2012年8月11日 訊 /生物谷BIOON/ --美國加州的馬林縣（Marin County）是世界上乳腺癌患病風險最高的一個縣城,，為何其乳腺癌患病風險如此之高,，科學家們并不清楚,。近日，刊登在國際雜志Journal of the American College of Surgeons上的一篇研究報告中,，來自加利福尼亞大學的研究者揭示了乳腺癌風險相關的影響因子，或許是縣城中的大部分白人婦女的遺傳性狀所引發(fā)的,。研究者從婦女中采集了338份口腔細胞,，研究發(fā)現人們維生素D受體基因的DNA輕微突變和乳腺癌風險直接相關。
研究者發(fā)現高乳腺癌患病風險的女性,，其特殊的維生素D受體突變率是對照組的1.9倍,。Dalessandri博士表示，如今在乳腺癌預防上關于維生素D需要的水平上并沒有給予人們合理的建議,，但是其受體的突變往往是一個重要的風險調節(jié)因子,。當然了這項研究并沒有完全排除別的因素引發(fā)乳腺癌的可能性，但是研究者的發(fā)現也給予了一種合理的解釋,。
十年之后,，揭露新的DNA秘密
以前的研究結果中，研究者對比了馬林縣285個患乳腺癌和286個不患病的婦女,，檢測了其傳統(tǒng)的風險因子,，比如基于年齡限制的風險因子、月經開始的年齡以及首次生育的年齡等,。研究發(fā)現,，患乳腺癌的風險并不因在該地區(qū)所呆的時間而增加,，另外患病婦女相比正常女性每天更易飲酒。
研究者于2003年采集了患者的細胞樣品,，以期望在未來進行研究,，研究者使用了一種名為OncoVue的算法來對基于維生素D受體突變所引發(fā)的乳腺癌風險進行評分，研究中包含有164個患病婦女和174個不患病的婦女,，結果顯示了該軟件在預測乳腺癌風險上具有高的準確性,。研究者發(fā)現遺傳變異-維生素D受體Apa1 A2/A2純合子的多態(tài)性和乳腺癌風險增加直接相關。64%的乳腺癌患者均有這樣的遺傳特點,。
如果維生素D受體的遺傳變異可以證明和乳腺癌有關,，那么或許為乳腺癌的治療或者預防提供一定的思路，后期研究者將深入研究其在臨床上的可用性和其給臨床上所帶來的幫助,。相關研究由加州乳腺癌癌癥中心提供支持,。（生物谷Bioon.com）
編譯自：Marin County, California's High Breast Cancer Rate May Be Tied to Genetics
doi:10.1016/j.jamcollsurg.2012.06.413
PMC:
PMID:
Vitamin D Receptor Polymorphisms and Breast Cancer Risk in a High-Incidence Population: A Pilot Study
Kathie M. Dalessandri, MD, MS, FACS Affiliations Surgeon Scientist, Point Reyes Station, CA Correspondence address: Kathie M Dalessandri, MD, MS, FACS, Surgeon Scientist, PO Box 1173, Point Reyes Station, CA 94956 , Rei Miike, MPH Affiliations Department of Neurological Surgery, Molecular Epidemiology Laboratory, University of California San Francisco, San Francisco, CA , John K. Wiencke, PhD Affiliations Department of Neurological Surgery, Molecular Epidemiology Laboratory, University of California San Francisco, San Francisco, CA , Georgianna Farren, MD Affiliations Marin Community Clinic, San Rafael, CA , Thomas W. Pugh, MS Affiliations InterGenetics Incorporated, Oklahoma City, OK , Sharmila Manjeshwar, PhD Affiliations InterGenetics Incorporated, Oklahoma City, OK , Daniele C. DeFreese, MS Affiliations InterGenetics Incorporated, Oklahoma City, OK , Eldon R. Jupe, PhD, HCLD/CC(ABB)
Background Marin County, California has very high incidence of breast cancer. Traditional risk factors, such as those included in the Gail model, do not effectively stratify breast cancer in this population. This retrospective case-control pilot study evaluates DNA from volunteers from a previous
Marin County breast cancer epidemiology study. A polyfactorial risk model (OncoVue; InterGenetics Incorporated) that incorporates 22 polymorphisms in 19 genes and 5 clinical risk factors was used to stratify risk in Marin County women.
Study Design DNA genotyping was performed on 164 Caucasian women diagnosed with primary breast cancer in Marin County from 1997 to 1999 and 174 age- and ethnicity-matched control subjects. Individual lifetime risks were determined using the polyfactorial risk model and genotype frequencies in women at elevated risk were compared with the overall genotypes. Results The vitamin D receptor VDR ApaI A2/A2 (rs7975232) homozygous polymorphism was present in high frequency in elevated-risk women. Sixty-four percent of elevated-risk women had the VDR Apa1 A2/A2 genotype compared with only 34% in the overall study, a statistically significant 1.9-fold difference (p = 0.0003). VDR Apa1 A2/a1 and a1/a1 genotypes were also present, but in lower frequencies.
Conclusions The high frequency of the VDR Apa1 A2/A2 homozygous polymorphism in women designated as elevated risk for breast cancer by the polyfactorial risk model might be related to the high incidence rates of breast cancer in Marin County, California. Vitamin D supplementation could modify risk of breast cancer in this population.
