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Prevalence of the UGT1A1*28 promoter 

polymorphism and breast cancer risk among 

African American women in Memphis, TN 
Alana Smith1, Cheryl D. Cropp2,3, Gregory Vidal4,5, Elizabeth Pritchard5, Jennifer Cordero1, Claire Simpson1, 

and Athena Starlard-Davenport1* 

*1Department of Genetics, Genomics and Informatics, University of Tennessee Health Science 

Center, Memphis, TN 38163, USA, 2Integrated Cancer Genomics Division, Translational Genomics 

Research Institute (TGen), Phoenix, AZ, 85004, USA, 3Department of Pharmaceutical, Social and 

Administrative Sciences, McWhorter School of Pharmacy, Samford University, Birmingham, AL, 

35229, USA, 4Division of Hematology/Oncology, Department of Medicine, University of 

Tennessee Health Science Center, Memphis, TN 38163, 5The University of Tennessee West Cancer 

Center; Memphis, TN 38163 

*Corresponding author’s e-mail: astarlar@uthsc.edu 

ABSTRACT 
Inherited variations in UDP-glucuronosyltransferase 1A1 (UGT1A1) are associated with an increased breast 

cancer risk in women of African ancestry. The UGT1A1*28 promoter polymorphism is characterized by the 

presence of 7 TA repeats in the TATA box sequence and results in reduced UGT1A1 gene expression and 

enzymatic activity. In this study, we investigated associations between the UGT1A1*28 polymorphism and 

breast cancer risk among African American (AA) women in Memphis, Tennessee, a city with increased breast 

cancer mortality rates among AA women. Saliva was collected from 352 AA women, including breast cancer 

cases (n=82) and controls (n=270) between June 2016 to June 2017. DNA was isolated and sequenced for 

the UGT1A1*28 polymorphism. The odds ratio for cases with the low UGT1A1 activity alleles (TA)7/8 repeat 

genotypes versus 5/5, 5/6, and 6/6 genotypes was 1.46 [95% CI, 0.65-3.31; P = 0.36] in premenopausal 

women and 1.10 (95% CI, 0.52-2.38; P = 0.79) in postmenopausal women. Further analysis of TCGA RNA-seq 

data showed that UGT1A1 mRNA was significantly lower among estrogen receptor (ER)-negative breast 

cancers from AA as compared to non-Hispanic white women with ER-negative breast cancer. Larger 

epidemiological studies are needed to determine the functional consequence of the UGT1A1*28 

polymorphism on breast cancer risk in AA women. 

KEYWORDS: UGT1A1, UGT1A1*28, breast cancer disparities, African American, Memphis, TN 

Citation: Smith A et al (2019) Prevalence of the UGT1A1*28 promoter polymorphism and breast cancer risk 

among African American women in Memphis, TN. Cancer Health Disparities 3:e1-e12. 

doi:10.9777/chd.2019.1015.



 
 
 
 
 

 

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INTRODUCTION 

Breast cancer is a leading cause of cancer death 

among African American (AA) women (DeSantis et 

al., 2017). African American (AA) women under the 

age of 45 are most likely to develop breast cancer, 

and AA women of all ages are most likely to die 

from breast cancer (DeSantis et al., 2017). Recent 

data showed that AA women in Memphis, 

Tennessee suffer disproportionately from higher 

breast cancer mortality rates compared to non-

Hispanic white women (Hunt et al., 2014; Vidal et 

al., 2017; Whitman et al., 2012). Epidemiological 

evidence highlights the influence of estrogen 

exposures with breast cancer development in 

women of African ancestry (Ambrosone et al., 

2015; Corsini et al., 2017). Established breast cancer 

risk factors, e.g. increased body mass index (BMI), 

obesity, and postmenopausal status (Dietze et al., 

2018; Gerard and Brown, 2018), are thought to 

increase breast cancer risk in women through 

modulation of estrogens. In support of these 

findings, AA women tend to have higher BMI and 

obesity rates compared to non-Hispanic white 

women (Tan et al., 2017). These factors, along with 

genetic variation in key genes involved in estrogen 

conjugation and metabolism, may contribute to 

increased breast cancer risk among AA women. 

