Global methylation levels in peripheral blood leukocyte DNA by LUMA and breast cancer: a case-control study in Japanese women.
BACKGROUND
Global hypomethylation has been suggested to cause genomic instability and lead to an increased risk of cancer. We examined the association between the global methylation level of peripheral blood leukocyte DNA and breast cancer among Japanese women.


METHODS
We conducted a hospital-based case-control study of 384 patients aged 20-74 years with newly diagnosed, histologically confirmed invasive breast cancer, and 384 matched controls from medical checkup examinees in Nagano, Japan. Global methylation levels in leukocyte DNA were measured by LUminometric Methylation Assay. Odds ratios (ORs) and 95% confidence intervals (CIs) for the associations between global hypomethylation and breast cancer were estimated using a logistic regression model.


RESULTS
Compared with women in the highest tertile of global methylation level, ORs for the second and lowest tertiles were 1.87 (95% CI=1.20-2.91) and 2.86 (95% CI=1.85-4.44), respectively. Global methylation levels were significantly lower in cases than controls, regardless of the hormone receptor status of the cancer (all P values for trend <0.05).


CONCLUSIONS
These findings suggest that the global methylation level of peripheral blood leukocyte DNA is low in patients with breast cancer and may be a potential biomarker for breast cancer risk.
1] Division of Genetics, National Cancer Center Research Institute, 5-1-1 Tsukiji, Tokyo 104-0045, Japan [2] Department of Biostatistics, National Cancer Center, 5-1-1 Tsukiji, Tokyo 104-0045, Japan.
A
A
Kuchiba
Division of Epidemiology and Prevention, Research Center for Cancer Prevention and Screening, National Cancer Center, 5-1-1 Tsukiji, Tokyo 104-0045, Japan.
M
M
Iwasaki
Division of Genetics, National Cancer Center Research Institute, 5-1-1 Tsukiji, Tokyo 104-0045, Japan.
H
H
Ono
Department of Surgery, Nagano Matsushiro General Hospital, 183 Matsushiro, Matsushiro-machi, Nagano 381-1231, Japan.
Y
Y
Kasuga
Department of Breast and Thyroid Surgery, Nagano Red Cross Hospital, 5-22-1 Wakasato, Nagano 380-8582, Japan.
S
S
Yokoyama
Department of Breast and Thyroid Surgery, Nagano Red Cross Hospital, 5-22-1 Wakasato, Nagano 380-8582, Japan.
H
H
Onuma
Department of Surgery, Nagano Municipal Hospital, 1333-1 Tomitake, Nagano 381-8551, Japan.
H
H
Nishimura
Department of Surgery, Nagano Hokushin General Hospital, 1-5-63 Nishi, Nagano 383-8505, Japan.
R
R
Kusama
Division of Epidemiology and Prevention, Research Center for Cancer Prevention and Screening, National Cancer Center, 5-1-1 Tsukiji, Tokyo 104-0045, Japan.
S
S
Tsugane
Division of Genetics, National Cancer Center Research Institute, 5-1-1 Tsukiji, Tokyo 104-0045, Japan.
T
T
Yoshida
D000328:Adult; D000368:Aged; D001943:Breast Neoplasms / Q000235:genetics* / Q000473:pathology; D018270:Carcinoma, Ductal, Breast / Q000235:genetics* / Q000473:pathology; D016022:Case-Control Studies; D018899:CpG Islands; D019175:DNA Methylation; D005260:Female; D006801:Humans; D007564:Japan; D007963:Leukocytes, Mononuclear / Q000378:metabolism*; D008875:Middle Aged; D025202:Molecular Diagnostic Techniques; D020641:Polymorphism, Single Nucleotide; D012306:Risk; D055815:Young Adult