僅半數大腸直腸癌與肥胖及少動有關


  【24drs.com】越來越多人認為肥胖和少運動與大腸直腸癌有關,但是一篇新研究認為僅半數案例和這些因素有關。
  
  這篇線上發表於2月26日癌症研究期刊的研究發現,體重增加和運動量少這兩個因素,只和生物標記CTNNB1陰性者的大腸直腸癌風險增加有關,而這類型患者之比率為檢測案例的54%。
  
  至於CTNNB1陽性的大腸直腸癌、其餘的46%檢測案例,則未有前述關聯。哈佛公衛學院流行病學副教授、達那-法伯癌症研究中心病理科副教授、該研究的資深作者Shuji Ogino博士表示,看來這些癌症和這些生活型態因素無關。
  
  研究者報告指出,這項結果強調了腫瘤異質性的重要性,一般將大腸直腸癌視為單一疾病治療,但這篇研究顯示出兩種相當不同的亞型。
  
  Ogino博士指出,如果醫師們可以確認哪些患者會發生CTNNB1陰性癌症,那麼就可以更強力建議運動。
  
  Ogino博士解釋,或許也可以為這兩種亞型發展出不同的治療方式。研究者推測,這兩種亞型對於能量平衡的反應方式有所不同,認為是過度的能量平衡促使CTNNB1陰性細胞發生。
  
  接下來,我們應發展CTNNB1與相關分子的標靶化療預防和治療,可藉以降低癌症風險和促進健康,特別是肥胖者。
  
  研究者分析了2篇大型的全國性前瞻研究;分別是「護士健康研究」109,046名婦女和「醫療專業人員研究」47,684名男性的資料;診斷有大腸直腸癌的2,263個案例中,發現861例有CTNNB1組織表現,這些腫瘤中,有54%是CTNNB1陰性。
  
  研究者強調,對於這個亞型,體重增加和運動程度降低者的關聯達統計上的顯著意義。
  
  較高的身體質量指數(BMI)和CTNNB1陰性大腸直腸癌風險顯著較高有關(每增加5 kg/m2之多變項風險比(HR)為1.34;P trend< .0001)。運動量和 CTNNB1陰性大腸直腸癌風險顯著降低有關(每週每小時代謝當量每增加10之HR為0.93;P trend= .044)。
  
  Ogino博士等人在之前的研究(JAMA. 2011;305:1685-1694)中發現,過度的能量平衡對於發生CTNNB1陰性大腸直腸癌有所影響,但是對CTNNB1陽性癌症則無影響。
  
  他們寫道,與以前的資料統整後,這次的研究結果認為,腫瘤的CTNNB1狀態可能會影響細胞對肥胖和運動之敏感性,且不只已存在的腫瘤惡化,也包括還未被臨床偵測的初期腫瘤。
  
  研究者指出,機轉可能包括胰島素和類胰島素生長因子(IGF),這些被公認是研究肥胖和大腸直腸癌之間因果關聯的主要因素,在一些細胞中,胰島素和IGF促進細胞存活和增生,至少有一部分是透過CTNNB1訊息路徑的暫時活化。
  
  Ogino博士表示,這是首度如此詳盡地報告,以前的研究顯示BMI增加和微小衛星標記穩定之大腸直腸癌風險增加有關,但那僅僅是概念上的關聯。
  
  資料來源:http://www.24drs.com/professional/list/content.asp?x_idno=6985&x_classno=0&x_chkdelpoint=Y
  

Only Half of Colorectal Cancers Linked to Obesity and Inactivity

By Zosia Chustecka
Medscape Medical News

Obesity and physical inactivity have been increasingly linked to colorectal cancer, but a new study suggests that these risk factors are only important in about half of all cases.

The study, published online February 26 in Cancer Research, found that increased body weight and decreased levels of physical activity are only associated with an increased risk for colorectal cancer that tests negative for the biomarker CTNNB1. This subtype accounted for 54% of the cases tested.

For CTNNB1-positive colorectal cancer, which accounted for the remaining 46% of cases tested, no such association was found. It appears that these cancers are independent of those lifestyle factors, senior author Shuji Ogino, MD, PhD, associate professor of pathology at the Dana-Farber Cancer Institute and associate professor of epidemiology at the Harvard School of Public Health in Boston, Massachusetts, told Medscape Medical News.

This finding highlights the importance of tumor heterogeneity, the researchers report. Typically, colorectal cancer is treated as a single disease, but this study shows 2 quite different subtypes.

"If physicians are able to identify individuals who are prone to develop CTNNB1-negative cancer, then it would be possible to strongly recommend physical activity," Dr. Ogino noted.

It might also be possible to develop different treatments for the 2 subtypes, Dr. Ogino explained. The researchers speculate that there is a difference in the way the 2 subtypes react to energy balance, and suggest that an excess energy balance drives the growth of CTNNB1-negative cells.

"For the next step, we should develop targeted chemoprevention and treatment for CTNNB1 and related molecules, which can lower cancer risk and enhance health status, especially in obese individuals," he said.

Both Associations Significant, But Only for 1 Subtype

The researchers analyzed 2 large nationwide prospective studies; data on 109,046 women came from the Nurses' Health Study and data on 47,684 men came from the Health Professionals Study.

CTNNB1 tissue-expression results were available for 861 of the 2263 diagnosed cases of colorectal cancer. Of these tumors, 54% were CTNNB1-negative.

For this subtype, associations were statistically significant for increased body weight and for decreased levels of physical activity, the researchers emphasize.

Higher body mass index (BMI) was associated with a significantly higher risk for CTNNB1-negative colorectal cancer (multivariate hazard ratio (HR) for increments of 5 kg/m2, 1.34; P trend < .0001). Physical activity was associated with a significantly lower risk for CTNNB1-negative colorectal cancer (multivariate HR for increments of 10 MET-h/week, 0.93; P trend = .044).

Different Reaction to Energy Balance

In a previous study from their laboratory, Dr. Ogino and colleagues found that an excess energy balance had an effect on the progression of CTNNB1-negative colorectal cancer, but not on CTNNB1-positive cancer (JAMA. 2011;305:1685-1694).

"Together with our previous data, our current findings suggest that tumor CTNNB1 status may influence cellular sensitivity to obesity and physical activity not only during progression of an established tumor, but also during earlier steps of tumor development up to clinical detection," they write.

The mechanism may involve insulin and insulin-like growth factors (IGF), which are the main suspects in the search for putative mediators of the causal link between obesity and colorectal cancer. In a number of cell lines, insulin and IGF promote cell survival and proliferation, at least in part through transient activation of the CTNNB1 signaling pathway, the researchers note.

This is the first time that this finding has been reported in such detail, Dr. Ogino told Medscape Medical News. Previous studies have shown an association between increased BMI and an increased risk for microsatellite stable colorectal cancer, but that was just "a conceptual link."

The authors have disclosed no relevant financial relationships.

Cancer Res. Published online February 26, 2013.

    
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