The incidence of colorectal cancer is rising among younger adults, and diet and lifestyle may be the prime suspects.
NEWS.HARVARD.EDU
Harvard doctor explores role of diet in colon cancer risk
Kimmie Ng, a Dana-Farber physician-researcher, answers questions on possible factors driving an increase in colon cancer among young adults.
尋找年輕人中結直腸癌上升的罪魁禍首
隨著美國癌症協會降低其首次結腸癌篩查的推薦年齡，Dana Farber的Kimmie Ng討論了飲食和生活方式在50歲以下患者中疾病發病率的作用。
Jon Chase /哈佛職員攝影師
醫師研究員歡迎篩查指南的轉變，並指出最近關於飲食和疾病復發的研究結果
隨著年輕人中結直腸癌的發病率上升，美國癌症協會已將其首次篩查的推薦年齡從50歲降至45歲。
哈佛大學附屬Dana-Farber癌症研究所的Kimmie Ng博士是最近一項研究的高級作者，該研究將低胰島素負荷飲食 - 水果，蔬菜，全穀物和健康蛋白質和脂肪 - 與結直腸癌復發率顯著下降聯繫起來。 。 Ng在一次採訪中說，飲食和生活方式是50歲以下成年人發病率上升的主要嫌疑人。她還討論了新的美國癌症協會指南以及她自己的工作如何闡明結直腸癌的危險因素。
Q＆A
Kimmie Ng
GAZETTE：美國癌症協會的決定是好的嗎？
NG：我認為這是一個好主意，特別是考慮到年輕患者中結直腸癌發病率的增加。我們還沒有直接的臨床證據證明這樣做具有成本效益，但我們肯定會看到更多50歲以下的患者被診斷患有結腸直腸癌。通常它在診斷時已經轉移。
通過將篩查開始的年齡降低到45歲，我認為我們將能夠捕獲並預防更多這些癌症。
GAZETTE：建議進行更多篩查，在許多人看來，這意味著結腸鏡檢查。但它不一定是那個程序 - 對嗎？
NG：美國癌症協會的主要信息是，任何篩查都比沒有篩查好，所以他們一直非常小心，不優先推荐一種篩選方法。他們建議，只要您通過其指南中的一種方法進行篩選，就會有一個好處。
“越來越多的文獻認為腸道內的細菌正在影響從癌症發展到癌症轉移的各種疾病，以及你對不同治療方法的反應。”
GAZETTE：你對可能導致年輕人增加的原因有什麼看法嗎？
NG：這是一個百萬美元的問題。大多數50歲以下被診斷患有結腸直腸癌的人沒有家族史或遺傳傾向。
我們確實認為有出生隊列效應。隨著歲月的流逝，[結直腸癌]似乎在連續的出生隊列中有所增加。因此，我們認為可能是行為或環境發生了一些變化。我們的主要假設是，與早年成長的人相比，年輕人的久坐行為越來越多，加工食品的增加 - 以及其他飲食變化 - 以及更高的肥胖率，所有這些都與結直腸癌。
有趣的是 - 我們現在正在積極研究這一點 - 這些行為變化是如何與微生物組相關的，以及微生物組如何與癌症和癌症的發展和進展相關聯。越來越多的文獻認為，腸道內的細菌正在影響從癌症發展到癌症轉移的各種疾病，以及您對不同治療方法的反應，即使您是否有治療副作用。
特別是對於結直腸癌，已經有一些不同的細菌種類，如核梭桿菌（Fusobacterium nucleatum），它們與更糟糕的結果有關。由於微生物組受到飲食和生活方式因素的影響，我想知道飲食和年輕人中發病率上升之間的某些聯繫是否可能通過微生物組的變化來調節。
那些每週吃不到一次堅果的人的死亡率降低了7％;每週一次，減少11％;每週兩到四次，減少13％;每週五到六次，減少15％;根據該研究，每週七次或更多次，死亡率降低20％。
堅果消費可降低死亡風險
研究還表明，吃堅果的人體重較輕
研究人員發現，結直腸癌倖存者的飲食和活動模式導致血液中過量的胰島素，癌症復發和死亡的風險更高。吃太多含澱粉和含糖的食物可以產生高胰島素水平。
胰島素與結腸癌有關
仔細看看高碳水化合物飲食和結腸癌的複發
GAZETTE：這引導我們完成您最近的工作。告訴我們這項研究中最重要的發現。
NG：我們研究了由國家癌症研究所管理的1,023名III期結腸癌患者完成的III期臨床試驗，這些患者在手術中完全切除了腫瘤並參加了該試驗，以測試兩種不同的化療方案。
結果是這些方案同樣有效，因此我們能夠匯集所有這些患者，並查看他們自我報告的飲食數據，這些數據是在兩個不同的時間點收集的：開始化療後不久，然後在康復後大約六個月
Seeking a culprit behind rise in colorectal cancer among younger adults
As the American Cancer Society lowers its recommended age for first colon cancer screening, Dana Farber's Kimmie Ng discusses the role of diet and lifestyle in the disease's rise among patients under 50.
