乳腺癌是女性的头号杀手，估计全球每8名女性中就有1人患有乳癌。近日，丹麦的研究人员报道说，他们已经分离出一个与乳腺癌发生有关的新基因。这个叫做CHEK2的基因是到目前为止发现的第三个乳腺癌基因。
通过对根本哈根的9000名丹麦人的调查研究发现，这种新发现的CHEK2基因的一种突变能使乳腺癌发生的风险增加三倍。这项研究的结果将公布在即将刊出的Journal of Clinical Oncology杂志上。
另外两个乳腺癌基因是BRCA1和BRCA2。这项研究是对具有乳腺癌家族史的女性和已经患乳腺癌的男性进行检测，看他们是否发生了CHEK2基因的突变。这项研究的结果增加了人们对乳腺癌遗传影响因子的了解。
乳腺癌是乳腺导管上皮细胞在各种内外致癌因素的作用下，细胞失去正常特性而异常增生，以致超过自我修复的限度而发生癌变的疾病。临床以乳腺肿块为主要表现。乳腺癌是最常见和最重要的乳房疾病，其发病率为23／10万。临床主要表现是乳块。
本病大多数发生在40 -60岁，亦即更年期前后的妇女。全世界乳腺癌发生率正以每年0.2％-3％的幅度上升，在欧美等西方发达国家，乳腺癌已成为妇女的主要死因之一，每8-10名妇女中，就有1人在其一生中将患乳腺癌。我国发病率也呈上升趋势，在北京、上海、天津等大城市，乳腺癌已占妇女恶性肿瘤发病的首位。
英文原文：
Variation in CHEK2 gene may triple breast cancer risk
Alexandria, VA -- A study of more than 9,000 Danish residents shows that a specific variation in the CHEK2 gene may triple a woman's risk of developing breast cancer in her lifetime. The study--the first to examine the prevalence of the CHEK2 mutation in the general population and the associated cancer risk--will be published online July 31 in the Journal of Clinical Oncology.
"Our study shows that women in the general population who carry a specific CHEK2 mutation are three times as likely as women without the mutation to develop breast cancer," said Borge G. Nordestgaard, MD, Professor and Chief Physician, Department of Clinical Biochemistry, Herlev University Hospital, Denmark, and lead author of the study. "The findings suggest that CHEK2 could serve as a useful biomarker for identifying women who would benefit from heightened, regular screening for breast cancer."
CHEK2, which belongs to a class of genes known as "tumor suppressors," is responsible for repairing DNA damage and preventing the uncontrolled division of cells, which can lead to cancer. In this study, researchers looked for a specific mutation, known as CHEK2*1100delC, which impairs the gene's ability to fix damage to DNA.
Previous case-control studies have shown an association between this specific CHEK2 mutation and breast, prostate, and colorectal cancer. Researchers designed this study to assess the prevalence of the mutation in the population at large and to examine its impact on cancer risk.
Dr. Nordestgaard and his colleagues randomly selected 9,231 Danes who had participated in the Copenhagen City Heart Study--a cohort of more than 20,000 Danish men and women that followed participants for an average of 34 years for cancer development.
The researchers found that 0.5% of all participants carried the CHEK2 mutation. Among women who carried the CHEK2 mutation, 12% developed breast cancer, compared to 5% of non-carriers. Adjusting for other factors, such as age, body mass index, and use of hormone replacement therapy, researchers found that women who carried the mutation were 3.2 times as likely as women who had normal CHEK2 genes to develop breast cancer. Those most at risk were mutation carriers on hormone replacement therapy who were more than 60 years old and overweight--who had a 24% chance of developing the disease within 10 years. The researchers found no statistically significant association between the CHEK2 mutation and prostate, colorectal, or general cancer risk.
By way of comparison, other studies have shown that BRCA 1/2 mutations occur in roughly 1% of the general U.S. population. Women with a BRCA1 or BRCA2 mutation have a dramatically heightened risk of developing breast cancer--up to an 80% chance of developing the disease during their lifetime and at a much younger age than women who do not have one of these two mutations. Life-time risk of breast cancer among women in the general population is approximately 13%.
"There are clearly a number of genetic and environmental factors in play when it comes to the development of breast cancer," said Dr. Nordestgaard. "The identification of CHEK2 as a biomarker gives us a better picture of the genetic risk factors, and may help to identify a significant subset of women who would benefit from more vigilant screening for the disease."
According to the study's authors, a key limitation of the research was that it included only white Danish women; it is not known to what extent CHEK2 mutations are found among black, Hispanic or other women, or whether the breast cancer risk associated with CHEK2 mutations among these women is of a similar magnitude to those involved in this study.
