Smoking causes colon cancer

Smoking and Colon Cancer

Quitting smoking will help decrease your risk for developing colon cancer.

Smoking is the leading cause of preventable death in the United States. Each year, about 443,000 Americans die from smoking or exposure to second-hand smoke. Still, almost 50 million Americans choose to smoke cigarettes. Even brief exposure to smoke can be dangerous. One cigarette contains over 600 ingredients, 4,000 chemicals and 50 cancer-causing agents and many poisonous toxins.

Dangers of Smoking

Cigarettes don’t just put you at higher risk for lung cancer. Smoking makes you more susceptible to heart disease, stroke, chronic bronchitis, emphysema, narrowing of the arteries, peripheral vascular disease, abdominal aneurysm and at least 17 types of cancer. When you choose to smoke, you are also increasing your risk for osteoporosis, infertility, pre-term delivery, low birth weight and sudden infant death syndrome.

Cellular Damage and Free Radicals

The birth and death of body cells occurs continuously. It is a normal, healthy process which allows the body to repair and replace cells. This is how cuts heal and how we recover from illness. The carcinogens in cigarette smoke damage the cells in the body and, over time, the body cannot repair the damage. As cellular damage increases and the body’s ability to repair the cells decrease, the risk for cancer goes up.

“Free radicals” is a term for damaged cells that can cause problems in the body. They are “free” because they are missing a critical molecule. They will seek to pair with another molecule, but may injure the cell’s DNA in the process. This can start a long chain of mutations. Mutated cells can grow and reproduce rapidly, and this is how disease begins.

External toxins like cigarette smoke are “free radical generators.” Cigarette smoke can overwhelm the body’s natural free-radical defense. Over time, the body cannot sustain the attack of free radicals and diseases like heart disease and cancer can develop.

How Smoking is Directly Linked to Colon Cancer

When you smoke, you are increasing your risk for colon cancer. Inhaling chemicals and toxins into your body invites free radicals to damage DNA and mutate healthy cells. Free radicals can cause the development of precancerous polyps in the large intestine, which can become cancerous and eventually cause colon cancer. Smoking can also cause more aggressive polyps known as flat adenomas, and these can be present in both light and heavy smokers.

Not only do smokers have a higher risk of developing colon cancer, they have an increased risk of dying from the disease. According to a study, people who have smoked are 23 percent more likely to die or have their cancer return within three years than nonsmokers who had colon surgery. Also, people who smoked at the time of colon cancer diagnosis are 47 percent more likely to have a recurrence of colon cancer or to die from the disease.

Family history has a significant influence on whether you are at higher risk for colon cancer. However, there is enough evidence to support that smoking puts you at equal risk for developing colon cancer as having a first-degree relative with colon cancer. Why would you allow a habit like smoking to increase your risk?

Smoking and Early Screening

Currently, the American Cancer Society recommends screening at the age of 40 for all individuals with a first-degree relative with colon cancer. However, they do not recommend earlier screenings for smokers. Someday, smoking may be seen as a risk factor that requires early screening, but you should talk to your doctor about early screening if you smoke.

Make a Plan to Quit Smoking

If you currently smoke or recently quit smoking, there is good news. Quitting smoking will help decrease your risk for developing colon cancer. There is a lag time before the risk though. Just as it takes a period of time for disease to set in, it takes equally long for the body to return to average risk. What is strongly linked with colon cancer is smoking in your teens and 20s because there is a 30-year lag period between the onset of smoking and the development of cancer.

If you are a smoker, get help quitting smoking. The American Cancer Society has effective programs to help you quit smoking and take a step toward a cancer-free life. Every body system will improve when you make this important choice. For helpful resources on how to quit smoking, visit the American Cancer Society’s website.

Colorectal Cancer Risk Factors

A risk factor is anything that affects your chance of getting a disease such as cancer. Different cancers have different risk factors. Some risk factors, like smoking, can be changed. Others, like a person’s age or family history, can’t be changed.

But having a risk factor, or even many, does not mean that you will get the disease. And some people who get the disease may not have any known risk factors.

Researchers have found several risk factors that might increase a person’s chance of developing colorectal polyps or colorectal cancer.

Colorectal cancer risk factors you can change

Many lifestyle-related factors have been linked to colorectal cancer. In fact, the links between diet, weight, and exercise and colorectal cancer risk are some of the strongest for any type of cancer.

Being overweight or obese

If you are overweight or obese (very overweight), your risk of developing and dying from colorectal cancer is higher. Being overweight (especially having a larger waistline) raises the risk of colon and rectal cancer in both men and women, but the link seems to be stronger in men.

Physical inactivity

If you’re not physically active, you have a greater chance of developing colon cancer. Being more active can help lower your risk.

