present a list of quick "dos and don'ts" for both tables and figures. Investigators should feel free to break any of the guidelines if it would result in a beautiful figure or a clear table that communicates data effectively. That said, we believe that the quality of tables and figures in the medical literature would improve if these guidelines were to be followed. PATIENT SUMMARY: A set of guidelines were developed for presenting figures and tables in urology research. The guidelines were developed by a broad group of statistical experts with special interest in urology.
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http://dx.doi.org/10.1016/j.eururo.2020.04.048DOI Listing
July 2020

Guidelines for Reporting of Figures and Tables for Clinical Research in Urology.

Urology 2020 08 14;142:1-13. Epub 2020 May 14.

Vanderbilt University School of Medicine, Nashville, TN.

In an effort to improve the presentation of and information within tables and figures in clinical urology research, we propose a set of appropriate guidelines. We introduce 6 principles (1) include graphs only if they improve the reader's ability to understand the study findings; (2) think through how a graph might best convey information, do not just select a graph from preselected options on statistical software; (3) do not use graphs to replace reporting key numbers in the text of a paper; (4) graphs should give an immediate visual impression of the data; (5) make it beautiful; and (6) make the labels and legend clear and complete. We present a list of quick "dos and don'ts" for both tables and figures. Investigators should feel free to break any of the guidelines if it would result in a beautiful figure or a clear table that communicates data effectively. That said, we believe that the quality of tables and figures in the medical literature would improve if these guidelines were to be followed. PATIENT SUMMARY: A set of guidelines were developed for presenting figures and tables in urology research. The guidelines were developed by a broad group of statistical experts with special interest in urology.
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http://dx.doi.org/10.1016/j.urology.2020.05.002DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7387170PMC
August 2020

Guidelines for Reporting of Figures and Tables for Clinical Research in Urology.

J Urol 2020 07 22;204(1):121-133. Epub 2020 May 22.

Vanderbilt University School of Medicine, Nashville, Tennessee.

In an effort to improve the presentation of and information within tables and figures in clinical urology research, we propose a set of appropriate guidelines. We introduce six principles: (1) include graphs only if they improve the reader's ability to understand the study findings; (2) think through how a graph might best convey information, do not just select a graph from preselected options on statistical software; (3) do not use graphs to replace reporting key numbers in the text of a paper; (4) graphs should give an immediate visual impression of the data; (5) make it beautiful; and (6) make the labels and legend clear and complete. We present a list of quick "dos and don'ts" for both tables and figures. Investigators should feel free to break any of the guidelines if it would result in a beautiful figure or a clear table that communicates data effectively. That said, we believe that the quality of tables and figures in the medical literature would improve if these guidelines were to be followed. Patient summary: A set of guidelines were developed for presenting figures and tables in urology research. The guidelines were developed by a broad group of statistical experts with special interest in urology.
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http://dx.doi.org/10.1097/JU.0000000000001096DOI Listing
July 2020

Clinical evaluation of germline polymorphisms associated with capecitabine toxicity in breast cancer: TBCRC-015.

Breast Cancer Res Treat 2020 Jun 6;181(3):623-633. Epub 2020 May 6.

The University of Chicago, 5841 S. Maryland Avenue, MC 2115, Chicago, IL, 60637, USA.

Purpose: Capecitabine is important in breast cancer treatment but causes diarrhea and hand-foot syndrome (HFS), affecting adherence and quality of life. We sought to identify pharmacogenomic predictors of capecitabine toxicity using a novel monitoring tool.

Methods: Patients with metastatic breast cancer were prospectively treated with capecitabine (2000 mg/m/day, 14 days on/7 off). Patients completed in-person toxicity questionnaires (day 1/cycle) and automated phone-in assessments (days 8, 15). Correlation of genotypes with early and overall toxicity was the primary endpoint.

Results: Two hundred and fifty-nine patients were enrolled (14 institutions). Diarrhea and HFS occurred in 52% (17% grade 3) and 69% (9% grade 3), respectively. Only 29% of patients completed four cycles without dose reduction/interruption. In 39%, the highest toxicity grade was captured via phone. Three single nucleotide polymorphisms (SNPs) associated with diarrhea-DPYD*5 (odds ratio [OR] 4.9; P = 0.0005), a MTHFR missense SNP (OR 3.3; P = 0.02), and a SNP upstream of MTRR (OR 3.0; P = 0.03). GWAS elucidated a novel HFS SNP (OR 3.0; P = 0.0007) near TNFSF4 (OX40L), a gene implicated in autoimmunity including autoimmune skin diseases never before implicated in HFS. Genotype-gene expression analyses of skin tissues identified rs11158568 (associated with HFS via GWAS) with expression of CHURC1, a transcriptional activator controlling fibroblast growth factor (beta = - 0.74; P = 1.46 × 10), representing a previously unidentified mechanism for HFS.