A major pathway involved in estrogen conjugation 

and detoxification from circulation is through the 

process of glucuronidation, catalyzed by UDP-

Glucuronosyltransferases (UGTs) (Bock et al., 1987; 

Starlard-Davenport et al., 2007). Human UGT1A1 is 

a major UGT enzyme involved in estrogen 

conjugation (Lepine et al., 2004). Variation in the 

number of thymine-adenine (TA) repeats in the 

TATA-box of the UGT1A1 promoter (rs8175347) 

significantly alters UGT1A1 expression and catalytic 

activity towards estrogens and other compounds 

(Boyd et al., 2006; Iyer et al., 1999). The number of 

TA repeats vary from 5 to 8, with 6 TA repeats 

representing the most common (wild-type) 

number of repeats (Beutler et al., 1998). Individuals 

with more than 6 TA repeats (i.e., 7 TA repeats; 

UGT1A1*28) have markedly reduced enzymatic 

activity, resulting in increased estrogen and 

bilirubin levels, and increased risk for diseases, 

including breast cancer development (Adegoke et 

al., 2004; Guillemette et al., 2001; Huo et al., 2008). 

Studies have shown that the frequency of the low 

activity UGT1A1*28 promoter polymorphism varies 

significantly between ethnic groups, with 

prevalence being highest among populations of 

African descent (Beutler et al., 1998; Guillemette et 

al., 2000; Huo et al., 2008). 

Considering recent reports of higher breast cancer 

mortality rates among AA women in Memphis, TN 

as compared to 49 of the largest US cities (Hunt et 

al., 2014; Vidal et al., 2017), the present study was 

conducted to determine the possible association 

between the UGT1A1 TA repeat polymorphism and 

breast cancer risk in a sample of AA women in 

Memphis, TN. We further explored the relationship 

between UGT1A1 expression and breast cancer risk 

in AA and non-Hispanic white women using RNA 

sequencing data from The Cancer Genome Atlas 

(TCGA). 

MATERIALS AND METHODS 

Study Population 

A total of 352 AA women participants, comprising 

82 breast cancer cases and 270 healthy women 

controls age 18 and older were included in this 

pilot study. Breast cancer patients treated at the 

West Cancer Center (WCC) in Memphis, TN were 

recruited. Normal healthy controls and cancer 

survivors were also recruited at local community 

outreach events in Memphis, TN between June 



 
 
 
 
 

 

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2016 and June 2017. All recruited breast cancer 

patients in this study were either being treated for 

breast cancer or had a prior diagnosis of breast 

cancer. The control group included healthy 

volunteers without a prior diagnosis of breast 

cancer and who were recruited at community 

outreach events. All recruited participants 

completed a 3-page health questionnaire that 

included information on participants’ reproductive 

history, diet and lifestyle factors, and family history 

of cancer. Race was classified according to self-

report. A 2 mL saliva sample was also collected 

using Oragene® OG-500 DNA Self-Collection Kit 

(Ottawa, Ontario, Canada) at the same time the 

participants completed the health questionnaire. 

Ethics 

Written informed consent was obtained from each 

study participant and the study protocol (protocol 

# 16-04551-XP and 16-04502-XP) was approved 

by the Institutional Review Board of the University 

of Tennessee Health Science Center, Memphis, TN 

and was carried out in accordance with the 

guidelines of the Declaration of Helsinki. 

UGT1A1 Promoter Genotyping Analysis. DNA was 

isolated from saliva using DNA Genotek’s Prep-It 

L2P DNA isolation kit (Ottawa, Ontario, Canada). 

DNA was purified using a ZymoResearch DNA 

clean and concentrator kit (Irvine, California). The 

UGT1A1*28 polymorphism was identified from 

DNA that was PCR amplified as previously 

described (Massacesi et al., 2006). Briefly, 

polymerase chain reactions (PCR) were conducted 

in a total volume of 50 μL containing 100 ng of 

genomic DNA, 25 pmoles of the UGT1A1 primer 

(UGT1A1 forward: 5’-GAT TTG AGT ATG AAA TTC 

CAG CCA G-3’ and UGT1A1 reverse: 5′-CCA GTG 

GCT GCC ATC CAC T-3′) (Massacesi et al., 2006) 

and the following reagents (Promega, Madison, 

WI): 0.1 mM each of dCTP, dGTP, dATP and dTTP; 

2.5 mM of MgCl2; 50 mM of potassium chloride; 

10 mM of Tris (pH 9.0); 0.1 % Triton-X; and 2.5 U of 

Taq polymerase. After 35 cycles of amplification 

(denaturation at 94 °C for 30 sec, annealing at 60 

°C for 1 min, and extension at 72 °C for 1 min), the 

amplification products were electrophoresed in 3% 

agarose gel and visualized after staining with 

ethidium bromide. 

