COMMENTARY

Modifiable Risk Factors for Colon Cancer

What Should We Tell Our Patients?

David A. Johnson, MD

Disclosures

May 02, 2018

Hello. I'm Dr David Johnson, professor of medicine and chief of gastroenterology at Eastern Virginia Medical School in Norfolk, Virginia.

Welcome back to another episode of GI Common Concerns.

For today's discussion, I want to focus on primary and secondary prevention of colorectal polyps, neoplastic polyps (both adenomas and serrated lesions), and colon cancer.

Typically, this topic comes up in conversations when patients have been diagnosed with colon cancer or colon polyps, have a family history of colon cancer or colon polyps, or they know someone with colon cancer or colon polyps. They ask, "What can I do to help prevent this?"

Prevention may be on a primary basis or secondary basis. The data on this are not strong, but let's begin where the data are the strongest.

Smoking and Risk for Colon Cancer

Smoking is a strong risk for primary development of colon cancer and advanced neoplasms.[1] The risk for sessile serrated lesions is very strong with cigarette smoking.[2] Smoking is associated with a nearly twofold increase in risk for colon polyps.[3] I tell patients that this is on par with having a first-degree relative with colon cancer. It is incredibly important.

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We know that smoking increases the risk [for colon cancer] at an earlier age, and adenoma detection is higher in patients who are smokers at an earlier age. In 2009, the American College of Gastroenterology suggested that patients who smoke might warrant screening at an earlier age, perhaps at 45 years, for average risk.[1]

Risk associated with smoking develops somewhere in the 20 pack-year range, so it is incredibly important to counsel adolescents and young adults about prevention or smoking cessation.

This risk extends past cessation of smoking. Stopping smoking shows a risk reduction, but risk extends for 20-30 years after stopping smoking.[4]

Smoking is really an important and powerful risk for lots of reasons. More recently, the emphasis has been the association of serrated lesions in the right colon and smoking.

COX-2 Inhibitors and Aspirin

The COX-2 inhibitors, celecoxib and rofecoxib, were studied for prevention of recurrent polyps, showing a risk reduction of nearly three to four times as it related to the 3- and 5-year analysis for these studies[4]; but an increase in cardiovascular disease development led to the derailment of these studies. Celecoxib is still on the market; rofecoxib was removed from the market.[4]

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For primary prevention [of colorectal cancer], we know that risk reduction is evident with aspirin; risk reduction takes anywhere from 5 to 10 years with nonsteroidal anti-inflammatory drug (NSAID) use.

The US Preventive Services Task Force (USPSTF)[5] says that primary prevention for cardiovascular disease and colon cancer prevention is reasonable and recommended for patients aged 50-59 years [who have a ≥ 10% 10-year risk for cardiovascular disease]. The requisite is if you have a risk for cardiovascular disease of ≥ 10%, [primary prevention for] colon cancer gets thrown in as an added benefit. In the guideline, this is a Grade B recommendation. Use of aspirin should be discussed and recommended, provided that risks for intracranial hemorrhage or gastrointestinal bleeding are not so high as to mitigate the reduction of risk for colorectal cancer.

In patients aged 60-69 years with ≥ 10% 10-year risk for cardiovascular disease, aspirin should be considered. The guidelines gave this a Grade C recommendation. [The decision should be made on an] individual basis.

For patients older than 70 years, there is insufficient evidence to use aspirin for risk reduction based on longevity. Remember that it takes 5-10 years to begin to see a benefit [with NSAID use], so starting at that age does not make sense.

There is also insufficient evidence to recommend aspirin for primary prevention in patients younger than 50 years.

The dose of aspirin seems to be around 81 mg—that is the cardiovascular preventive dose used in the United States. The risk for NSAID-related complications increases with dose. It makes sense that a small dose with regular use may decrease the risk for recurrent lesions and also be effective for primary prevention for advanced neoplasms and nonadvanced neoplasms.

Diet

What about diet?

Fiber

There are lots of reasons why fiber may be of some benefit, perhaps with bowel fluidity and constipation. The Nurses' Health Study and the Health Professionals Follow-Up Study found that dietary fiber intake was not associated with risk reduction. Prospective studies on risk reduction for colorectal polyps and recurrent polyps have found no increased benefit with high fiber. High fiber does not seem to reduce risk for recurrent polyps.[4]

Red Meat

Risk and red meat consumption is somewhat controversial. Minimizing red meat has shown a risk reduction in some of the database analyses. The Nurses' Health Study didn't show so much of a benefit here.[4] Very recently, data from the United Kingdom Women's Cohort Study[6] found no evidence of risk associated with red meat.

