为何1/3的结肠癌风险源于进食红肉?

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Scienceblog

2013.10.24.

 

【编者导读】据美国人类遗传协会2013年年会报道,在一项超过1.8万人的研究中发现:36%的人携带rs4143094基因变异(该基因位于10号染色体),携带该基因变异的人进食红肉及加工肉类后,罹患结肠直肠癌的风险显著增高。研究者同时也强调:“并不是说如果你不携带这个基因变异,你就应该吃所有你想吃的红肉。”研究还发现携带rs1269486基因变异(该基因位于8号染色体)的人,进食蔬菜水果则具有抗癌作用。

 

据国际最大的人类遗传学会议——美国人类遗传协会2013年年会报道,每3个人中就有1人会发生的一种常见基因变异(编注:即基因突变),该基因变异会显著增加由于进食红肉和加工肉类所引发的结肠癌的发病风险。

除了确定由于进食红肉或加工肉类而增加罹患结肠直肠癌风险的基因,研究首先在全基因组水平确定基因与膳食之间的相互影响,另外还显示了另一个特定的基因变异,该基因变异看起来会因是否多吃蔬菜、水果以及高纤维素食品而发生改变,从而降低罹患结肠直肠癌的风险。

本研究的主要作者:美国南加州大学(USC)凯克医学院预防医学助理教授珍妮•菲格雷多(Jane Figueiredo)博士说:“对于结肠直肠癌来说,饮食是一个可变的危险因素。我们的研究首先是在基因组水平探究某些人是否具有较高或较低的发病风险。这些信息有助于我们能更好地理解生物学,而且有可能在未来采取具有针对性的靶向预防措施。“

菲格雷多补充道:“但是我们并不是说如果你不具有这个基因变异,你就应该吃所有你想吃的红肉。具有该基因突变等位基因的人,与肉类相关的基线风险已经非常严重了,但是如果摄入较多的加工肉类的话,会使罹患结肠直肠癌的风险更高。”

文章的第一作者:乌尔丽克•彼得斯(Ulrike Peters)博士,来自西雅图弗莱德•哈钦森癌症研究中心公共健康科学部(Fred Hutchinson Cancer Research Center’s Public Health Sciences Division),彼得斯博士说:我们都听说过某种食物能够降低或增加罹患某种疾病(例如癌症)风险的报道。但是,目前尚未对人类个体的基因变异将如何改变饮食对疾病的作用展开全面探究。

研究人员系统性地搜索了超过270万个基因序列与进食红肉及加工肉类之间的相互影响。该项研究对9,287名结肠直肠癌患者以及作为对照组的9,117名非罹患肿瘤者进行了检测。

研究发现:在进食加工肉类者中,如果携带rs4143094基因变异的个体将明显增高罹患结肠直肠癌的风险。这个基因变异位于10号染色体上包含转录因子GATA3的区带,目前已经发现该转录因子基因与一些肿瘤相关。GATA3基因所编码的转录因子通常在免疫系统中发挥作用,但是人群中约有36%的人携带该基因的变异。

研究者们推测,加工肉类的消化可能会促进能够启动癌症发生发展的免疫应答(immunological response)或炎症应答(inflammatory response)。GATA3转录因子通常可以抑制免疫应答或炎症应答反应。然而,一旦GATA3基因发生变异,就会编码出调节异常的转录因子,从而影响其发挥抑制免疫应答的作用。

但是,另外一些基因变异可能是有利的。在统计学上,饮食与基因相互作用具有显著性意义的另外一个变异是位于8号染色体上的rs1269486。研究表明,当面对结肠直肠癌风险时,如果您属于具有这个基因变异的人群,则吃蔬菜水果可能对您更好(编注:即具有抗癌作用)。

该项研究属于全球多个机构合作的一部分,这些机构是国际NIH(美国国立卫生研究院)资助的结肠直肠癌遗传学与流行病学联盟(the international NIH-funded Genetics and Epidemiology of Colorectal Cancer Consortium,GECCO)。

彼得斯说:“GECCO的目标是继续发现与结肠直肠癌相关的其他基因变异,该目标可以通过探索在环境或者生活方式危险因素作用下基因变异如何发生改变,还包括如何影响患者的治疗反应(patient treatment response)以及生存率(survival)的生物标记物(biomarkers)。”彼得斯强调需要更进一步研究,从而揭示罹患结肠直肠癌风险中基因调节某些食物的摄入量的具体机制。

