J Am Coll Surg：维生素D受体基因突变或与乳腺癌高风险相关

美国加州的马林县（Marin County）是世界上乳腺癌患病风险最高的一个县城，为何其乳腺癌患病风险如此之高，科学家们并不清楚。近日，刊登在国际杂志Journal of the American College of Surgeons上的一篇研究报告中，来自加利福尼亚大学的研究者揭示了乳腺癌风险相关的影响因子，或许是县城中的大部分白人妇女的遗传性状所引发的。研究者从妇女中采集了338份口腔细胞，研究发现人们维生素D受体基因的DNA轻微突变和乳腺癌风险直接相关。

研究者发现高乳腺癌患病风险的女性，其特殊的维生素D受体突变率是对照组的1.9倍。Dalessandri博士表示，如今在乳腺癌预防上关于维生素D需要的水平上并没有给予人们合理的建议，但是其受体的突变往往是一个重要的风险调节因子。当然了这项研究并没有完全排除别的因素引发乳腺癌的可能性，但是研究者的发现也给予了一种合理的解释。

十年之后，揭露新的DNA秘密

以前的研究结果中，研究者对比了马林县285个患乳腺癌和286个不患病的妇女，检测了其传统的风险因子，比如基于年龄限制的风险因子、月经开始的年龄以及首次生育的年龄等。研究发现，患乳腺癌的风险并不因在该地区所呆的时间而增加，另外患病妇女相比正常女性每天更易饮酒。

研究者于2003年采集了患者的细胞样品，以期望在未来进行研究，研究者使用了一种名为OncoVue的算法来对基于维生素D受体突变所引发的乳腺癌风险进行评分，研究中包含有164个患病妇女和174个不患病的妇女，结果显示了该软件在预测乳腺癌风险上具有高的准确性。研究者发现遗传变异-维生素D受体Apa1 A2/A2纯合子的多态性和乳腺癌风险增加直接相关。64%的乳腺癌患者均有这样的遗传特点。

如果维生素D受体的遗传变异可以证明和乳腺癌有关，那么或许为乳腺癌的治疗或者预防提供一定的思路，后期研究者将深入研究其在临床上的可用性和其给临床上所带来的帮助。相关研究由加州乳腺癌癌症中心提供支持。

编译自：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.