There is some variance, though. Subgroup analyses showed that risk was particular to the preparation of the red meat. Use of high temperatures or prolonged duration (ie, frying, grilling, or broiling at high temperatures) may be associated with development of mutagenic, heterocyclic amines, which may interact with amino acids and lead to colorectal neoplasia.[4]

A high consumption of red meat is not good for lots of reasons. Reduction of red meat makes sense, though there is not quite the strong emphasis here. It is the same for fats and other proteins. Some studies have shown that there is a benefit.[4] You cannot stand on this one too hard with your patients, but again, it makes some sense for global health reasons.

Calcium and Vitamin D

Calcium has been proposed to reduce the risk for colorectal cancer by binding to toxic bile acids and increasing the insoluble salts. Calcium may reduce proliferation, stimulate differentiation, or induce apoptosis in the colon mucosa.[4]

The Nurses' Health Study and the Health Professionals Follow-Up Study found that calcium did not reduce risk in the proximal colon [but did reduce risk in the distal colon]. Calcium intake was in the range of 700-800 mg/day, which seems to be the upper limit of the threshold. Beyond that, supplemental calcium does not seem to increase risk reduction.[4] The data are not all that strong. Patients should take calcium if they need it. There is not a major risk reduction as it relates to calcium.

The benefit of vitamin D is somewhat subject to how the studies have been done. The Nurses' Health Study prospectively evaluated vitamin D at 400 IU/day. This is a very nominal dose that increases the vitamin D level by about 3 ng/mL.[4] If there was any deficiency, that dose would not really bump the curve.

The threshold amount for vitamin D seems to be [that which results] in the upper quartiles of the vitamin D level—you need to be in the range of ≥ 30 ng/mL.[4] I tell my patients that they should take vitamin D. I don't routinely check vitamin D levels, but it's reasonable if there is a question. I use a dose of 2000 IU/day across the board in my patients, including those with inflammatory bowel disease and diverticular disease. Treating it adequately with a dose of 2000 IU/day seems to make sense.

Vitamins

B vitamins have been studied extensively, particularly folate. Outside of pregnancy, folate supplements generally are not recommended due to the US diet. Although there are some data on folate-deficient patients having increased risk, the recommendations are that we should not supplement folate to reduce risk for polyps or cancer.[4]

The antioxidants, vitamins A, C, and E, also have been studied for prevention of colon cancer. The bottom line is that they seem to make no difference. There are not really any data relating to risk reduction for adenomas or serrated lesions.[4]

Alcohol Intake and Obesity[4]

Regular use and heavier use [of alcohol] have been associated with an increased risk for colon cancer and advanced colon neoplasia polyps. There does not seem to be a longitudinal risk reduction analysis, and we do not have the strong emphasis of risk reduction. This has most recently been studied as it relates to serrated lesions.[7,8] It makes sense across the board to decrease alcohol for a lot of good health reasons.

Obesity is associated with an increased risk for colon cancer and advanced colon neoplastic lesions. Patterns of obesity make a difference. Risk may be increased with abdominal obesity rather than the central, truncal obesity. This abdominal obesity pattern seems to be metabolically more active as it relates to upregulation of cytokines. Reduction of risk associated with weight reduction does not seem to have been studied well enough that we can adamantly hold this up to our patients. But there are lots of good reasons that we should suggest this. Weight reduction in patients, particularly in those with abdominal obesity or body mass index ≥ 30, makes sense.

Take-Away Messages

When you talk to your patients and they ask, "What can I do?", tell them to stop smoking—no question. There is ample evidence that that reduces risk, particularly for adenomas, serrated lesions, and colon cancer.

For NSAIDs, [follow] the USPSTF recommendations for low-dose aspirin for primary prevention.

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I think vitamin D is probably reasonable to recommend. Red meat is controversial; the evidence is not strong. Weight reduction makes sense. Alcohol reduction makes sense. For calcium and vitamin supplements with antioxidants, A, C, and E, there are not a lot of data.

Hopefully, this discussion will give you a format of evidence-based recommendations for your patients.

This is Dr David Johnson. Thanks again for listening.

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