Genotypes of the A(TA)6-8TAA polymorphism 

were determined by bidirectional sequencing with 

forward or reverse primers. PCR products were 

purified using the Qiagen DNA Purification Kit 

(Valencia, CA). DNA sequencing of the UGT1A1 

product (351 bp) containing the polymorphic TA 

repeats was performed using the Sanger method 

employing Applied Biosystems Big Dye v3.1 

Reaction Mix at 1/10X strength combined with an 

appropriate amount of PCR product and 5 pmol 

of the relevant primer. All sequencing data was 

generated in the Molecular Resource Center 

(MRC) of Excellence at The University of Tennessee 

Health Science Center, Memphis, TN. All PCR 

protocols and template/primer ratios were those 

suggested by the manufacturer. The ThermoFisher 

(Applied Biosystems) BDXterminator system was 

used to remove salts, primers and unincorporated 

nucleotides from the labeling reaction. Labelled 

samples were analyzed with an Applied Biosystems 

3130xL Genetic Analyzer using Sequencing 

Analysis v5.2.0 software employing the KB.bcp 

program using the KB_3130_POP7_BDTv3 mobility 

file. All electropherograms were visually examined 

in the MRC to ensure the highest data quality. 

Sample quality was determined prior to dNTP 

incorporation by assaying the A260, A280 and 

A230 values using a Nanodrop 

Spectrophotometer: the preferred A260/A280 and 



 
 
 
 
 

 

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A260/A230 ratios were 1.7 or better. UGT1A1 

genotypes were assigned based on the number of 

TA repeats for each allele (i.e., 6/6, 6/7, 7/7, or 

7/8). The percentage of samples with successful 

calls was ≥98%. 

RNA sequencing analysis. RNA sequencing analysis 

was done with Cufflinks (Trapnell et al., 2013). This 

algorithm reports changes at the transcript and 

gene level as fragment reads per kilobase of exon 

per million reads mapped (FPKM) values. Breast 

carcinoma RNA-Seq data, made available by 

Nationwide’s Children, was queried through the 

National Cancer Institute GCD Data Portal using 

the following criteria: female, 18-90 years old at 

age of diagnosis, alive or dead, African American 

or European American, and not Hispanic. The raw 

FPKM values from this RNA-Seq data were used 

for the analysis. No differential gene expression 

analysis, Cuffdiff, was performed and thus no log2 

(Fold Change) values were obtained. The raw 

FPKM values from Cufflinks were converted to log 

scale for graphing purposes. 

Statistical Analysis 

Demographic characteristics and selected risk 

factors for breast cancer were compared between 

cases and controls using T-tests for continuous 

variables and Chi-square tests for categorical data. 

Data were expressed as the mean ± standard 

deviation. ORs and 95% CIs for breast cancer were 

calculated from unconditional logistic regression 

models and used to estimate relative risk. To 

estimate the allele frequencies, data were analyzed 

using χ2 analysis and two-tailed Fisher’s exact test. 

The observed genotype frequencies of UGT1A1 

were compared with the expected frequencies, 

according to the Hardy-Weinberg equation. A p-

value of <0.05 was considered statistically 

significant. All statistical analyses were performed 

using GraphPad Prism, version 7 software (La Jolla, 

CA). 

RESULTS 

Participant characteristics 

This study was conducted on a total of 352 AA 

women participants, consisting of 82 breast cancer 

cases and 270 healthy women volunteers (Table 1). 