Conclusions: This is the first cancer pharmacogenomic study to use phone-in self-reporting, permitting augmented toxicity characterization. Three germline toxicity SNPs were replicated, and several novel SNPs/genes having strong functional relevance were discovered. If further validated, these markers could permit personalized capecitabine dosing.
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http://dx.doi.org/10.1007/s10549-020-05603-8DOI Listing
June 2020

Traditional medicine usage among adult women in Ibadan, Nigeria: a cross-sectional study.

BMC Complement Med Ther 2020 Mar 20;20(1):93. Epub 2020 Mar 20.

Center for Clinical Cancer Genetics and Global Health, Department of Medicine, University of Chicago, Chicago, IL, USA.

Background: Previous research has revealed high rates of traditional medicine usage in Nigeria. Reports of widespread contamination of herbal medicine products and higher rates of noncompliance with Western medications among traditional medicine users have raised concerns about the safety of traditional medicine use. Few studies have explored how demographic factors predict rates of traditional medicine use in the general population.

Methods: We conducted interviews of 748 adult women recruited from the communities in the city of Ibadan, Nigeria from 2013 to 2015. A structured questionnaire was created to collect data on rates of traditional medicine use and demographic factors such as age, education, ethnicity, and occupation. Multivariate logistic regressions were run to examine factors related to traditional medicine use, and the effects were measured with odds ratios (OR) along with 95% confidence interval (95%CI).

Results: The overall proportion of traditional medicine use was 81.6%. Women from the Ibo and Hausa ethnic groups were significantly less likely to use traditional medicine than the majority Yoruba group (OR 0.25, 95%CI 0.10-0.63;, OR 0.43, 95%CI 0.24-0.76) respectively). In addition, educated women were less likely than their non-educated counterparts to have used traditional medicine, with the biggest effect seen in women with a secondary education (OR 0.42, 95%CI 0.21-0.85).

Conclusions: We found a high rate of traditional medicine usage, consistent with that found in prior research. A novel finding was the significance of ethnicity as a predictor for usage rates.
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http://dx.doi.org/10.1186/s12906-020-02881-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7083039PMC
March 2020

Gender Identity and Sexual Orientation Identity in Women and Men Prenatally Exposed to Diethylstilbestrol.

Arch Sex Behav 2020 02 23;49(2):447-454. Epub 2020 Jan 23.

Departments of Epidemiology and Pediatrics, Geisel School of Medicine at Dartmouth, Lebanon, NH, USA.

We assessed the associations of prenatal diethylstilbestrol (DES) exposure, a potent estrogen, with sexual orientation and gender identity in 3306 women and 1848 men who participated in a study of prenatal DES exposure. Odds ratios (OR) and 95% confidence intervals (CI) were derived from logistic regression models adjusted for birth year, study cohort, and education. Among women, the OR for DES in relation to reporting sexual orientation identity as nonheterosexual was 0.61 (95% CI 0.40-0.92) primarily due to a strong inverse association with a lesbian identity (OR 0.44, 95% CI 0.25-0.76). Among men, the OR for DES in relation to reporting a nonheterosexual sexual orientation identity was 1.4 (95% CI 0.82-2.4), and ORs were similar for having a gay identity (1.4, 95% CI 0.72-2.85) and bisexual identity (1.4, 95% CI 0.57-3.5). Only five individuals reported a gender identity not conforming to that assigned at birth, preventing meaningful analysis. Women who were prenatally exposed to DES were less likely to have a lesbian or bisexual orientation, while DES-exposed men were somewhat more likely to report being gay or bisexual, but estimates were imprecise.
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http://dx.doi.org/10.1007/s10508-020-01637-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7031187PMC
February 2020

Prevalence of Inherited Mutations in Breast Cancer Predisposition Genes among Women in Uganda and Cameroon.

Cancer Epidemiol Biomarkers Prev 2020 02 23;29(2):359-367. Epub 2019 Dec 23.

