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Logo of nihpaAbout Author manuscriptsSubmit a manuscriptHHS Public Access; Author Manuscript; Accepted for publication in peer reviewed journal;
Prim Care. Author manuscript; available in PMC 2010 September 1.
Published in final edited form as:
PMCID: PMC2713871

Cancer Risk Assessment for the Primary Care Physician

Larissa A. Korde, MD, MPH* and Shahinaz M. Gadalla, MD, PhD


Cancer is the second leading cause of death in the United States. Cancer risk assessment can be divided into two major categories: assessment of familial or genetic risk and assessment of environmental factors that may be causally related to cancer. Identification of individuals with a suspected heritable cancer syndrome can lead to additional evaluation and to interventions that can substantially decrease cancer risk. Special attention should also be paid to potentially modifiable cancer risk factors in the course of advising primary care patients regarding a healthy lifestyle. Clinical guidelines targeting both genetic and modifiable cancer risk factors are available, and can facilitate applying these health care principles in the primary care setting.

Keywords: cancer risk, risk assessment, genetics, family history, environmental risk factors, lifestyle

The American Cancer Society estimates that there will be 1.44 million new cases of cancer diagnosed in the United States in 2008. Breast and prostate cancer are the most common malignancies diagnosed among women and men in the US, respectively, accounting for 25% of cancer diagnoses, followed by lung and colon cancer. Cancer is the second leading cause of death in the US population overall, and the leading cause of death among men and women age 60 – 79 (1). Cancer mortality rates have declined over the past two decades, in part due to improvements in screening, which leads to detection of malignancy at an earlier and more treatable stage. A thorough assessment of cancer risk in the primary care setting, with targeted application of appropriate screening strategies, is crucial to maintaining this trend.

Cancer risk assessment can be divided into two major categories: assessment of familial or genetic risk and assessment of environmental factors that may be causally related to cancer. Evaluation of familial risk should include both maternal and paternal lineages, with specific attention to cancers that co-exist in known hereditary cancer syndromes. Evaluation of environmental factors should focus on assessment of known modifiable factors, such as smoking, obesity, diet and physical activity.

Family History Assessment

Family history is a known risk factor for a multitude of chronic diseases, including cardiovascular disease, diabetes and cancer; thus, obtaining a family history of medical illness is a recognized and important component of primary care assessment. From the standpoint of cancer risk assessment, a thorough family history should include all of the following components:

  • Ethnic background of each grandparent
  • Information about both maternal and paternal relatives
  • Information on at least first- (parents, siblings, children), and second-degree (aunts, uncles, nieces, nephews, grandparents) relatives
  • Type of cancer, age at diagnosis and age at death for each family member with cancer, current age of family members living with cancer
  • Environmental exposures (including smoking, radiation, occupational exposures, etc).

Family history information should be briefly updated at each visit. The literature suggests that family history taking in community family practice is sub-optimal. In one study of primary care physicians, family history was discussed during only 51% of new patient visits and 22% of established patient visits (2). Physician factors associated with a greater likelihood of obtaining family history information included fewer years in practice and female gender. Family history was more likely to be discussed at well care visits. Patients 65 years or older were least likely to be asked about family history. A number of substantive barriers to obtaining a thorough family history in the primary care setting have been described, including lack of direct reimbursement (3) and perceived lack of genetic knowledge (4, 5).

The US Surgeon General, in conjunction with the Centers for Disease Control and the Department of Health and Human Services, has recently launched a national public health campaign called the US Surgeon General’s Family History Initiative. The goal of this effort is to increase awareness among both the general population and health care providers of the importance of knowing and understanding an individual’s family history. This initiative has led to the creation of videos aimed at patients that explain the importance of family history in primary medical care, and has also produced a tool for family history taking called “My Family Health Portrait” which is available in both a paper and a web-based format. This tool can be accessed on the internet at, and is designed to be completed by patients in conjunction with a primary care medical visit.

Knowledge of family history is important in practice because it can identify individuals with an increased disease susceptibility who may benefit from additional screening and possibly prevention interventions. The American Cancer Society recommends earlier and/or more intensive cancer screening for individuals with a family history of breast, colorectal and prostate cancer (see Table 1). While taking a cancer family history, it is important to pay special attention to cancers that occur as part of specific hereditary cancer syndromes.

Table 1
Screening Recommendations for Individuals with a Family History of Selected Cancers

Individuals with histories suggesting a hereditary syndrome may be considered for genetic evaluation and counseling by a specialty-trained provider such as a medical geneticist or genetic counselor. These individuals have received specialized training in the unique issues associated with genetic evaluation and testing. They provide education and pre- and post-test counseling, which are extremely important in helping patients understand the complex issues that they face when considering a genetic test for cancer predisposition.

A brief description of specific inherited syndromes associated with some of the more common and preventable cancers, including the involved genes, mode of inheritance, associated cancers, and screening and prevention options is presented below and summarized in Table 2. A more comprehensive listing of known inherited cancer syndromes can be found in the published clinical catalog of recognizable family cancer syndromes, “Concise Handbook of Familial Cancer Susceptibility Syndromes” (12).