The mean ± SD age of the breast cancer cases 

and the comparison group was 54.5 ± 13.8 and 

48.2 ± 13.8 years, respectively. The minimum and 

maximum age among breast cancer cases was 20 

and 88 years. The minimum and maximum age 

among healthy volunteers was 18 and 79 years. As 

can be seen from Table 1, the group of breast 

cancer patients was matched to the control group 

on age (p > 0.05). There was no significant 

difference between cases and controls for body 

mass index (BMI), smoking status, alcohol 

consumption, family history of cancer or 

menopausal status. The majority of participants, 

both cases and controls, in the cohort had a BMI 

greater than 30, did not smoke, had a family 

history of breast cancer, or were postmenopausal. 

Specifically, more than 90% of cases and 89% of 

controls reported that they do not smoke. 

However, more than 73% of breast cancer cases 

reported that they do not consume alcoholic 

beverages while greater than 52% of healthy 

volunteers reported that they do consume alcohol. 

Overall, no differences were found between the 

groups regarding the characteristics shown in 

Table 1. 

 

Table 1. Characteristics of study participants. 



 
 
 
 
 

 

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Characteristic Cases (n = 82) 
a
 Controls (n = 270)  p-value 

Age in years, mean  SD  54.5  13.8 48.2  13.8 0.170 

   Minimum  20.0 18.0  

   25% Percentile  44.0 38.0  

   Median  52.5 50.0  

   75% Percentile  64.3 58.0  

   Maximum  88.0 79.0  

Body Mass Index (BMI), n (%) 0.920 

  Optimal, BMI 18.5 – 25 17 (20.7) 47 (17.4)  

  Overweight, BMI 25-30 21 (25.6) 75 (27.8)  

  Obese, BMI > 30  43 (52.4) 146 (54.1)  

   Missing 1 2  

Smoking status, n (%) 0.886 

   Yes 3 (3.66) 23 (8.52)  

   No 79 (96.3) 241 (89.3)  

   Missing 0 6  

Alcohol consumption, n (%) 0.965 

   Yes 22 (26.8) 141 (52.2)  

   No 60 (73.2) 121 (44.8)  

   Missing 0 8  

Family history of cancer, n (%)                                                                     0.958 

   Yes 52 (63.4) 141 (52.2)  

   No 29 (35.4) 122 (45.2)  

   Missing 1 5  

Menopause Status, n (%) >0.999 

    Pre-menopausal 36 (43.9) 132 (48.9)  

    Post-menopausal 46 (56.1) 138 (51.1)  

 

Distribution of UGT1A1 allele and genotype 

frequencies in our study population 

Results of genotyping analysis for the UGT1A1 

promoter TATA box variants among breast cancer 

cases and controls in our study population are 

presented in Table 2. The number of (TA) repeats 

in the UGT1A1 promoter TATA box included 5TA, 

6TA, 7TA and 8TA. The normal or wild-type allele 

is characterized by 6 TA repeats, while 5TA, 7TA, 

and 8TA repeats are variants. The polymorphism 

with the highest allele frequency among breast 

cancer cases was 7TA (UGT1A1*28) at 43%. 

However, among controls the normal or wild-type 

allele, consisting of 6TA, was most common at 

47%. The allele frequency of the UGT1A1*36 (5TA) 

and UGT1A1*37 (8TA) was least common among 

both breast cancer cases and controls. 

Table 2 also shows the UGT1A1 (TA) genotype 

frequencies. The 7/7 homozygous genotype of the 

UGT1A1 gene (UGT1A1*28) was identified in 17.8 % 

of breast cancer cases and 17.1% of controls. The 

6/7 heterozygous genotype was the most 

prevalent in both breast cancer cases (35.6%) and 

controls (34.1%). There was no departure from 

Hardy-Weinberg equilibrium and no significant 



 
 
 
 
 

 

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association in allele and genotype frequencies 

between cases and controls (χ2 test, p>0.05). The 

frequency distribution of the UGT1A1 promoter 

variants in our population and the DNA sequence 

lengths of the promoter variants are shown in 

supplementary Figure 1. 

Table 2.  UGT1A1 promoter allele and genotype frequencies of study population. 

