Case-control study of fetal microchimerism and breast cancer.
BACKGROUND
Prior pregnancy is known to protect against development of breast cancer. Recent studies have demonstrated that pregnancy has the capacity to establish small numbers of immunologically active fetal-derived cells in the mother, a phenomenon known as fetal microchimerism (FMc). We asked whether presence of FMc, routinely acquired during pregnancy, is a protective factor for breast cancer.


RESULTS
DNA extracts from peripheral blood specimens were obtained from a population-based case-control study of risk factors for breast cancer in women 21 to 45 years old. Specimens were tested with quantitative PCR for presence and concentrations of male DNA presumed to derive from prior pregnancies with a male fetus. Odds ratios (OR) and 95% confidence intervals (CI) were estimated with consideration of multiple established reproductive and environmental risk factors for breast cancer. FMc results were generated on 99 parous women, 54 with primary invasive breast cancer and 45 general population controls. FMc prevalence was 56% (25/45) and 26% (14/54) in controls and cases, respectively. Women harboring FMc were less likely to have had breast cancer (OR = 0.29, 95% CI 0.11-0.83; p = 0.02, adjusting for age, number of children, birth of a son, history of miscarriage, and total DNA tested). In addition, FMc concentrations were higher in controls versus cases (p = 0.01). Median concentrations were 2 (0-78) and 0 (0-374) fetal genomes/10(6) maternal genomes in controls and cases, respectively.


CONCLUSIONS
Results suggest that the enigma of why some parous women are not afforded protection from breast cancer by pregnancy might in part be explained by differences in FMc. Mechanistic studies of FMc-derived protection against breast cancer are warranted.
Gadi
Vijayakrishna K
VK
Division of Clinical Research, Fred Hutchinson Cancer Research Center, Seattle, Washington, USA. vkgadi@u.washington.edu
Malone
Kathleen E
KE
Guthrie
Katherine A
KA
Porter
Peggy L
PL
Nelson
J Lee
JL
D000328:Adult; D001943:Breast Neoplasms / Q000453:epidemiology / Q000209:etiology* / Q000473:pathology; D016022:Case-Control Studies; D046528:Chimerism; D004273:DNA, Neoplasm / Q000235:genetics / Q000378:metabolism; D005260:Female; D005333:Fetus / Q000166:cytology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009361:Neoplasm Invasiveness / Q000473:pathology; D016133:Polymerase Chain Reaction; D011247:Pregnancy; D011379:Prognosis; D012307:Risk Factors
D004273:DNA, Neoplasm