As the American Cancer Society lowers its recommended age for first colon cancer screening, Dana Farber's Kimmie Ng discusses the role of diet and lifestyle in the disease's rise among patients under 50.
Jon Chase/Harvard Staff Photographer
Physician-researcher welcomes shift in screening guidelines, notes recent findings on diet and disease recurrence
With the incidence of colorectal cancer rising among younger adults, the American Cancer Society has lowered its recommended age for first screening from 50 to 45.
Dr. Kimmie Ng of Harvard-affiliated Dana-Farber Cancer Institute was senior author of a recent study linking a low-insulin-load diet — fruits, vegetables, whole grains, and healthy protein and fats — to a dramatic drop in colorectal cancer recurrence. Diet and lifestyle are prime suspects in the rising incidence among under-50 adults, Ng said in an interview. She also discussed the new American Cancer Society guidelines and how her own work seeks to illuminate risk factors in colorectal cancer.
Q&A
Kimmie Ng
GAZETTE: Is the American Cancer Society’s decision a good one?
NG: I do think it is a good idea, especially in light of the documented rise in incidence of colorectal cancer in young patients. We don’t have direct clinical evidence yet that this is going to be cost-effective, but we are definitely seeing many more patients under the age of 50 who are getting diagnosed with colorectal cancer. Often it is already metastatic at the time of diagnosis.
By lowering the age at which screening starts to 45, I think that we will be able to catch and prevent more of these cancers.
GAZETTE: The recommendation is for more screening, which in many people’s minds means colonoscopy. But it doesn’t necessarily have to be that procedure — correct?
NG: The American Cancer Society’s main message is that any screening is better than no screening, so they have been very careful in not preferentially recommending one screening method over another. They suggest that as long as you get screened by one of the methods in their guidelines, there could be a benefit.
GAZETTE: Do you have any sense of what might be causing the increase in younger adults?
NG: That is the million-dollar question. Most of those under age 50 being diagnosed with colorectal cancer do not have a family history or genetic predisposition.
We do think there is a birth cohort effect. [Colorectal cancer] seems to have increased in successive birth cohorts as we go through the years. So we think it is probably some change in behavior or the environment that’s causing this. Our leading hypotheses are the increasing amount of sedentary behavior in younger folks compared with people who grew up in earlier times, the increase in processed foods — and other dietary changes as well — and higher rates of obesity, all of which are linked to development of colorectal cancer.
What’s also interesting — and we’re now actively studying this — is how these behavioral changes relate to the microbiome and how the microbiome relates to the development of cancer and cancer growth and progression. There is a growing body of literature that the bacteria in the gut are influencing everything from development of cancer to cancer metastasis to how you respond to different treatments, even whether or not you have side effects from treatment.
And for colorectal cancer specifically, there have been a couple of different bacterial species, such as Fusobacterium nucleatum, that have been linked to a worse outcome. Because the microbiome is so affected by diet and lifestyle factors, I wonder if some of the link between diet and the rising incidence in young folks may be mediated through changes in the microbiome.
