最新醫學研究嘗試阻斷癌症基因的遺傳

To shield any future children from the fear she harbors of getting breast cancer, Katie Dowdy underwent a controversial procedure to select embryos of hers that were free of a genetic mutation linked to the disease.

爲了不讓孩子將來像自己一樣害怕患上乳腺癌，凱蒂·道迪(Katie Dowdy)做了一項充滿爭議的檢查，以挑選出不攜帶一種被認爲與乳腺癌相關的基因突變的胚胎。

Deciding to have the procedure, called preimplantation genetic diagnosis, or PGD, wasn't easy, says Ms. Dowdy. Her husband initially 'worried about playing God,' she says. 'I thought, if I could have a healthy baby who doesn't have to worry about the same thing I did, why wouldn't I?' says the 34-year-old, who hasn't had cancer. The couple, who live in Castle Pines, Colo., now have two young girls, both born using PGD.

道迪說，決定做這項名叫“着牀前遺傳學診斷”（簡稱PGD）的檢查並不是一個容易的過程。她說，起初丈夫“擔心自己是在扮演上帝的角色”。現年34歲、沒有得過癌症的她說：“我想，如果我能有一個健康的孩子，不需要擔心我所擔心的事情，那我爲什麼不做呢？”夫婦倆家住科羅拉多州派恩堡，現有兩個年幼的女兒，都是在做了PGD之後出生的。

Preimplantation genetic diagnosis has long been available during IVF, or in vitro fertilization, to eliminate the risk of passing on severe disorders such as spinal muscular atrophy and cystic fibrosis. Now, fertility clinics say they are seeing a small but increasing number of women choosing PGD to avoid giving birth to children who carry mutations in the BRCA genes, which increase the risk for breast and other cancers.

防範於未然着牀前遺傳學診斷(PGD)檢查胚胎有沒有某種可能會從父母身上遺傳而來的遺傳缺陷。以下是PGD檢查的一些疾病：

'It's on the rise because more people are becoming aware that there's a genetic component to breast cancer,' says Mark Hughes, founder of Genesis Genetics, in Plymouth, Mich., which offers reproductive-genetics-diagnosis services to fertility clinics nationwide.

囊性纖維化

Critics fear genetically vetting embryos can be used to create so-called designer babies. Embryos with the gene mutation may be discarded, which some critics also oppose. Gender selection is one form of embryo-testing that stirs ethical questions. Some clinics will agree to select for a specific sex only for health reasons -- to avoid a disease such as hemophilia, for example, which typically is passed only to boys. Opponents of PGD for breast cancer also say that having a BRCA-gene mutation doesn't mean a person will necessarily get the disease and that there are options for detecting and treating the cancer.

血友病

A parent with a mutation on the BRCA1 or BRCA2 genes has a 50-50 chance of transmitting it to the next generation. Between 45% and 65% of women with the mutations are expected to be diagnosed with breast cancer by age 70, according to the National Cancer Institute. That compares with about 12% of women in the general population.

亨廷頓氏舞蹈症

BRCA mutations, which also increase the risk for ovarian, prostate and other cancers in men and women, are relatively rare, accounting for 5% to 10% of all breast cancers. Some women undergo prophylactic mastectomy to reduce their chances of getting the disease.

馬方氏綜合徵

In Ms. Dowdy's family, the specter of breast cancer hovers. Her paternal grandmother died in 1979, five months before Ms. Dowdy was born. Several of her grandmother's sisters also got breast cancer. Ms. Dowdy's father had a genetic test and found he had inherited the BRCA1 mutation. When she was 27, a test showed Ms. Dowdy also had the mutation.

肌肉萎縮

After her aunt, who shares the same mutation, had a prophylactic mastectomy, Ms. Dowdy researched her options and learned about PGD. Ms. Dowdy says she and her husband had struggled to conceive. Figuring they would need fertility assistance, also doing PGD to avoid passing on the BRCA mutation seemed like an obvious precaution.