Certain types of diets

A diet that’s high in red meats (such as beef, pork, lamb, or liver) and processed meats (like hot dogs and some luncheon meats) raises your colorectal cancer risk.

Cooking meats at very high temperatures (frying, broiling, or grilling) creates chemicals that might raise your cancer risk. It’s not clear how much this might increase your colorectal cancer risk.

It’s not clear if other dietary components (for example, certain types of fats) affect colorectal cancer risk.

Smoking

People who have smoked tobacco for a long time are more likely than non-smokers to develop and die from colorectal cancer. Smoking is a well-known cause of lung cancer, but it’s linked to a lot of other cancers, too. If you smoke and want to know more about quitting, see our Guide to Quitting Smoking.

Heavy alcohol use

Colorectal cancer has been linked to moderate to heavy alcohol use. Limiting alcohol use to no more than 2 drinks a day for men and 1 drink a day for women could have many health benefits, including a lower risk of many kinds of cancer.

Colorectal cancer risk factors you cannot change

Being older

Your risk of colorectal cancer goes up as you age. Younger adults can get it, but it’s much more common after age 50.

A personal history of colorectal polyps or colorectal cancer

If you have a history of adenomatous polyps (adenomas), you are at increased risk of developing colorectal cancer. This is especially true if the polyps are large, if there are many of them, or if any of them show dysplasia.

If you’ve had colorectal cancer, even though it was completely removed, you are more likely to develop new cancers in other parts of the colon and rectum. The chances of this happening are greater if you had your first colorectal cancer when you were younger.

A personal history of inflammatory bowel disease

If you have inflammatory bowel disease (IBD), including either ulcerative colitis or Crohn’s disease, your risk of colorectal cancer is increased.

IBD is a condition in which the colon is inflamed over a long period of time. People who have had IBD for many years, especially if untreated, often develop dysplasia. Dysplasia is a term used to describe cells in the lining of the colon or rectum that look abnormal, but are not true cancer cells. They can change into cancer over time.

If you have IBD, you may need to start getting screened for colorectal cancer when you are younger and be screened more often.

Inflammatory bowel disease is different from irritable bowel syndrome (IBS), which does not increase your risk for colorectal cancer.

A family history of colorectal cancer or adenomatous polyps

Most colorectal cancers are found in people without a family history of colorectal cancer. Still, nearly 1 in 3 people who develop colorectal cancer have other family members who have had it.

People with a history of colorectal cancer in a first-degree relative (parent, sibling, or child) are at increased risk. The risk is even higher if that relative was diagnosed with cancer when they were younger than 45, or if more than one first-degree relative is affected.

The reasons for the increased risk are not clear in all cases. Cancers can “run in the family” because of inherited genes, shared environmental factors, or some combination of these.

Having family members who have had adenomatous polyps is also linked to a higher risk of colon cancer. (Adenomatous polyps are the kind of polyps that can become cancer.)

If you have a family history of adenomatous polyps or colorectal cancer, talk with your doctor about the possible need to start screening before age 45. If you’ve had adenomatous polyps or colorectal cancer, it’s important to tell your close relatives so that they can pass along that information to their doctors and start screening at the right age.

Having an inherited syndrome

About 5% of people who develop colorectal cancer have inherited gene changes (mutations) that cause family cancer syndromes and can lead to them getting the disease.

The most common inherited syndromes linked with colorectal cancers are Lynch syndrome (hereditary non-polyposis colorectal cancer, or HNPCC) and familial adenomatous polyposis (FAP), but other rarer syndromes can increase colorectal cancer risk, too.

Lynch syndrome (hereditary non-polyposis colon cancer or HNPCC)

Lynch syndrome is the most common hereditary colorectal cancer syndrome. It accounts for about 2% to 4% of all colorectal cancers. In most cases, this disorder is caused by an inherited defect in either the MLH1 or MSH2 gene, but changes in other genes can also cause Lynch syndrome. These genes normally help repair DNA that has been damaged.

The cancers linked to this syndrome tend to develop when people are relatively young. People with Lynch syndrome can have polyps, but they tend to only have a few. The lifetime risk of colorectal cancer in people with this condition may be as high as 80%, but this depends on which gene is affected.

Women with this condition also have a very high risk of developing cancer of the endometrium (lining of the uterus). Other cancers linked with Lynch syndrome include cancer of the ovary, stomach, small intestine, pancreas, kidney, prostate, breast, brain, ureters (tubes that carry urine from the kidneys to the bladder), and bile duct.

For more on Lynch syndrome, see What Causes Colorectal Cancer?, Can Colorectal Cancer Be Prevented?, and Family Cancer Syndromes.

Familial adenomatous polyposis (FAP)

FAP is caused by changes (mutations) in the APC gene that a person inherits from his or her parents. About 1% of all colorectal cancers are caused by FAP.

