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作者：Zosia Chustecka  
出處：WebMD醫學新聞

　　June 2, 2010 — 對「British Million Women Study」這項研究資料進行的一個大型分析發現，乳癌環境風險因素、與乳癌風險有關的低外顯率易感型單一核苷酸多型性(SNPs)之間沒有交互作用，這篇新研究線上發表於6月2日的The Lancet期刊。
　　
　　這篇研究探討已發表於基因組關聯研究的12種與乳癌有關的SNP，報告指出乳癌風險略為增加(每種對偶基因的相對風險約為1.2)，該研究並未探討BRCA1和BRCA2基因，這兩者有較高的乳癌風險，但是只有相對少數婦女有。
　　
　　第一作者、英國牛津大學癌症流行病學小組的Ruth Travis博士在聲明中表示，我們探討乳癌的生活型態因素，如荷爾蒙替代治療(HRT)、飲酒與生育史是否會影響基因風險，答案是不會。
　　
　　來自同單位的共同作者Jane Green醫師表示，本研究為此問題增加了一項證據，幫助我們瞭解基因和生活型態如何影響乳癌風險，基因只影響少部分乳癌，對於多數婦女，主要的風險依舊是生活型態因素，例如生育、使用HRT、肥胖與飲酒。好消息是，這些因素有些是可以調整的，所以，藉由改變這些行為，婦女可以改變她們的乳癌風險。
　　
　　【檢測基因–環境交互作用】
　　研究者使用「Million Women Study」這項研究的資料，包括了130萬名中年婦女(平均年紀56歲)，於1996至2001年間獲邀進行例行性乳房攝影。他們確認了7610名婦女發生乳癌，將她們和沒有該病的10,196名控制組傅女進行比較。
　　
　　該團隊接著檢測已經證實和乳癌有關的12個核苷酸多型性和10個乳癌環境風險因素(初經年紀、生產次數、第一次分娩時年紀、哺母乳、停經狀態、停經時年紀、使用HRT、身體質量指數、身高與飲酒)之間的交互作用。研究者指出，對於「Million Women Study」整個研究世代，這10 個環境因素對乳癌發生率的影響多數已經顯示相當重要。
　　
　　該團隊報告指出，並沒有任何具有說服力的基因-環境交互影響證據。
　　
　　研究者指出，多數環境因素和乳癌風險之間的關聯，比我們研究的基因因素更強烈，目前有使用HRT是這個世代最強的環境風險因素，相對風險比此一研究探討的任一種SNP都要高出許多。
　　
　　他們指出，多數SNP的功能並不清楚，後續研究應證明它們是實際因果變化的唯一標記。
　　
　　作者們指出，因為研究設計，另外5個和乳癌有關的SNP已經被確認，不過乳癌相關相對風險不大。
　　
　　安大略多倫多Women's College Research Institute的Steven Narod醫師在編輯評論中表示，當然，一定會有更多SNP需要研究，但是，迄今，這些對乳癌的影響都不大。
　　
　　他認為，SNP方式可能被「過度促銷」了，其他得出的結論認為，不論是單一SNP或合併，並無助於預測癌症風險。
　　
　　最近，許多專家對那些直接向大眾銷售、SNP為主的基因易感性檢測銷售廣告提出顧慮，如同Medscape Oncology之前的報導。
　　
　　Narod醫師表示，回到預防腫瘤醫學的議題，重點依舊在於，為何25歲時的生育會影響65歲時的乳癌風險。
　　
　　他結論表示，不幸的是，基因研究尚未提供任何新線索。
　　
　　作者們和編輯皆宣告沒有相關財務關係。
　　
　　Lancet. 線上發表於2010年6月2日。


Lifestyle Factors Do Not Influence Genetic Risk for Breast Cancer

By Zosia Chustecka
Medscape Medical News

June 2, 2010 — A large analysis of data from the British Million Women Study has found no interaction between environmental risk factors for breast cancer and common low-penetrance susceptibility single-nucleotide polymorphisms (SNPs) that have been associated with breast cancer risk. The new study is published online June?2 in The Lancet.

This study looked at 12 SNPs that have been associated with breast cancer in published genome-wide association studies that have reported a small increase in the risk for breast cancer (relative risk of around 1.2 per allele). The study did not did not investigate BRCA1 and BRCA2 genes, which confer a much higher risk for breast cancer but are found in a relatively smaller number of women.

"We looked at whether lifestyle factors for breast cancer, such as hormone-replacement therapy (HRT), alcohol consumption, and reproductive history, influence the genetic risk. The answer is, they do not," said lead author Ruth Travis, DPhil, from the Cancer Epidemiology Unit at Oxford University, United Kingdom, in a statement.

"This study provides another piece in the jigsaw, helping us to understand how genes and lifestyle affect breast cancer risk," added coauthor Jane Green, MD, from the same unit. "Genes account for only a small proportion of breast cancers and, for most women, the main risk factors remain the lifestyle factors, such as childbearing, use of HRT, obesity, and alcohol consumption. The good news is that some of these are modifiable, so by changing their behavior women can alter their risk of breast cancer."

Testing Gene–Environment Interactions

The researchers used data collected in the Million Women Study, which involved 1.3?million middle-aged women (mean age, 56 years) who had been invited for a routine mammogram from 1996 to 2001. They identified 7610 women who developed breast cancer, and compared them with 10,196 control subjects without the disease.

The team then tested for interactions between 12 polymorphisms that had previously been associated with breast cancer and 10 environmental risk factors for breast cancer (age at menarche, parity, age at first delivery, breast-feeding, menopausal status, age at menopause, use of HRT, body mass index, height, and alcohol consumption). The researchers note that the effects of most of these 10 environmental factors on breast cancer incidence have already been shown to be highly significant for the entire Million Women Study cohort.

There was no convincing evidence for any gene–environment interactions, the team reports.

"Most of the environmental factors are more strongly associated with breast cancer risk than are the genotypic factors we studied" note the researchers. "Current use of HRT is the strongest environmental risk factor in this cohort?.?.?.? and the associated relative risks are much greater than for any of the SNPs studied here," they add.

"The function of most of the SNPs is unclear, and future investigations might show them to be only markers of true causal variants," they add.

The authors note that, since they designed their study, another 5 SNPs associated with breast cancer have been identified, although the associated relative risk for breast cancer is not large.

"Of course, there are always more SNPs to study, but to date, none of these seem to contribute to breast cancer in a big way," says Steven Narod, MD, from the Women's College Research Institute in Toronto, Ontario, in an accompanying editorial.

The SNP approach might have been "oversold," he suggests. "Others have come to the conclusion that SNPs, alone or in combination, are not that helpful in predicting cancer risk."

Recently, several experts have expressed concern over the advertising of genetic-susceptibility tests based on SNPs that are sold directly to the general public, as previously reported by Medscape Oncology.

Coming back to the issue of preventive oncology, Dr. Narod says that the crucial question that remains is why having a baby at age 25 should influence the risk for breast cancer at age 65.

"Unfortunately the genes studied here do not provide any new clues," he concludes.

The authors and editorialist have disclosed no relevant financial relationships.

Lancet. Published online June?2, 2010.