Patrick Lynch, M.D.
Professor
Gastroenterology, Hepatology and Nutrition
The University of Texas MD Anderson Cancer Center
Good day! I'm Patrick Lynch. I'm a gastrointestinal endoscopist here at The University of Texas MD Anderson Cancer Center. And today I'll be talking to you about common risk factors for malignancy.
The objectives of this unit will be to enable you to identify risk factors that are common for cancer, including environmental, occupational, infectious, and biological. We'll also identify risk factors for specific cancers. And we'll conclude by talking about family history as a risk factor for certain malignancies.
So, the definition of a cancer risk factor really is anything that increases an individual's chance of developing a cancer.
Some of these are personal risk factors, such as environmental or occupational exposures, infections or other medical conditions, medical treatments, including chemotherapy, various biological factors, and as a separate consideration, family history of malignancy.
Some of the most important considerations or risk factors for cancer have to do with lifestyle and exposure. And among these are: tobacco use, alcohol, a diet that is high in fat, and sun exposure. Less common, but important in certain situations, are workplace exposures, such as to asbestos, aromatic amines, benzene, and various other chemicals.
A fairly common category, or grouping of risk factors, has to do with infections. Some of these include viruses, such as the human papillomavirus or HPV, a known risk factor for cervical and other squamous carcinomas; the Epstein-Barr virus, hepatitis B and hepatitis C, which are important risk factors for liver cancer, hepatoma; as well as the HIV or humano --- human immunodeficiency virus. Certain bacteria are also known to increase risk of specific cancers. And among these are Helicobacter pylori, which increases the risk of stomach cancer, and chlamydia trachomatis. Certain parasites in certain countries, at least, increase risk of liver cancer. And these include liver flukes and schistosomiasis. Other medical conditions increase variably the risk for certain cancers. And among these are: inflammatory bowel disease, chronic pancreatitis, adenomatous polyps, lobular carcinoma in situ, aytop --- atypical ductal hyperplasia, polycystic ovarian syndrome, and a personal history of cancer.
Now, as we see here, the risk of cancer can be viewed as increasing in a step-wise fashion depending on the underlying risk factor. So here, for example, we see that a person with no risk factor still has a 5% risk of developing colorectal cancer at some time in their life. If they have a personal history of colorectal neoplasm, the risk increases to as much as 15 to 20%. Now, although the estimates vary quite a bit, having an underlying history of inflammatory bowel disease can increase the risk still further, perhaps to as high as 40% over the --- a person's lifetime.
Importantly, certainly in the cancer patient population, is that risk of cancer can actually be increased by treatment of certain cancers themselves. So, many forms of chemotherapy for a given cancer can actually increase the risk of developing another cancer at some time later in life. Radiation therapy itself can increase cancer risk. Certain exposures, such as diethylstilbestrol, can increase cancer risk. Commonly used agents, such as tamoxifen, are associated with an increased cancer risk as well. And, causing a lot of controversy in recent years has been the use of hormone replacement therapy in women who are post-menopausal.
Obviously, gender is an important risk factor. So men and women have certain organs that are specific to their gender, but even aside from this, gender is associated more or less with cancer risk, depending on the organ under consideration. Age is a very important risk factor for malignancy. With the exception of certain childhood illnesses, the risk of various common cancers, breast, colorectal, lung, prostate, increase with advancing age. Certain ethnic groups are disproportionately affected with cancer. Some of this is likely a genetic predisposition, but other factors are likely present as well. So, Ashkenazi Jewish patients are at risk of certain familial clusterings of breast cancer, for example. And African Americans are at increased risk for certain cancers, including, among these, prostate and colorectal cancer.
Familial risk is something that is relatively uncommon in the general population but can markedly increase the risk to a particular person if they have that specific risk factor. So multiple family members having the same type of cancer can be a clue that a familial predisposition may be present. Now, often this risk is multifactorial and is associated with a combination of shared environmental factors as well as low-penetrant genes.
Now, as we see here, the risk of certain cancers, such as colorectal cancer here, also increases step-wise, but this time in association with increasing cancer history in the family. So, as we see, having one first-degree relative increases slightly the risk of developing cancer. But, if that one relative is young at the time of diagnosis, the risk increases further. Having multiple family members affected with colorectal cancer likewise increases the risk. Note that the very highest risk is something that occurs in individuals that have a known mutation in one of the familial predisposing syndromes, in this case Hereditary Nonpolyposis Colorectal Cancer.