Allele 
a
 Cases 

b
 Controls 

b
 p-value 

5 0.07 0.10 0.33 

6 0.42 0.47  

7 0.43 0.40  

8 0.08 0.03  

Genotype 
c
 Cases, n (%) 

d
 Controls, n (%) 

d
  

5/5 4 (5.48) 7 (2.78) 0.63 

5/6 2 (2.74) 17 (6.75)  

6/6 17 (23.3) 68 (27.0)  

6/7 26 (35.6) 86 (34.1)  

7/7 13 (17.8) 43 (17.1)  

7/8 7 (15.1) 31 (12.3)  

8/8 0 (0) 0 (0)  

 

Adapted from Guillemette et al, 2000 (Guillemette et al., 2001) 

a 2 test comparing distribution in cases versus controls for trend: p = 0.33 

b Number of alleles/number of chromosomes (unweighted) 

c 2 test comparing distribution in cases versus controls for trend: p = 0.63 

d Number of participants with genotype/total participants (unweighted) 

Association between UGT1A1 genotypes and 

obesity and menopausal status 

We further determined the effect of UGT1A1 

genotypes on menopausal status and obesity 

status using odds ratios (ORs) (Table 3). 

Participants were divided into two categories 

based on UGT1A1 promoter activity. Participants 

with high UGT1A1 (TA) activity alleles carried 5/5, 

5/6, and 6/6 TA repeats and those considered to 

have low activity alleles had the presence of 6/7, 

7/7 or 7/8 TA repeats. All comparisons were 

achieved with the reference group including 5 or 6 

allele-containing genotypes (5/5, 5/6, and 6/6). On 

stratification by menopausal status, association 

between UGT1A1 high-risk genotypes and risk of 

breast cancer showed an OR of 1.46 in 

premenopausal women (95% CI, 0.65-3.31; P = 

0.361) and an OR of 1.10 in postmenopausal 

women (95% CI, 0.52-2.38; P = 0.793). Although 

not significant, overweight and obese status 

among women with the low activity 7/8 TA repeat 

alleles had a 92% increased risk of breast cancer 

compared to wild-type (5TA) and high activity 

(6TA) alleles. 

 

 



 
 
 
 
 

 

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Table 3. UGT1A1 genotypes and risk of breast cancer by menopause and obesity status. 

Genotypes Cases, n (%) Controls, n (%) OR (95% CI) p-value 

Premenopausal women 

   5/5, 5/6, 6/6 10 (27.8) 45 (36.0) 1.46 (0.65-3.31) 0.361 

  6/7, 7/7, 7/8 26 (72.2) 80 (64.0)   

Postmenopausal women 

   5/5, 5/6, 6/6 13 (35.1) 48 (37.5)  1.10 (0.52-2.38) 0.793 

  6/7, 7/7, 7/8 24 (64.9) 80 (62.5)   

Optimal weight 

  5/5, 5/6, 6/6                        6 (40.0)                  14 (34.1) 0.78 (0.23-2.63) 0.686 

 6/7, 7/7, 7/8                         27 (65.9)   

Overweight/Obese 

 5/5, 5/6, 6/6                       12 (24.0) 75 (37.7) 1.92 (0.94-3.89) 0.073 

6/7, 7/7, 7/8                        38 (76.0) 124 (62.3)   

 

Investigation of UGT1A1 mRNA expression in 

breast tumor tissues from AA and non-Hispanic 

white women in the TCGA 

We previously showed that UGT1A1 mRNA levels 

was significantly lower in breast tumors as 

compared to normal breast tissues from AA and 

non-Hispanic white women (Starlard-Davenport et 

al., 2012). We demonstrated that low UGT1A1 

mRNA expression in breast tumors correlated with 

UGT1A1*28 low activity alleles. Guillemette et al 

also showed that the UGT1A1*28 was associated 

with Estrogen Receptor (ER)-breast cancers in 

premenopausal AA women (Guillemette et al., 

2000). Therefore, we explored The Cancer 

Genome Atlas (TCGA), a comprehensive database 

that catalogues genomic alterations responsible 

for cancer from 500 patients, to determine 

whether UGT1A1 RNA expression was altered in a 

group of human breast cancer samples from AA (n 

= 94) and non-Hispanic white (n = 244) women by 

estrogen receptor (ER) status. TCGA RNA-

sequencing data and the log2 (average raw FPKM) 

value was plotted per UGT1A1 gene for AA tumor 

and non-Hispanic white tumor samples by ER 

status (Figure 1). We observed that UGT1A1 mRNA 

expression was lower in breast tumors from AA as 

compared to non-Hispanic white women although 

not significant (Figure 1). We further showed that 

UGT1A1 gene expression was significantly higher in 

ER negative breast tumors from non-Hispanic 

white women as compared to AA women with ER 

negative and ER positive breast tumors. 