In the most common type of FAP, hundreds or thousands of polyps develop in a person’s colon and rectum, often starting at ages 10 to 12 years. Cancer usually develops in 1 or more of these polyps as early as age 20. By age 40, almost all people with FAP will have colon cancer if their colon hasn’t been removed to prevent it. People with FAP also have an increased risk for cancers of the stomach, small intestines, pancreas, liver, and some other organs.

There are 3 sub-types of FAP:

  • In attenuated FAP or AFAP, patients have fewer polyps (less than 100), and colorectal cancer tends to occur at a later age.
  • Gardner syndrome is a type of FAP that also causes non-cancer tumors of the skin, soft tissue, and bones.
  • Turcot syndrome is a very rare inherited condition in which people have a higher risk of many adenomatous polyps and colorectal cancer, as well as brain cancer. There are actually 2 types of Turcot syndrome:

Rare inherited syndromes linked to colorectal cancer

  • Peutz-Jeghers syndrome (PJS): People with this inherited condition tend to have freckles around the mouth (and sometimes on their hands and feet) and a special type of polyp called hamartomas in their digestive tracts. These people are at a much higher risk for colorectal cancer, as well as other cancers, and they usually are diagnosed at a younger than usual age. This syndrome is caused by mutations in the STK11 (LKB1) gene.
  • MYH-associated polyposis (MAP): People with this syndrome develop many colon polyps. These will almost always become cancer if not watched closely with regular colonoscopies. These people also have an increased risk of other cancers of the GI (gastrointestinal) tract and thyroid. This syndrome is caused by mutations in the MYH gene (which is involved in “proofreading” the DNA and fixing any mistakes) and often leads to cancer at a younger age.

Since many of these syndromes are linked to colorectal cancer at a young age and also linked to other types of cancer, identifying families with these inherited syndromes is important. It lets doctors recommend specific steps such as screening and other preventive measures when the person is younger. Information on risk assessment, and genetic counseling and testing for these syndromes can be found in Genetic Testing, Screening, and Prevention for People with a Strong Family History of Colorectal Cancer.

Your racial and ethnic background

African Americans have the highest colorectal cancer incidence and mortality rates of all racial groups in the US. The reasons for this are not fully understood.

Jews of Eastern European descent (Ashkenazi Jews) have one of the highest colorectal cancer risks of any ethnic group in the world.

Having type 2 diabetes

People with type 2 (usually non-insulin dependent) diabetes have an increased risk of colorectal cancer. Both type 2 diabetes and colorectal cancer share some of the same risk factors (such as being overweight and physical inactivity). But even after taking these factors into account, people with type 2 diabetes still have an increased risk. They also tend to have a less favorable prognosis (outlook) after diagnosis.

Factors with unclear effects on colorectal cancer risk

Night shift work

Some studies suggest working a night shift regularly may increase the risk of colorectal cancer. It’s thought this might be due to changes in levels of melatonin, a hormone that responds to changes in light. More research is needed.

Previous treatment for certain cancers

Some studies have found that men who survive testicular cancer seem to have a higher rate of colorectal cancer and some other cancers. This might be because of the treatments they have received such as radiation therapy.

Several studies have suggested that men who had radiation therapy to treat prostate cancer might have a higher risk of rectal cancer because the rectum receives some radiation during treatment. Most of these studies are based on men treated in the 1980s and 1990s, when radiation treatments were less precise than they are today. The effect of more modern radiation methods on rectal cancer risk is not clear.

Colorectal cancer risk factors

Each year, more than 140,000 Americans are diagnosed with colorectal cancer. No one knows if or when cancer in the colon or rectum will develop, but understanding the risk factors for colorectal cancer may help you take measures to reduce the likelihood of getting the disease. Patients with a higher risk should consult their doctor about when to get a colonoscopy or a stool test, which may help spot early signs of the disease.

What causes colorectal cancer?

Colorectal cancer forms when the DNA in cells in the colon or rectum develop mutations that may make them unable to control growth and division. In many cases, these mutated cells die or are attacked by the immune system. But some mutated cells may escape the immune system and grow out of control, forming a tumor in the colon or rectum.

The exact cause of colorectal cancer is not known, but certain risk factors are strongly linked to the disease, including diet, tobacco smoking and heavy alcohol use. Also, people with certain hereditary cancer syndromes or a family history of colorectal cancer have a high risk of developing the disease.

Known risk factors for colorectal cancer include:

Genetics

Family history: Although the reasons are not clear in all cases, inherited genes, shared environmental factors or a combination of these influences may increase your colorectal cancer risks. Your family history may determine when your doctor will recommend a colonoscopy to screen for colorectal cancer. For example, if your father was diagnosed with colorectal cancer at 50, your doctor may recommend you get a colonoscopy at 40.