GAZETTE: Which leads us to your most recent work. Tell us about the most important findings in this research.
NG: We looked at a completed Phase III clinical trial that was run by the National Cancer Institute of 1,023 Stage III colon cancer patients who had their tumors completely resected at surgery and enrolled in this trial to test two different chemotherapy regimens.
It ended up that those regimens were equally effective, so we were able to pool all those patients and look at their self-reported dietary data, which was collected at two different time points: shortly after starting chemotherapy and then approximately six months after completing chemotherapy.
We averaged the reported dietary intakes from both of those questionnaires for each patient and we calculated an insulin score — both an insulin load, which takes into account how much of each food you’re ingesting, as well as an insulin index, which is the amount of insulin response per kilocalorie. We calculated those scores for each patient.
What we found was that individuals consuming a diet that induced a greater insulin response had a significantly higher risk of their cancer recurring or of dying.
GAZETTE: Can you quantify that a little more?
NG: It was a little more than double the rate of cancer recurrence or death compared to individuals consuming a diet that didn’t induce as much of an insulin response.
GAZETTE: Why did you zero in on insulin specifically?
NG: We have a lot of laboratory evidence that the insulin signaling pathway has tumor growth-promoting properties. It can accelerate cell proliferation. It can prevent apoptosis, which is programmed cell death. These effects can lead to cancer progression and growth.
A lot of dietary factors have been associated with an increased risk of colorectal cancer. We believe the underlying mechanism may be tied to the insulin signaling pathway or energy balance.
This is true for the dietary patterns that we studied. It’s true for obesity. It’s also true for exercise. All of these are related to energy balance and metabolism. So we really wanted to focus on the insulin response to food, rather than just the glucose response to food, which is what the glycemic index measures. We wanted to get right at our central mechanistic hypothesis.
The other reason is that the glycemic index really only deals with the impact of carbohydrates, whereas we know that other types of foods, like proteins and fats, also elicit an insulin response. We wanted to be a little bit more comprehensive.
GAZETTE: What is the take-home message from your work?
NG: This is another addition to the literature that modifiable diet and lifestyle factors actually may be playing an important role in the risk of cancer recurrence and may have a true place in terms of secondary prevention, which is prevention of recurrence in cancer patients.
This is also empowering for patients. I think a lot of times when patients get diagnosed with cancer, the sense of discomfort, unease, and anxiety is related to the loss of control. This is something that patients can take upon themselves to modify, in terms of their diet and physical activity, that may improve their chance of survival.
GAZETTE: How strong generally are the links among cancer, diet, and physical activity?
NG: I recently did a PubMed search on diet and cancer in preparation for a talk, and there were over 44,000 citations. It’s been a topic of interest for well over a century.
The link is stronger for certain types of cancer. Certainly it makes sense for colorectal cancer, where what you’re ingesting comes in direct contact with the area where the tumor is starting. But it also seems to have a very important role in breast cancer. So there are certain cancers where diet and lifestyle seem to be a bit more important.
GAZETTE: What kinds of foods are we talking about in your study?
NG: We have to be a little bit cautious in attributing these high insulin scores to any one particular food, but a lot of them are what you’d expect — a lot of them are carbohydrates. The top food sources for high dietary insulin load are things like potatoes, red meat, milk, breakfast cereals, bread. Yogurt is also high up there.
GAZETTE: And low dietary insulin load? Are we talking about the usual suspects: leafy greens, fruits, vegetables, nuts?
NG: Exactly. Dietary insulin load actually tracks pretty well with the dietary patterns that we’ve studied and published on in the past. A Western dietary pattern is characterized by foods high in processed sugars, high-fat foods, and red meat, which tend to elicit high insulin responses and have been associated with worse outcomes from colorectal cancer. A more Mediterranean or “prudent pattern” diet typically includes foods that are associated with a low insulinogenic potential.
Interview was edited for clarity and length.
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