Body mass, polymorphisms in obesity-related genes, and the risk of developing breast cancer among women with benign breast disease.
BACKGROUND
A cohort study was conducted among post-menopausal women to determine whether genetic polymorphisms in selected obesity-related genes (PPARG, LPL, LEPR, PON1, PON2, TNF-alpha) were associated with the progression of benign breast disease (BBD) to breast cancer and whether the selected polymorphisms modified the association between body mass and breast cancer among women with BBD.


METHODS
Among participants in an ongoing cohort study, 994 Caucasian post-menopausal women had a breast biopsy for BBD. Of these women, 61 subsequently developed breast cancer. A short questionnaire was administered at baseline in 1989. Genotypes were determined using DNA extracted from blood collected in 1989.


RESULTS
In this cohort, body mass index (BMI) was positively associated with the risk of developing breast cancer. In contrast, polymorphisms in PON1 (Gln192Arg) and LEPR (IVS2+6920) were associated with a decreased risk of developing invasive breast cancer. No statistically significant associations were observed for polymorphisms in PPARG, PON2, LPL, or TNF and breast cancer risk or for interactions between the polymorphisms and BMI and breast cancer risk.


CONCLUSIONS
The findings suggest that specific polymorphisms in the PON1 and LEPR genes may play a role in progression of BBD to breast cancer among post-menopausal Caucasian women.
Gallicchio
Lisa
L
Prevention and Research Center, The Weinberg Center for Women's Health and Medicine, Mercy Medical Center, 227 St. Paul Place, Baltimore, MD 21202, USA. lgallic@mdmercy.com
McSorley
Meghan A
MA
Newschaffer
Craig J
CJ
Huang
Han-Yao
HY
Thuita
Lucy W
LW
Hoffman
Sandra C
SC
Helzlsouer
Kathy J
KJ
D043303:Aryldialkylphosphatase / Q000235:genetics; D014408:Biomarkers, Tumor / Q000235:genetics*; D001835:Body Weight; D001941:Breast Diseases / Q000235:genetics*; D001943:Breast Neoplasms / Q000235:genetics*; D015331:Cohort Studies; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000235:genetics*; D009765:Obesity / Q000235:genetics*; D047495:PPAR gamma / Q000235:genetics; D020641:Polymorphism, Single Nucleotide; D017698:Postmenopause; D011956:Receptors, Cell Surface / Q000235:genetics; D054411:Receptors, Leptin; D012307:Risk Factors; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics
D014408:Biomarkers, Tumor; D009363:Neoplasm Proteins; D047495:PPAR gamma; D011956:Receptors, Cell Surface; D054411:Receptors, Leptin; D014409:Tumor Necrosis Factor-alpha; D043303:Aryldialkylphosphatase; C468406:PON1 protein, human; C468411:PON2 protein, human