Inherited syndromes: The two most common inherited syndromes linked with colorectal cancers are familial adenomatous polyposis (FAP) and hereditary non-polyposis colorectal cancer (HNPCC). Other syndromes that may increase the risk of developing colorectal cancer include Lynch Syndrome, Turcot Syndrome and Peutz-Jeghers Syndrome.

Racial and ethnic background: African Americans have the highest incidence of colorectal cancer in the United States. Ashkenazi Jews also have a higher risk of developing the disease. If you are in one of those ethnic groups and have no other risk factors, your doctor may suggest getting a colonoscopy at age 45 rather than 50, as is recommended for most average-risk patients.

Learn more about genetic testing

Lifestyle

Diet: Diets that are high in red and processed meats (e.g., beef, lamb, hot dogs) may increase your colorectal cancer risks. Frying, grilling, broiling or other methods of cooking meats at very high temperatures create chemicals that may also contribute to an increased risk. A diet rich in fruits, vegetables and high-fiber grains may help reduce your risk of developing colorectal cancer.

Inactive lifestyle: Individuals who live a sedentary lifestyle have an increased chance of developing colorectal cancer.

Smoking: Some of the cancer-causing substances associated with smoking may be swallowed, potentially increasing the risk of developing colorectal cancer.

Alcohol use: Heavy alcohol use may lead to an increased risk of colorectal cancer.

General

Age: Although colorectal cancer may occur at any age, the chances of developing the disease may dramatically increase after the age of 45. Nearly 95 percent of all colorectal cancer cancers occur in patients 45 or older. The median age of a patient diagnosed with colorectal cancer is 68, according to the National Cancer Institute.

History of colorectal cancer or polyps: If you have had colorectal cancer before, you are more likely to develop cancer in other areas of the colon and rectum. Or you may experience a recurrent cancer, which is a malignancy that reappears at or near the same location as the original tumor. You may also be at a higher risk of colorectal cancer if your doctor found polyps during a colonoscopy, even if those polyps were removed and/or benign.

History of inflammatory bowel disease (IBD): Having IBD, including ulcerative colitis and Crohn’s disease, may increase your chances of developing colorectal cancer. Your risk may be higher the longer you have experienced IBD and depending on how much of your colon is affected.

Obesity: Being overweight may increase your risk of developing colorectal cancer.

Type II diabetes: This condition is associated with a higher risk of rectal cancer. It may also affect your prognosis.

Next topic: What are the symptoms of colorectal cancer?

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The latest U.S. Surgeon General’s report on smoking and health reveals that the health consequences of smoking go far beyond lung cancer and cardiovascular disease. It links smoking with diabetes, colorectal and liver cancer, rheumatoid arthritis, erectile dysfunction and age-related macular degeneration. It also concludes that inhaling secondhand smoke can lead to increased risk of stroke in nonsmokers.

The surgeon general recently reported that in the last 50 years, eight million lives have been saved as a result of tobacco control measures. Unfortunately, today’s smokers have a higher risk of lung cancer than smokers faced back in 1964 when the first report was issued, even though they smoke fewer cigarettes. This may be the consequence of changes in the way cigarettes are made and the chemicals they now contain, according to Acting Surgeon General Boris Lushniak, M.D., M.P.H.

The report found that women today are dying at the same rate as men from smoking-related diseases, including lung cancer, chronic obstructive pulmonary disease (COPD) and heart disease. The death rate from COPD is now higher in women than in men.

The statistics on smoking revealed in the report are grim. Approximately 5.6 million American children alive today – one out of 13 youngsters under age 18 – will die prematurely from smoking-related diseases unless current smoking rates drop. Over the last 50 years, more than 20 million Americans have died as a result of smoking. Cigarette smoking is still killing nearly a half million Americans per year, with over 16 million more suffering from smoking related conditions.

Here’s some more bad news from the report: each day another 3,200 children under age 18 smoke their first cigarette, and another 2,100 youth and young adults become daily smokers. The sad fact is that every adult who dies prematurely from smoking is replaced by two young adult smokers.

Andrew Weil, M.D.

Smoking increases risk of bowel cancer in women

BBC News has revealed that, “Women who smoke have a higher risk of cancer than men,” reporting the results of a new study examining the relationship between gender and bowel cancer caused by smoking.

The large-scale study found that smoking increased the risk of bowel cancer in women by 19% compared with women who had never smoked. This was much larger than the (non-significant) 8% risk increase seen in male smokers.

Smoking is a recognised risk factor for bowel (colon) cancer and several other life-threatening diseases in both men and women. It is important to bear in mind that this research only looked at colon cancer. Whether there are gender differences in other smoking-related cancers, such as lung cancer, is uncertain based on the findings of this study alone.