 

Figure 1. UGT1A1 RNA expression from TCGA 

database.   The log2(average raw FPKM) value is 

plotted per UGT1A1 gene expression for AA tumor 

and non-Hispanic white tumor samples by 

Estrogen Receptor (ER) status. The average raw 

FPKM values for UGT1A1 were zero or close to 

zero. 

DISCUSSION 



 
 
 
 
 

 

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In the present study, we investigated the 

associations between the UGT1A1*28 TA repeat 

polymorphism located in the promoter region of 

UGT1A1 among AA breast cancer cases and 

healthy AA women volunteers. Our study is the 

first to investigate the association between the 

UGT1A1*28 polymorphism and breast cancer risk 

among women in Memphis, TN, a city with one of 

the highest breast cancer mortality disparity rates 

among AA women compared to non-Hispanic 

white women in the US. 

The human UGT1A1 gene is a member of the 

UGT1A subfamily of enzymes that are encoded by 

the UGT1A gene locus on chromosome 2q37.1. 

The UGT1A isoforms share 4 common exons from 

exon 2 to exon 5 and have a unique exon 1 and 

individual promoter pairs (Tukey and Strassburg, 

2000). UGT1A1 is the most abundant member of 

the UGT1A family in human liver and is also the 

major isoform responsible for the metabolism and 

clearance of many endogenous and exogenous 

compounds, including β-estradiol and its 

metabolites (Lepine et al., 2004). It is well known 

that prolonged exposure to β-estradiol is a major 

risk factor for breast cancer development in 

women. Elevated levels of circulating estrogens are 

associated with increased breast cancer risk in 

postmenopausal women. The carcinogenic 

potential of estrogens is not only mediated by 

estrogen receptor signaling but also mediated by 

increased cellular oxidative metabolism of 

estrogens to genotoxic estrogen metabolites 

(Cavalieri et al., 1997). 

Several studies have investigated the impact of 

inherited genetic variations in UGT1A1 on the 

incidence risk of various cancers including breast 

cancer (Adegoke et al., 2004; Guillemette et al., 

2000; Huo et al., 2008; Shatalova et al., 2006). The 

scientific premise for the association of UGT1A1 

genetic variants and breast cancer risk stems from 

the hypothesis that reduced UGT1A1 estrogen 

conjugating activity results in decreased cellular 

oxidative estrogen metabolism and increased 

estrogen bioavailability in circulation. The most 

studied UGT1A1 polymorphism is UGT1A1*28 

(rs8175347) polymorphism is characterized by an 

extra TA repeat (TA-7) in the TATA box region in 

the UGT1A1 promoter resulting in decreased gene 

transcription and glucuronidation activity (Beutler 

et al., 1998). UGT1A1*28 has been previously linked 

to increased risk of breast cancer. For instance, a 

study by Guillemette et al showed for the first time 

that 200 premenopausal AA women with ER 

negative breast cancer have a higher prevalence 

of low UGT1A1 activity allele-containing genotypes 

than 200 female controls of African ancestry 

(Guillemette et al., 2000). Although a limitation of 

our genetic study was the small population sample 

size and lack of information regarding hormone 

receptor breast tumor status among breast cancer 

patients, we still observed the low activity 

UGT1A1*28 polymorphism among premenopausal 

AA women with breast cancer but not in 

postmenopausal AA breast cancer patients, which 

is in agreement with findings previously reported 

(Guillemette et al., 2000). Additionally, in our study, 

the gene frequency of all UGT1A1 alleles in African 

American women was similar to those reported 

previously by Guillemette et al (Guillemette et al., 

2000). A similar study was conducted on women in 

the Shanghai Breast Cancer Study, a population-

based case-control study that found similar results 

(Adegoke et al., 2004). In that study, Adegoke et al 

also found that women under the age of 40 who 

carried the UGT1A1*28 risk allele had an increased 

risk of breast cancer with an OR = 1.7; 95% CI = 

1.0-2.7) but not among women 40 years old and 



 
 
 
 
 

 

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over (OR = 0.8; 0.7-1.1) (Adegoke et al., 2004). 

