Methyl-group dietary intake and risk of breast cancer among African-American women: a case-control study by methylation status of the estrogen receptor alpha genes.
OBJECTIVE
Recent molecular studies show that the absence of estrogen receptor (ER) alpha gene expression in breast cancer is associated with methylation of the CpG island located in the 5' region and the first exon of the ER alpha gene. Because CpG island methylation is an early event in carcinogenesis and because a methyl-deficient diet may lead to abnormal DNA methylation including CpG island methylation, we hypothesized that a methyl-deficient diet is more likely to be associated with breast cancer with methylated ER alpha gene CpG islands. This study aimed to test this hypothesis in African-American women using a case-control design.


METHODS
Cases were 304 African-American women pathologically diagnosed with breast cancer during 1995-1998 who lived in three Tennessee counties. Controls were 305 African-American women without breast cancer, who were selected through random-digit dialing and frequency matched to cases by 5-year age range and county of residence. Information on dietary intake and other risk factors was collected through telephone interviews. Dietary methyl-components were defined based on folate and methionine intakes and alcohol consumption. Tumor tissue samples were collected for measuring methylation status of the ER alpha gene.


RESULTS
Our results showed that the odds ratio (OR) estimates for lower dietary folate intake were 2.0 (95% confidence interval, CI: 0.8-4.8) for cases with a methylated ER alpha gene, 0.6 (95% CI: 0.3-1.5) for cases with an unmethylated ER alpha gene, and 1.6 (95% CI: 0.7-3.8) for cases with unknown methylation status (presumably including cases with both methylated and un-methylated genes). However, low methionine intake appeared more likely to be associated with tumors with unknown methylation status and high level of alcohol consumption seemed more likely to be related to tumors with un-methylated genes.


CONCLUSIONS
These results did not show a pattern consistent with the study hypothesis that methyl-deficient diets are more likely related to breast cancer with a methylated ER gene.
Zhu
Kangmin
K
United States Military Cancer Institute, Walter Reed Army Medical Center, Washington, DC 20307, USA. Kangmin.zhu@na.amedd.army.mil
Davidson
Nancy E
NE
Hunter
Sandra
S
Yang
Xiaowei
X
Payne-Wilks
Kathleen
K
Roland
Chanel L
CL
Phillips
Dawn
D
Bentley
Christy
C
Dai
Min
M
Williams
Scott M
SM
D000328:Adult; D001741:Black or African American / Q000235:genetics*; D001943:Breast Neoplasms / Q000453:epidemiology / Q000208:ethnology* / Q000235:genetics; D016022:Case-Control Studies; D019175:DNA Methylation; D005247:Feeding Behavior / Q000208:ethnology* / Q000502:physiology; D005260:Female; D005494:Folic Acid Deficiency / Q000235:genetics / Q000378:metabolism; D006801:Humans; D008715:Methionine / Q000172:deficiency* / Q000235:genetics / Q000378:metabolism; D008875:Middle Aged; D011960:Receptors, Estrogen / Q000235:genetics* / Q000378:metabolism; D012307:Risk Factors; D011795:Surveys and Questionnaires; D013714:Tennessee / Q000453:epidemiology
D011960:Receptors, Estrogen; D008715:Methionine