The authors point out that their study did not take into account important risk factors known to be linked to bowel cancer, such as family history, diet, and alcohol consumption. If these had been accounted for the results may well have been different.

The study also didn’t produce any firm evidence to explain why there may be a difference in risk between women and men. Future research will need to address these limitations to see if the gender differences in risk still apply and, if so, why.

Where did the story come from?

The study was carried out by researchers from the University of Tromsø, Norway in collaboration with researchers from institutions in Hawaii and Finland, and was funded by the Norwegian Cancer Society.

It was published in the peer-reviewed journal Cancer Epidemiology, Biomarkers and Prevention.

The BBC’s coverage was generally accurate, although it wasn’t initially obvious that the study only related to bowel cancer rather than all cancers, which readers may have assumed from the headline.

The BBC also discussed a second recent study (also covered by the Mail Online website) that reportedly showed how teenage girls exposed to passive smoking had lower levels of the “good” form of cholesterol that reduces heart disease risk. This, the BBC reported, gave a possible explanation as to why women who start smoking increase their risk of a heart attack.

What kind of research was this?

The researchers reported how smoking is a recently established risk factor for what medical professionals refer to as colon cancer, or cancer of the large bowel. They explained that the levels of colon cancer in Norwegian women are unusually high when compared with similar countries.

In men, smoking levels peaked during the late 1950s, while in women levels did not peak until the 1970s. The fact that historically women smoked less but still had high levels of colon cancer could mean they were more vulnerable to the harmful effects of smoking in terms of colon cancer risk.

To test this, the researchers carried out a cohort study to see if women may be more susceptible to smoking-related colon cancer than men.

What did the research involve?

The researchers recruited 602,242 Norwegians who were aged 19 to 67 at enrolment between 1972 and 2003.

They combined the information gathered from four separate cohort studies into one larger study. The researchers linked unique IDs assigned to each of the study participants to National Cancer Registry databases so they could establish whether any of the study group developed cancer.

At enrolment, and at various other points throughout the study period, participants filled out multiple questionnaires about a wide range of health and lifestyle behaviours, such as smoking, diet and physical activity levels, as well as demographic information.

Smoking levels were categorised into two main groups for analysis:

  • those who had never smoked (never-smokers)
  • a pooled group of current smokers and ex-smokers (ever-smokers)

The main analysis looked at how the two levels of smoking influenced the risk of developing colon cancer overall, as well as specific subgroups of colon cancer. That is, whether the cancer was located in the first part of the colon (proximal colon cancer) or lower parts of the colon (distal colon cancer).

The main analysis took account of age at enrolment, level of physical activity, body mass index (BMI) and years of education. These represented factors known to influence the risk of developing colon cancer (confounders).

What were the basic results?

The study followed people for an average of 14 years, during which time 3,998 people (46% women) developed colon cancer.

Women categorised in the groups who started smoking the earliest, smoked for longest, or smoked the most cigarettes per day were at more than 20% higher risk of colon cancer (range 28-48%) than women never-smokers.

The increase in risk was much larger for proximal colon cancer, with female ever-smokers more than 40% more at risk of developing the disease compared with female never-smokers.

The researchers also tested for differences in the findings between men and women. They found this was only the case for the association between female ever-smokers and the risk of proximal colon cancer.

How did the researchers interpret the results?

The researchers concluded that their findings meant that, “Female smokers may be more susceptible to colon cancer, and especially to proximal colon cancer, than male smokers.”

Conclusion

In this study, the researchers suggest that smoking played a role in increasing the risk of colon cancer in both sexes, but it seemed to play more of a role in women smokers. This particularly increased the risk of cancer of the first part of the large bowel (proximal colon cancer).

The study had many strengths, including its large size and long follow-up time. However, the research suffers from some limitations, meaning that we can’t be sure that women smokers really do have a higher risk of colon cancer based on this study alone.

These limitations include:

  • The study did not take account of many factors known to increase the risk of colon cancer, such as higher alcohol and red meat consumption. Had it done so, the results may have been different. The researchers point out that, generally, alcohol and red meat consumption is higher in men, putting them at an increased risk of colon cancer. Not taking these factors into account means it was less likely to find the results they did.
  • The study only looked at colon cancer. This tells us nothing about whether women smokers are more susceptible than men to other types of cancers. This would need direct investigation.
  • Smoking was categorised into only two groups rather than a more detailed breakdown, and did not account for passive smoking levels. There will therefore have been some error in using this simple categorisation method.

Overall, the study suggests the effect of smoking on the risk of developing colon cancer may differ by gender, but it cannot confirm this is definitely the case, or explain why this may be. Further research is required to confirm both of these questions.

Analysis by Bazian. Edited by NHS Choices. Follow Behind the Headlines on Twitter.