在绝大部分种族中,结肠直肠癌高居肿瘤死亡率的第三位。结肠直肠癌是一种多因素疾病,与生活方式、环境因素以及基因密切相关。整个基因组中已经找到超过30种的结肠直肠癌易感基因(genetic susceptibility alleles)。其中包括与结肠直肠癌具有强相关性的罕见基因变异,也有低危的常见变异。

菲格雷多说:“结肠直肠癌是一种受膳食类型强烈影响的疾病。我们展示了这些关系的生物学基础,而且揭示了基因变异是否会使某些人对食物中的某种致癌物(carcinogens in food)更易感或更不易感,这可能在未来对预防及人类健康具有重要意义。”

翻译:悠悠步行者

来源:scienceblog

http://scienceblog.com/67430/why-1-in-3-people-risk-colon-cancer-from-eating-red-meat/#yfJpORyA3JwM2G1x.99

 

Why 1 in 3 people risk colon cancer from eating red meat

October 24, 2013

A common genetic variant that affects 1 in 3 people significantly increases the risk of colorectal cancer from the consumption of red meat and processed meat, according to a study presented today at the annual American Society of Human Genetics 2013 meeting, the largest gathering of human geneticists in the world.

In addition to identifying a gene that raise risk for colorectal cancer from eating red ot processed meat, the study — the first to identify the interactions of genes and diet on a genome-wide scale, —also reveals another specific genetic variation that appears to modify whether eating more vegatables, fruits and fiber actually lowers your colorectal cancer risk.

“Diet is a modifiable risk factor for colorectal cancer. Our study is the first to understand whether some individuals are at higher or lower risk based on their genomic profile. This information can help us better understand the biology and maybe in the future lead to targeted prevention stratagies,” said lead author Jane Figueiredo, Ph.D. Assistant Professor of Preventive Medicine at the Keck School of Medicine of USC.

“But we are not saying that if you don’t have the genetic variant that you should eat all the red meat you’d like,”Figueiredo added. “People with the genetic variant allele have an even higher increased risk of colorectal cancer if they consume high levles of processed meat, but the baseline risk associated with meat is already pretty bad.”

We’ve all heared reports about how certain foods may lower or raise the risk for certain disease, such as cancer. But how our personal genetic variations modify the effects of diet on disease has not yet been thoroughly investigated, said senion author Ulrike Peters, Ph.D., M.P.H, of the Fred Hutchinson Cancer Research Center’s Public Health Sciences Division.

The researchers systematically searched the more than 2.7 million genetic sequences for interactions with consumption of red and processed meat. The study looked at 9,287 patients with colorectal cancer and a control group of 9,117 individuals without cancer.

The risk of colorectal cancer associated with processed meat was significantly higher among people with the genetic variant rs4143094, the study shows. This variant is located on the same chromosome 10 region that includes GATA3, a transcription factor gene previously linked to several forms of cancer. The transcription factor encoded by this gene normally plays a role in the immune system, but carries this genetic variant in about 36 percent of the population.

The researchers speculate that the digestion of processed meat may promote an immunological or inflammatory response that may trigger tumor development. The GATA3 transcription factor normally would help suppress the immunological or inflammatory response. However, if the GATA3 gene region contains a genetic variant, it may encode a dysregulated transcription factor that impacts its ability to suppress the response.

But other genetic vatiants may be beneficial: On chromosome 8, another statistically significant diet-gene interaction was found in variant rs1269486. For people with this variant, eating your fruits and veggies may be even better for you when it comes to colorectal cancer risk, the research shows.

The study is part of an ongoing collaboration among multiple institutions worldwide, the international NIH-funded Genetics and Epidemiology of Colorectal Cancer Consortium (GECCO).

“GECCO aims to continue to discover additional colorectal cancer-related variants by investigating how genetic variants are modified by other environmental and lifestyle risk facors, including biomarkers as well as how they influence patient treatment response and survival,”Peters said, emphasizing how much further research is requied to uncover the specific mechanisms by which genes modulate the intake of certain foods on colorectal cancer risk.

Colorectal cancer is a multi-factorial disease attributed to lifestyle, environmental and genetic causes, and the third leading cause of cancer death in both men and women across most racial groups. Over 30 genetic susceptibility alleles for colorectal cancer have been pinpointed throughout the genome. They include rare variants that have a strong impact on risk and common variants that are low risk.

“Colorectal cancer is a disease that is strongly influenced by certain types of diets,” Figueiredo said. “We’re showing the biological underpinnings of these correlations, and understand whether genetic variation may make some people more or less sueceptble to certain carcinogens in food, which may have future important implications for prevention and population health.”