Likewise, similar findings have been found in 

Russian women (Shatalova et al., 2006). By 

contrast, Huo et al genotyped DNA for the 

UGT1A1*28 polymorphism among 512 Nigerian 

breast cancer cases and 226 community controls 

and found that premenopausal indigenous 

Nigerian African women with the low-activity 

UGT1A1 TA repeat alleles were protected against 

breast cancer (Huo et al., 2008). These findings 

show that the frequency of the UGT1A1*28 

polymorphism varies between populations by race 

and ethnicity. 

In our previous published study, we showed that 

the UGT1A1*28 promoter polymorphism was 

associated with decreased UGT1A1 gene 

expression in AA and non-Hispanic white women 

with breast cancer (Starlard-Davenport et al., 

2012). In that study, we observed a significant 

decrease in UGT1A1 mRNA expression levels 

among breast tissues isolated from AA and non-

Hispanic white women with breast cancer (N = 17) 

and normal healthy controls (N = 30) (p = 0.02). 

Based on these findings and those of Guillemette 

et al (Guillemette et al., 2000) who found an 

association between the UGT1A1*28 polymorphism 

and ER negative breast cancer risk in AA women, 

we interrogated existing TCGA RNA sequencing 

datasets to determine whether UGT1A1 gene 

expression was differentially expressed among AA 

and non-Hispanic white breast cancer patients by 

ER status. In our analysis, we were unable to 

compare UGT1A1 mRNA expression between AA 

breast cancer cases and AA healthy controls since 

there was only one healthy control available for 

comparison. Thus, it was impossible to conduct 

statistical analysis of UGT1A1 mRNA between 

normal and breast cancer AA patients in the 

TCGA. However, further analysis of UGT1A1 mRNA 

expression in the TCGA database between AA 

breast cancers and non-Hispanic white breast 

cancer cases showed that UGT1A1 expression was 

downregulated in breast cancers and was lower 

among AA breast cancers compared to non-

Hispanic white breast cancer cases, especially 

among ER negative breast tumors from AA 

women. 

In conclusion, this genetic study supports previous 

findings highlighting the association between the 

UGT1A1*28 polymorphism and premenopausal 

breast cancer risk among AA women. This study 

also highlights the importance of investigating 

genetic studies in an underserved minority AA 

population such as Memphis, TN where the breast 

cancer mortality rates is significantly higher among 

AA women compared to non-Hispanic white 

women. Larger epidemiological studies are 

required to replicate these findings in other 

populations of African ancestry and to delineate 

the exact biological mechanisms underlying the 

effects of the UGT1A1*28 promoter polymorphism 

in AA women. 

Acknowledgements 

The authors wish to thank all participants in this 

study and volunteers who assisted in consenting 

and collecting biospecimens. Special thanks to 

Mrs. Gwendolyn Brown with the Carin and Sharin 

Breast Cancer Support Group and Dr. Osborne 

Burks at Southwest Tennessee Community 

College. The authors wish to acknowledge support 

from the University of Tennessee Health Science 

Center (UTHSC) Molecular Resource Center and 

the West Cancer Center. 

 

Funding Sources 

This work was supported by generous funds from 

the UTHSC Center for Integrative Genetics (CITG) 

and Methodist Mission to AS-D). 



 
 
 
 
 

 

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Conflict of interest 
The authors declare that no competing or conflict of 

interests exists. The funders had no role in study 

design, writing of the manuscript, or decision to 

publish. 

Authors’ contributions 
Conceptualization: AS-D, Formal analysis: AS-D, 

CDC, CS.   Methodology:  AS,  JC, GV, EP. 

Supervision: AS-D. Writing ± original draft: AS-D, AS, 

CDC, GV. Writing  ±  review  &  editing:  AS-D, AS, 

CDC, GV, CS  

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Supplemental Figure 1 