Analysis by Bazian
Edited by NHS Website

Links to the headlines

Smoking ‘poses bigger risk to women’

BBC News, 1 May 2013

Links to the science

Parajuli R, Bjerkaas E, Tverdal A, et al.

The Increased Risk of Colon Cancer Due to Cigarette Smoking May Be Greater in Women than Men

Cancer Epidemiology Biomarkers Prevention. Published online April 30 2013.

Most people understand the link between smoking and lung cancer, but researchers are learning even casual smokers are increasing their risk for other cancer types as well.

Case in point: Smoking increases the risk for developing colorectal cancer, and female smokers may have a greater risk than male smokers, according to data published in Cancer Epidemiology, Biomarkers & Prevention, a journal of the American Association for Cancer Research.

Dr. Inger Torhild Gram, professor in the Department of Community Medicine at the University of Tromsø in Norway, wanted to know why the number of new colon cancer cases per year has exploded during the last 50 years for men and women.

During her study she and her colleagues found startling new evidence to suggest women who smoke less than men still get more colon cancer.

“The finding that women who smoke even a moderate number of cigarettes daily have an increased risk for colon cancer will account for a substantial number of new cases because colon cancer is such a common disease,” said Gram in a written statement.

National Cancer Report: Fewer Dying, But News isn’t All Good

Women Smokers Have Higher Risk of Squamous Cell Skin Cancer
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“A causal relationship between smoking and colorectal cancer has recently been established by the International Agency for Research on Cancer of the World Health Organization, but unfortunately, this is not yet common knowledge, neither among health personnel nor the public,” she said.

The American Cancer Society estimates that 142,820 people will be diagnosed with colon cancer in 2013 and that 50,830 will die from colon cancer in the United States.

It’s important to note that while colorectal cancer can be extremely deadly, it’s also one of the most preventable cancer types.

If everyone who is 50 years old or older were regularly screened for colorectal cancer, as many as 60 percent of deaths from this cancer could be avoided, according to the NCI.

To examine the association between cigarette smoking and colon cancer, by tumor location, Gram and her colleagues looked at data for a large Norwegian study of more than 600,000 men and women.

The participants from four surveys initiated by the National Health Screening Service of the Norwegian Institute of Public Health had a short health exam and completed questionnaires about smoking habits, physical activity and other lifestyle factors.

The participants were followed by linkage to the Cancer Registry of Norway and the Central Population Register. During an average 14 years of follow-up, close to 4,000 new colon cancer cases were diagnosed.

Gram and her colleagues found, for the first time, that female smokers had a 19 percent increased risk compared with never-smokers, while male smokers had an 8 percent increased risk compared with never-smokers.

In addition, women who started smoking when they were 16 or younger and women who had smoked for 40 years or more had a substantially increased risk, by about 50 percent.

The study also show the number of cigarettes smoked per day, number of years smoked and number of pack-years smoked increased a woman’s colon cancer risk more than men.

Smoking Increases Colon Cancer Risk

Smoking causes many types of illnesses — including some that people may not immediately associate with cigarettes, such as colon cancer. Smokers not only have a higher risk of developing colon cancer, they also have a higher risk of dying from the disease.

Colon Cancer: The Smoking Connection

“Cigarette smoke contains many carcinogens , benzopyrenes being the most well-known,” says Thomas Imperiale, MD, professor of medicine and associate director for research for the Division of Gastroenterology at the Indiana University School of Medicine. “It’s believed that these carcinogens cause damage to the DNA and, over time, the body’s ability to repair that damage decreases.”

Colon Cancer: Does Quitting Reduce Risk?

Breaking your smoking habit is always a good idea in terms of cancer prevention. But, while quitting can help reduce your risk of developing colon cancer, there is a long lag time before the risk drops, says Dr. Imperiale. “There’s an ‘induction’ period, too,” he explains. “What’s been strongly linked with cancer is smoking in your teens and 20s, because there’s about a 30-year lag between the onset of smoking and the onset of adenocarcinomas” — pre- or early cancer. So, just as it takes a long period for the cancer to show up, it can take an equally long time for the body to return to the average level of risk.

Colon Cancer: Screening for Smokers

At present, there’s no set guideline for when smokers should be screened for colon cancer if they have no other apparent risk factors. The American Cancer Society (ACS) guidelines suggest that seemingly healthy people who are at low risk for developing colon cancer should be screened starting around age 50; how often after that you would have your next colonoscopy screening depends on results of that first test.

Imperiale says that the evidence is strong enough to indicate that the risk of colon cancer from smoking is as high as having a first-degree relative — parent, sibling, or child — with colon cancer. The ACS recommends that those people begin screening at age 40, but does not recommend the same for smokers or former smokers. Unfortunately, “for some reason, we’ve been skirting the issue of screening these people more aggressively,” he says.

