Gallicchio Lisa, McSorley Meghan A, Newschaffer Craig J, Huang Han-Yao, Thuita Lucy W, Hoffman Sandra C, Helzlsouer Kathy J
Prevention and Research Center, The Weinberg Center for Women's Health and Medicine, Mercy Medical Center, 227 St. Paul Place, Baltimore, MD 21202, USA.
Cancer Detect Prev. 2007;31(2):95-101. doi: 10.1016/j.cdp.2007.02.004. Epub 2007 Apr 10.
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.
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.
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.
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.
对绝经后女性进行了一项队列研究，以确定所选肥胖相关基因（PPARG、LPL、LEPR、PON1、PON2、TNF-α）的基因多态性是否与良性乳腺疾病（BBD）进展为乳腺癌相关，以及所选多态性是否改变了BBD女性体重与乳腺癌之间的关联。
在一项正在进行的队列研究的参与者中，994名绝经后白人女性因BBD接受了乳腺活检。其中，61名女性随后患了乳腺癌。1989年在基线时进行了简短问卷调查。使用从1989年采集的血液中提取的DNA确定基因型。
在该队列中，体重指数（BMI）与患乳腺癌的风险呈正相关。相比之下，PON1（Gln192Arg）和LEPR（IVS2 + 6920）的多态性与浸润性乳腺癌的发病风险降低相关。未观察到PPARG、PON2、LPL或TNF的多态性与乳腺癌风险之间或多态性与BMI和乳腺癌风险之间的相互作用有统计学意义的关联。
研究结果表明，PON1和LEPR基因的特定多态性可能在绝经后白人女性BBD进展为乳腺癌中起作用。