地中海貧血

The PGD process begins with standard IVF. After two weeks of hormonal stimulation, eggs are retrieved, fertilized and left to multiply for five days. Then a laboratory scrutinizes several cells, looking for gene mutations. The analysis isn't believed to harm the embryo. Embryos without BRCA mutations are earmarked for transfer into a woman's uterus.

黑蒙性白癡

Two of Ms. Dowdy's seven embryos were BRCA-mutation free. Both were transferred to her uterus. One implanted and grew to become a daughter, Reagan, born in 2010. Ms. Dowdy and her husband opted for PGD again to conceive another child, Mackenzie, born in March.

脊髓性肌萎縮

Only recently have some doctors started discussing PGD with women who have a breast-cancer mutation. More often, BRCA-positive women learn about the procedure on their own. 'We write about it in our newsletter and we've done webinars on it, but not everyone knows about it,' says Sue Friedman, executive director of Force, a nonprofit patient-support group focused on hereditary breast and ovarian cancers.

鐮狀細胞貧血

For women who have no trouble conceiving, the choice to do PGD involves the added hassle of fertility treatment. PGD can add about $6,000 to the price of IVF, which runs at least $10,000, depending on the clinic, plus thousands of dollars more for medications.

資料來源：紐約大學生殖中心(NYU Fertility Center)很久以來，在試管受精的操作過程中，都可以通過着牀前遺傳學診斷來消除將脊髓性肌萎縮、囊性纖維化等嚴重缺陷遺傳下去的風險。而現在，據生殖醫院說，數量不大但越來越多的女性都在選擇做PGD以避免生下攜帶BRCA基因突變的孩子。BRCA基因突變會增加患乳腺癌和其他癌症的風險。

'It's by no means 100% [of eligible women] who are choosing to do it,' says William Schoolcraft, medical director of the Colorado Center for Reproductive Medicine in Lone Tree, Colo., and Ms. Dowdy's doctor. Dr. Schoolcraft says he has done about 10 PGD procedures to eliminate a BRCA mutation in the past three years. He has heard some patients say ' 'My grandma had it, my aunt had it, my mom had it. I want to stop this train.' Others have the attitude that if my baby turns out like me, so be it.'

密歇根州普利茅斯堡的Genesis Genetics爲全國生殖醫院提供生殖遺傳學診斷服務。創始人馬克·休斯(Mark Hughes)說：“之所以數量在上升，是因爲越來越多的人懂得乳腺癌包含遺傳成分。”

Even after an embryo selected through PGD is successfully implanted, some doctors recommend an amniocentesis or another prenatal test called CVS to make sure there isn't a BRCA-gene mutation.

批評者擔心，經過遺傳學檢查的胚胎有可能被用於製造“定製嬰兒”(designer baby)。含有基因突變的胚胎可能被拋棄，這也是一些批評者所反對的。性別選擇是激起倫理爭議的胚胎檢查形式之一。一些醫院只會同意出於健康原因而選擇某個性別，比如說規避常常只遺傳給男孩的血友病等。乳腺癌PGD反對者還說，攜帶BRCA基因突變並不意味着人一定會得這種病，而且乳腺癌的偵測和治療還有其他方法。

'You have to think of it from the perspective of a woman whose life has been turned upside down by breast cancer and the guilt associated with choosing to have a baby that could have those same problems,' says James Grifo, director of the Division of Reproductive Endocrinology and Infertility at NYU Fertility Center.

攜帶BRCA1或BRCA2基因突變的父母有50%的概率將它遺傳給下一代。根據國家癌症研究所(National Cancer Institute)數據，45%到65%攜帶這些突變的女性預計會在70歲之前被診斷出乳腺癌。相比之下，一般女性的這個概率在12%左右。

Bonnie Rochman

BRCA突變也會增加男性和女性罹患上卵巢癌、前列腺癌等癌症的風險。這類突變相對少見，佔所有乳腺癌的5%到10%。有些女性通過做預防性乳房切除術來降低患乳腺癌的風險。