Now, let us go through some of the common risk factors that are associated with some of the leading malignancies in this country. So in the case of breast cancer, variation in age at menarche and menopause are associated with cancer risk. Reproductive history is important. Having had children, particularly at an early age, actually lowers one's risk of certain cancers but may actually increase the risk of other cancers. Now, a biopsy showing atypical hyperplasia in the breast is a risk factor, an important pathologic risk factor. Previous chest radiation, exposure to diethylstilbestrol, obesity, an increasingly common problem in this country, is associated with breast cancer risk. Certainly, history of hormone replacement therapy and even use of alcohol can increase risk of breast cancer. In the case of colon --- colorectal cancer, as we have already discussed, a history of underlying inflammatory bowel disease, whether Crohn's disease or ulcerative colitis, increases one's risk of developing colorectal cancer. A history of colon polyps, especially adenomas, are associated with increased risk of subsequent adenoma or even of cancer. Physical inactivity and obesity are increasingly known to be risk factors for colorectal cancer. Heavy alcohol intake increases one's risk as well, though this may be more associated with risk of rectal cancer as opposed to cancers in the more proximal colon. Smoking, likewise, is --- is associated with colorectal cancer risk, again, perhaps more so with development of rectal cancer. And diet, although interventions to modify diet have not had an impact in short term clinical trials, nevertheless, at the epidemiologic level, is a strong, perhaps the strongest overall, risk factor for colorectal cancer.
Endometrial cancer, slightly less common than breast or colorectal, is associated with a number of risk factors that are specific to it; other risk factors that it has in common with other cancers. So again, obesity, as we have seen over and over again, is a risk factor. Likewise, it is a risk factor for endometrial cancer and a very important one for endometrial cancer. Exposure to tamoxifen and estrogen therapy, particularly without the use of progesterone, increases endometrial cancer risk. Polycystic ovary kidney --- [I'm sorry] --- Polycystic ovary syndrome --- increases --- increases endometrial cancer risk. A personal history of diabetes, prior pelvic radiation, and age at menarche and menopause are important for endometrial cancer. Ovarian cancer, less common than endometrial cancer, in general, but a more aggressive malignancy, is associated also with particular reproductive histories; again, with age at menarche and menopause, and is associated with a personal history of breast cancer. And this is true whether a person has an underlying familial susceptibility, such as one of the BRCA syndromes that predisposes to both breast and ovarian cancer. As with many of these other cancers we've already seen, obesity is a risk factor as well for ovarian cancer. Pancreatic cancer, which is increasing in incidence and is a very serious cause of mortality, is less well understood in terms of the underlying risk factors. Nevertheless, a history of smoking, cirrhosis of the liver, and certain forms of chronic pancreatitis increase risk of pancreatic cancer.
Cervical cancer is not as common as it was at one time. And there are many factors associated with this. It's now fairly clearly seen that human papillomavirus exposure, certain particular genotypes of HPV, in particular, are associated with greater cervical cancer risk. As with other tumors, smoking is an important risk factor for cervical cancer. Other infections, such as HIV and chlamydia, are associated. Reproductive history, including multiple pregnancies, and this may have to do in part with multiple partners, but multiple pregnancies as well, likely increases risk. And daughters of patients who are exposed to diethylstilbestrol is still another risk factor for cervical cancer. But what about lung cancer? Lung cancer is the most common overall malignancy, certainly the most important overall cause of mortality in men and women alike. Smoking of tobacco or, to a lesser extent, marijuana is a key risk factor for lung cancer. Asbestos exposure is a risk factor not only for the rare mesothelioma but also for the much more common lung cancer. Radon exposure is an important factor as well, although fairly un --- uncommon for a given individual. And recurring lung infection, such as from old tuberculosis, may be a risk factor as well.