Center for Clinical Cancer Genetics and Global Health, Department of Medicine, The University of Chicago, Chicago, Illinois.

Background: Sub-Saharan Africa (SSA) has a high proportion of premenopausal hormone receptor negative breast cancer. Previous studies reported a strikingly high prevalence of germline mutations in and among Nigerian patients with breast cancer. It is unknown if this exists in other SSA countries.

Methods: Breast cancer cases, unselected for age at diagnosis and family history, were recruited from tertiary hospitals in Kampala, Uganda and Yaoundé, Cameroon. Controls were women without breast cancer recruited from the same hospitals and age-matched to cases. A multigene sequencing panel was used to test for germline mutations.

Results: There were 196 cases and 185 controls with a mean age of 46.2 and 46.6 years for cases and controls, respectively. Among cases, 15.8% carried a pathogenic or likely pathogenic mutation in a breast cancer susceptibility gene: 5.6% in , 5.6% in , 1.5% in , 1% in , 0.5% in , 0.5% in , and 0.5% in . Among controls, 1.6% carried a mutation in one of these genes. Cases were 11-fold more likely to carry a mutation compared with controls (OR = 11.34; 95% confidence interval, 3.44-59.06; < 0.001). The mean age of cases with mutations was 38.3 years compared with 46.7 years among other cases without such mutations ( = 0.03).

Conclusions: Our findings replicate the earlier report of a high proportion of mutations in among patients with symptomatic breast cancer in SSA.

Impact: Given the high burden of inherited breast cancer in SSA countries, genetic risk assessment could be integrated into national cancer control plans.
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http://dx.doi.org/10.1158/1055-9965.EPI-19-0506DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7007381PMC
February 2020

Soy intake and breast cancer risk: a prospective study of 300,000 Chinese women and a dose-response meta-analysis.

Eur J Epidemiol 2020 Jun 21;35(6):567-578. Epub 2019 Nov 21.

Department of Epidemiology and Biostatistics, School of Public Health, Peking University Health Science Center, 38 Xueyuan Road, Beijing, 100191, China.

Epidemiological evidence on the association of soy intake with breast cancer risk is still inconsistent due to different soy intake levels across previous studies and small number of breast cancer cases. We aimed to investigate this issue by analyzing data from the China Kadoorie Biobank (CKB) study and conducting a dose-response meta-analysis to integrate existing evidence. The CKB study included over 300,000 women aged 30-79 from 10 regions across China enrolled between 2004 and 2008, and followed-up for breast cancer events until 31 December 2016. Information on soy intake was collected from baseline, two resurveys and twelve 24-h dietary recalls. We also searched for relevant prospective cohort studies to do a dose-response meta-analysis. The mean (SD) soy intake was 9.4 (5.4) mg/day soy isoflavones among CKB women. During 10 years of follow-up, 2289 women developed breast cancers. The multivariable-adjusted relative risk was 1.00 (95% confidence interval [CI] 0.81-1.22) for the fourth (19.1 mg/day) versus the first (4.5 mg/day) soy isoflavone intake quartile. Meta-analysis of prospective studies found that each 10 mg/day increment in soy isoflavone intake was associated with a 3% (95% CI 1-5%) reduced risk of breast cancer. The CKB study demonstrated that moderate soy intake was not associated with breast cancer risk among Chinese women. Higher amount of soy intake might provide reasonable benefits for the prevention of breast cancer.
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http://dx.doi.org/10.1007/s10654-019-00585-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7320952PMC
June 2020

Two truncating variants in FANCC and breast cancer risk.

Sci Rep 2019 08 29;9(1):12524. Epub 2019 Aug 29.

Westmead Institute for Medical Research, University of Sydney, Sydney, New South Wales, Australia.

Fanconi anemia (FA) is a genetically heterogeneous disorder with 22 disease-causing genes reported to date. In some FA genes, monoallelic mutations have been found to be associated with breast cancer risk, while the risk associations of others remain unknown. The gene for FA type C, FANCC, has been proposed as a breast cancer susceptibility gene based on epidemiological and sequencing studies. We used the Oncoarray project to genotype two truncating FANCC variants (p.R185X and p.R548X) in 64,760 breast cancer cases and 49,793 controls of European descent. FANCC mutations were observed in 25 cases (14 with p.R185X, 11 with p.R548X) and 26 controls (18 with p.R185X, 8 with p.R548X). There was no evidence of an association with the risk of breast cancer, neither overall (odds ratio 0.77, 95%CI 0.44-1.33, p = 0.4) nor by histology, hormone receptor status, age or family history. We conclude that the breast cancer risk association of these two FANCC variants, if any, is much smaller than for BRCA1, BRCA2 or PALB2 mutations. If this applies to all truncating variants in FANCC it would suggest there are differences between FA genes in their roles on breast cancer risk and demonstrates the merit of large consortia for clarifying risk associations of rare variants.
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http://dx.doi.org/10.1038/s41598-019-48804-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6715680PMC
August 2019

