Estrogen receptor/progesterone receptor-negative breast cancers of young African-American women have a higher frequency of methylation of multiple genes than those of Caucasian women.
OBJECTIVE
To provide a molecular rationale for negative prognostic factors more prevalent in African-American (AA) than Caucasian (Cau) women, we investigated the frequency of promoter hypermethylation in invasive ductal breast cancers in the two races.


METHODS
HIN-1, Twist, Cyclin D2, RAR-beta, and RASSF1A were analyzed in DNA from 67 AA and 44 Cau invasive ductal breast cancers, stratified by age and estrogen receptor/progesterone receptor (ER/PR) status, by methylation-specific PCR. Hierarchical multiple logistic regression analysis was applied to determine estimated probabilities of methylation. Expression of HIN-1 mRNA was analyzed by in situ hybridization and quantitative reverse transcribed PCR.


RESULTS
Significant differences between races were observed in the ER-/PR-, age < 50 subgroup; AA tumors had higher frequency of methylation (P < 0.001) in four of five genes as compared with Cau and also a higher prevalence (80 versus 0%; P < 0.005) of three or more methylated genes per tumor. No differences in gene methylation patterns were observed across the two races for ER+/PR+ tumors in all ages and ER-/PR- tumors in age > 50. ER+/PR+ status was associated with higher frequency of methylation in Cau tumors of all ages but only with the age > 50 subgroup in AA. Frequent Cyclin D2 methylation was significantly associated (P = 0.01) with shorter survival time.


CONCLUSIONS
ER-/PR-, age < 50 tumors in AA women, have a significantly higher frequency of hypermethylation than in those of Cau women. Comparative studies, such as these, could provide a molecular basis for differences in tumor progression and pathology seen in the two races.
Mehrotra
Jyoti
J
Breast Cancer Program, Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, Maryland, USA.
Ganpat
M Michelle
MM
Kanaan
Yasmine
Y
Fackler
Mary Jo
MJ
McVeigh
Megan
M
Lahti-Domenici
Jaana
J
Polyak
Kornelia
K
Argani
Pedram
P
Naab
Tammy
T
Garrett
Elizabeth
E
Parmigiani
Giovanni
G
Broome
Carolyn
C
Sukumar
Saraswati
S
D044383:Black People / Q000235:genetics*; D001943:Breast Neoplasms / Q000453:epidemiology / Q000235:genetics / Q000473:pathology*; D019175:DNA Methylation; D004273:DNA, Neoplasm / Q000235:genetics*; D005260:Female; D006801:Humans; D008875:Middle Aged; D016133:Polymerase Chain Reaction / Q000379:methods; D015995:Prevalence; D011960:Receptors, Estrogen / Q000235:genetics*; D011980:Receptors, Progesterone / Q000235:genetics*; D012044:Regression Analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014481:United States / Q000453:epidemiology; D044465:White People / Q000235:genetics*; D001741:Black or African American
D004273:DNA, Neoplasm; D011960:Receptors, Estrogen; D011980:Receptors, Progesterone