Moving down the list, we see that thyroid cancer is associated with previous radiation to the neck or use of radioactive iodine. Gender is also important, though not as clearly understood why that might be. And certainly women have an increased risk of the common forms of thyroid cancer. Melanoma, although it's not the most common skin cancer, is certainly the number one cause of mortality from lung [speaker intended to say "skin"] cancer around the world. And history of sunburns, particularly early age at first sunburn, rather than chronic exposure, is the key risk factor here. Dysplastic nevi is an important predisposition to melanoma. There are syndromes that run in families in which dysplastic nevi are very common, the so-called familial atypical mole in melanoma syndrome, but dysplastic nevi even occurring sporadically are an important risk factor for melanoma. Fair skin, and this may relate as well to the importance of early and severe sunlight damage, having fair skin, light hair, and freckling are related to melanoma risk. And gender, more melanoma in men, though again this may relate to the greater sun exposure that men achieve in the workplace.
So, we've seen here that there are a number of important risk factors for the common malignancies. How do we go about assessing this? Well, it's very important to take a comprehensive cancer history. One focuses on the patient's personal history, as well as the family history, and exposure to any particular risk factors, whether they be dietary, environmental, or occupational. Certain conditions may require confirmation, as through old medical records. And this is important to obtain whenever possible.
So, in a person's personal history, it's important to look at their current age, age at previous cancer diagnosis. Establish the treatment and follow-up plan with a recognition that a particular treatment may increase the patient's risk for other malignancies. Assess their symptoms, non-medical --- non-cancer medical problems, surgical history, and biopsy. Conduct appropriate cancer screening and review the medication list carefully. It's also important to look at particular exposures, such as oral contraceptives and hormone replacement therapy. And sometimes this requires a very targeted questioning of the patient. In female patients, inquire about the age at menarche and menopause, age at first pregnancy. Particularly in people that have occupational exposures, the details of the occupational exposure, the nature of the work and duration are very key. Environmental exposures we've already talked about, but, particularly, sunlight and dietary considerations are important here. Smoking and alcohol are critical. Many patients are evasive about the details of their smoking and, particularly, of alcohol history and some persistent questioning may be necessary.
Taking a cancer-focused family history is also very important, though something that tends to not be as high a priority as it could be in the course of taking a medical history. It's important to look at the types of cancers that may have occurred in the family as well as their ages of diagnosis. Because as we've already emphasized, age at diagnosis is a very key factor in underlying familial cancer syndromes. The number of affected relatives is important to document; not only how many were affected but also how many were unaffected, as some families vary considerably in size. It's important to look both at the maternal and paternal family history. So commonly, when breast cancer is the consideration in a given patient, we sometimes focus exclusively on the maternal family history, but it's certainly known that, for example, in cases of --- of BRCA syndrome, that transmission through an unaffected father can sometimes occur. It's important to extend the pedigree around each cancer diagnosis because, in this way, we gain additional information about the --- the possibility of a specific cancer predisposition. Also consider the history --- the accuracy of the historian. Some people are better historians than others and, to the extent that the patient is a poor historian, you may have to discount the information provided.
So, in documenting a family history, we have certain conventions that are used in constructing a pedigree. We identify the patient that we're interviewing with an arrow. Obtain information about their siblings and children, if they have any. Document the ages and ages at death of the parents, whenever possible, but extend that family history to include even second-degree relatives, such as aunts or uncles, as shown here.
There are certain red flags for hereditary cancer as already touched on: clustering of the same particular type of cancer in close relatives, unusually early age at cancer onset. So, breast and colorectal cancer, which are important diseases that --- that have important family and, in fact , genetic predispositions, in some cases, tend to be cancers of advancing ages, 60s, 70s, and older. So, when you have a woman with breast cancer in her 20s or 30s, or a man or woman with colorectal cancer in their 20s, 30s, or 40s, this may be a clue to the presence of an underlying inherited susceptibility. [Other red flags are] multiple primaries in a single individual, whether they be multiple cancers involving the same organs, such as bilateral cancer in paired organs, such as the breast; or multiple primaries, for example, colorectal cancer and endometrial cancer in HNPCC. And certainly if there is evidence of autosomal dominant inheritance, transmission from generation to generation through an affected parent and a family pattern that's consistent with a known syndrome. So being familiar with the --- with the known syndromes is very helpful here.
In conclusion, the cancer risk assessment should focus on a variety of key considerations: environment, occupational exposure, infectious agents, biological agents, and the like. Many exposures create a risk for more than one type of cancer. So, as we've seen, smoking and obesity are risk factors for multiple types of tumor, and family history should be a part of the cancer risk assessment for all individuals. Thank you very much. Please let us know if --- if this presentation has been helpful to you. We invite feedback from all program participants. Thank you very much.
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