As more research is done on the link between smoking and colon cancer, smoking may become recognized as a risk factor that should prompt earlier screening. Until that happens, if you are or were a smoker, talk to your doctor about whether you are a candidate for earlier testing.

Keep in mind that it’s never too late to quit smoking. According to Imperiale, “If a smoker does quit the habit, although it takes time for the body to return to its ability to repair damaged DNA, it does happen over time.”

The Association between Cigarette Smoking and Risk of Colorectal Cancer in a Large Prospective Cohort from the United States

Materials and Methods

Participants were drawn from the Cancer Prevention Study II (CPS-II) Nutrition Cohort (hereafter called the Nutrition Cohort), a prospective study of cancer incidence and mortality among 184,187 men and women from the United States, that is described in detail elsewhere (21). Briefly, the Nutrition Cohort is a subgroup of the ∼1.2 million participants in the CPS-II, a prospective mortality study established by the American Cancer Society in 1982. Participants in the larger study were recruited nationwide and completed only the single questionnaire at enrollment.

Members of the CPS-II mortality cohort who resided in 21 states with population-based state cancer registries and were 50 to 74 years of age in 1992 were invited to participate in the Nutrition Cohort. Upon entry, participants completed a mailed questionnaire on demographic, medical, behavioral, environmental, occupational, and dietary factors. Follow-up questionnaires were sent to cohort members in 1997, 1999, 2001, 2003, and 2005 to update exposure information and to ascertain newly diagnosed health problems, including cancer. The response rate among living participants for each of the follow-up questionnaires (after multiple mailings) was at least 89%. For the present study, the follow-up period ended on June 30, 2005. All aspects of the CPS-II Nutrition Cohort study were approved by the Emory University Institutional Review Board.

A total of 86,402 men and 97,785 women participated in the Nutrition Cohort. From this population, we excluded 10,129 (11.7%) men and 13,501 (13.8%) women who reported any prevalent cancer at baseline, with the exception of nonmelanoma skin cancer; 2,864 (3.3%) men and 2,795 (2.9%) women who were lost to follow-up; 1 man and 1 woman who reported being diagnosed 180 or more days prior to the verified diagnosis date; 16,526 (19.1%) men who reported ever having smoked pipes or cigars; and 2,972 (3.4%) men and 4,584 (4.7%) women who had missing or uninterpretable smoking data on their baseline questionnaire. Individuals were considered to be lost to follow-up if they did not return any of the questionnaires after baseline and were not identified as deceased prior to December 31, 1997.

We used Cox-proportional hazards models to examine the association between cigarette smoking and incident colorectal cancer after stratifying by single year of age and adjusting for potential risk factors with time since enrollment as the underlying time metric. Individuals contributed person-time to the analysis until they were diagnosed with colorectal cancer or were censored (i.e., died of causes other than colorectal cancer, reached the end of follow-up, failed to return a follow-up questionnaire, provided incomplete information on smoking habits on a follow-up questionnaire, reported unverified colorectal cancer, or were diagnosed with nonadenocarcinoma colorectal cancer or colorectal cancer in situ). If a participant did not return a questionnaire, or if they reported unverified colorectal cancer on a questionnaire, they were then censored 1 day after their return of the previous questionnaire. After all exclusions, 51,365 men and 73,386 women were included in the analysis.

A total of 1,962 verified incident cases of invasive colorectal cancer (1,006 men, 956 women) were identified between the time of enrollment in 1992/1993 and June 30, 2005. Self-reported cases were verified from medical records (n = 1,227) or through linkage to state cancer registries (n = 422). Additional cases (n = 313) were identified through linkage with the National Death Index, with all but 70 of the cases able to be linked to state cancer registries to obtain a date of diagnosis. These 70 colorectal cancer deaths were included as incident cases with the date of diagnosis assigned as the date of death. Incident cases of colorectal cancer were identified by ICD-9 codes 153-154.1 or by ICD-10 codes C18-C20.9. As discussed above, in situ cases were censored at the date of diagnosis, as were nonadenocarcinoma colorectal cancers, defined by ICD-9 histology codes as <8,140 and >8,574.

Cigarette smoking status (“never”, “former”, “current”) was ascertained at enrollment in 1992/1993, and was updated in successive questionnaires. At baseline, participants were defined as a lifelong nonsmoker if they indicated having smoked fewer than 100 cigarettes in their lifetime. Participants were designated as current smokers if they reported smoking at the time of the questionnaire or as former smokers if they reported having successfully quit prior to the questionnaire. Smoking status was reassessed in questionnaires administered in 1997, 1999, 2001, and 2003. The 1999, 2001, and 2003 questionnaires requested only information on current smoking status (“Do you currently smoke cigarettes”) and on the number of cigarettes currently smoked per day. Former smokers and continuing lifelong nonsmokers were therefore classified as such based on answers to previous questionnaires.