Hematologic toxicity in BRCA1 and BRCA2 mutation carriers during chemotherapy: A retrospective matched cohort study.

Cancer Med 2019 09 12;8(12):5609-5618. Epub 2019 Aug 12.

Department of Medicine, Center for Clinical Cancer Genetics & Global Health, University of Chicago, Chicago, IL, USA.

Women who inherit a BRCA1 or BRCA2 mutation have an increased risk of breast cancer. Preliminary evidence suggests they may also have defects in bone marrow function. To test this hypothesis, we conducted a multicenter, retrospective, matched cohort study, comparing women with localized breast cancer requiring cytotoxic chemotherapy who carried an inherited BRCA1 or BRCA2 mutation to similar wild-type patients treated between 1995 and 2017 and matched based on age, race, site, and chemotherapy regimen. The proportion who developed specific hematologic toxicities, timing of these toxicities, and patterns of blood count fluctuations over time were compared among BRCA1 carriers vs matched wild-type patients and among BRCA2 carriers vs matched wild-type patients. 88 BRCA1 carriers and 75 BRCA2 carriers were matched to 226 and 242 wild-type patients, respectively. The proportions and timing of experiencing any grade or grade 3/4 cytopenias during chemotherapy were not significantly different for BRCA1 carriers or BRCA2 carriers vs matched wild-type patients. Proportions requiring treatment modifications and time to first modification were also similar. Patterns of blood count fluctuations over time in mutation carriers mirrored those in wild-type patients overall and by the most common regimens. Women with an inherited mutation in BRCA1 or BRCA2 experience similar frequency, severity, and timing of hematologic toxicities during curative intent breast cancer chemotherapy as matched wild-type patients. Our findings suggest that BRCA1 or BRCA2 haploinsufficiency is sufficient for adequate bone marrow reserve in the face of short-term repetitive hematopoietic stressors.
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http://dx.doi.org/10.1002/cam4.2471DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6745828PMC
September 2019

Prenatal Diethylstilbestrol Exposure and Risk of Depression in Women and Men.

Epidemiology 2019 09;30(5):679-686

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

Background: Prenatal exposure to diethylstilbestrol (DES), an endocrine-disrupting chemical, may be associated with depression in adulthood, but previous findings are inconsistent.

Methods: Women (3,888 DES exposed and 1,729 unexposed) and men (1,021 DES exposed and 1,042 unexposed) participating in the National Cancer Institute (NCI) DES Combined Cohort Follow-up Study were queried in 2011 for any history of depression diagnosis or treatment. Hazard ratios (HRs; 95% confidence intervals [CIs]) estimated the associations between prenatal DES exposure and depression risk.

Results: Depression was reported by 993 (26%) exposed and 405 (23%) unexposed women, and 177 (17%) exposed and 181 (17%) unexposed men. Compared with the unexposed, HRs for DES and depression were 1.1 (95% CI = 0.9, 1.2) in women and 1.0 (95% CI = 0.8, 1.2) in men. For medication-treated depression, the HRs (CIs) were 1.1 (0.9, 1.2) in women and 0.9 (0.7, 1.2) in men. In women, the HR (CI) for exposure to a low cumulative DES dose was 1.2 (1.0, 1.4), and for DES exposure before 8 weeks' gestation was 1.2 (1.0, 1.4). In men, the HR for low dose was 1.2 (95% CI = 0.9, 1.6) and there was no association with timing. In women, associations were uninfluenced by the presence of DES-related vaginal epithelial changes or a prior diagnosis of DES-related adverse outcomes.

Conclusions: Prenatal DES exposure was not associated overall with risk of depression in women or men. In women, exposure in early gestation or to a low cumulative dose may be weakly associated with an increased depression risk.
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http://dx.doi.org/10.1097/EDE.0000000000001048DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6679745PMC
September 2019
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