The information on smoking status was inconsistent for 1,813 men (3.5%) and 3,731 women (5.1%) who reported never having smoked on a follow-up questionnaire after previously reporting current or former smoking. These participants were considered to be former smokers rather than lifelong nonsmokers in time-dependent analyses. Individuals who, on the 1999 (n = 43), 2001 (n = 34), or 2003 (n = 58) questionnaire, indicated being a current smoker, but did not indicate current daily cigarette consumption and had reported being a lifelong nonsmoker in all previous questionnaires were considered to be lifelong nonsmokers under the assumption that they checked the wrong box.

The age at initiation at baseline for all current and former smokers was determined by combining information from the 1982 CPS-II questionnaire (returned by all participants in the Nutrition Cohort) and the 1992/1993 questionnaire. All other variables of smoking were treated as time-dependent variables.

We constructed a time-varying model to examine the association between smoking status (never, current, former) and incident colorectal cancer. Additional time-varying models comparing current smokers to lifelong nonsmokers examined increasing levels of cigarette smoking duration (<40, 40-49, >50 y), years since cessation (<40, 40-49, >50 y), and years since smoking initiation (<40, 40-49, >50 y). Analyses of former smokers examined how age at quitting (<40, 40-49, 50-59, and >60), and years since cessation (>30, 30-21, 20-11, 10-1 y) modified risk compared with lifelong nonsmokers. Each measure of exposure was assessed using sex-specific models as well as models with both sexes combined. Trend tests were obtained for increasing levels of smoking by assigning an ordinal value to each successive level and reporting the resulting P value. Nonsmokers were not included in the test for trend.

Multivariate models were adjusted for known and putative risk factors for colorectal cancer. These potential confounders were body mass index (<18.5, 18.5-24.9, 25-29.9, >30 kg/m2, missing), educational attainment (some high school, high school/vocational school graduate, some college, college graduate, graduate school, missing), family history of colorectal cancer (yes, no), physical activity (quartiles, in metabolic equivalents (METs), missing), race (white, other), multivitamin use (current user, not current user, missing), aspirin use (no use, 1-14, 15-29, 30-59, >60 pills per month, missing), alcohol use (nondrinker, <1, 1, >1 to 2, >2 to 3, >3 drinks/d, missing), vegetable consumption (quartiles, missing), red and processed meat consumption (quartiles, missing), and history of colorectal endoscopy (ever, never, missing). Models that combined men and women also controlled for sex, and models including women were controlled for estrogen-only hormone replacement therapy use (never, current, former, missing), estrogen and progesterone combined hormone replacement therapy (never, current, former, missing) and “other” hormone replacement therapy (yes, no, missing). All covariate values were based on information obtained at enrollment with the exception of multivitamin use, aspirin use, alcohol use, hormone replacement therapy use, and history of endoscopy which were updated during follow-up. History of endoscopy use was not ascertained until the 1997 questionnaire; therefore participants were considered to have missing endoscopy information for the period 1992 to 1997. Alcohol use during the last 4 y of follow-up was based on the 1999 questionnaire.

Review Article
Cigarette Smoking and Colorectal Cancer: From Epidemiology to Bench

Colorectal cancer is the third most commonly diagnosed malignancy in the world. The risk factors include inherited genetic mutations and environmental elements such as a high-fat diet, low-fiber diet and sedentary lifestyle. Cigarette smoking is a serious worldwide health problem and the leading cause of preventable death. Although smoking increases the risk of cardiovascular disease and various cancers such as lung, oral and some gastrointestinal cancers, smoking is currently not recognized as a risk factor of colorectal cancer by either the International Agency for Research on Cancer (IARC) or the US Surgeon General. Accumulating epidemiological studies indicate that cigarette smoking is positively correlated to colorectal adenomatous polyps, and positive associations between cigarette smoking and colorectal cancer risk have been reported. Long-term cigarette smoking increases the risk of colorectal cancer mortality and the likelihood of a mutation occurring in the adenomatous polyposis coli (APC) tumor suppressor gene, which has a “gatekeeper” function in the colonic mucosa. Heavy smoking is associated with an increased risk of obtaining a mutation in BRAF, but not KRAS. Current and long-term smokers are at elevated risk of microsatellite instability high (MSI-H) colorectal cancers and an estimated one in five MSI-H colorectal cancers is attributable to cigarette smoking. Nicotine and its metabolite, 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK), are two of the most causal elements for smoking-related cancers. Nicotine and NNK have been shown to induce colon cancer growth and even enhance the migration of colon cancer cells, which is a major cause of cancer death. In conclusion, cigarette smoking should be considered a risk factor of colorectal cancer.

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