Table 2
Selected Familial Cancer Syndromes, Responsible Genes and Clinical Manifestations (12)

Hereditary Breast and Ovarian Cancer

It is estimated that 5 – 10% of breast cancers occur in women with an inherited susceptibility to cancer (13). The majority of these are women with Hereditary Breast Ovarian Cancer Syndrome (HBOC), which is explained by deleterious mutations in the BRCA1 and BRCA/2 genes, although a number of less common genetic disorders, such as Li-Fraumeni Syndrome, Cowden Syndrome and Peutz-Jeghers also include a predisposition to breast cancer (12). These syndromes exhibit autosomal dominant inheritance. Personal and family history features suggestive of HBOC include the following:

  • Early onset breast cancer (age <40 or age <50 if Ashkenazi Jewish heritage
  • Ovarian cancer occurring in a women with a family history of breast or ovarian cancer
  • Breast and ovarian cancer occurring in the same woman
  • Bilateral breast cancer
  • Male breast cancer
  • Ashkenazi Jewish heritage and family history of breast cancer

Women with BRCA1 mutations have a 50-80% lifetime risk of breast cancer and a 20-40% lifetime risk of ovarian cancer. Women with BRCA2 mutations have a similar lifetime risk of breast cancer and a 10-20% lifetime risk of ovarian cancer. These women also have a 40-60% lifetime risk of contralateral breast cancer and an increased risk of cancer of the fallopian tube (14). Men in BRCA2 families have an estimated 15-25% lifetime risk of prostate cancer (15) and an estimated 6% lifetime risk of male breast cancer. In addition, members of BRCA1/2 families are thought to have an increased risk of pancreatic cancer. The identification of individuals with HBOC has implications for both cancer screening and the application of risk-reducing interventions. Published guidelines recommend that women with known or suspected BRCA mutations begin annual mammographic screening at age 25 or ten years prior to the age at diagnosis of the youngest breast cancer case in the family, whichever is sooner (6). In addition, based on data from nonrandomized screening trials and observational studies, the American Cancer Society (ACS) and the National Comprehensive Cancer Network (NCCN) recommend annual screening MRI for women with a strong family history of breast cancer or a known genetic predisposition (6, 16). MRI screening should also be considered in certain other high risk populations (see Table 3). Screening for ovarian cancer with yearly CA-125 and transvaginal ultrasound, beginning at age 35, is also generally recommended for BRCA mutation carriers, despite there being no proof that this strategy has clinical benefit (17). There are little data on screening recommendations for men with BRCA mutations. NCCN guidelines suggest twice yearly clinical breast examination and teaching of breast self-examination. In addition, a baseline mammogram should be considered, and annual mammograms may be reasonable if gynecomastia or glandular density are seen on the baseline exam.

Table 3
Recommendations for annual breast MRI screening (16)

Due to a markedly increased lifetime risk of breast and ovarian cancer, women with HBOC are generally counseled about the option of prophylactic surgery for risk reduction. Bilateral prophylactic mastectomy has been shown in multiple studies to reduce the risk of breast cancer by about 90% (18-20). Prophylactic oophorectomy dramatically reduces the risk of ovarian cancer in this high-risk population, but there remains a residual risk of primary peritoneal cancer (21, 22), an intra-abdominal neoplasm that is clinically and histologically indistinguishable from ovarian cancer. Oophorectomy has also been shown to reduce the risk of breast cancer by about 50% (21, 22), although the effect varies by age at surgery (23). In addition, the NCCN recommends that salpingectomy (removal of the fallopian tubes) be performed at the time of surgery, and advocates peritoneal washings and careful pathologic assessment with multiple fine sections of the ovaries and fallopian tubes. Chemopreventive options, such as tamoxifen and raloxifene, which have been shown to decrease the risk of breast cancer by about 50% in women at increased risk of breast cancer based on the Gail Model (see discussion below), have not been well studied in the genetically at-risk population (24-26).

Hereditary Colon Cancer

Approximately 20% of individuals diagnosed with colon cancer have a strong family history (two or more first- or second- degree relatives), and about 3-5% of colon cancers occur in the context of genetically defined high-risk syndromes (27). The two most common of these are Hereditary Non-Polyposis Colorectal Cancer (HNPCC or Lynch Syndrome) and Familial Adenomatous Polyposis (FAP). Both are inherited in an autosomal dominant fashion.

HNPCC-associated cancers result from mutations in one of several genes that participate in DNA mismatch repair, most notably MLH1 and MSH2, which account for approximately 80% of disease, MSH6, which is mutated in about 10-15% of cases, and rarely, PMS2. The molecular hallmark of colon cancer in individuals with HNPCC is microsatellite instability, which is the result of frequent insertion and deletion mutations in microsatellite repeats caused by defects in DNA mismatch repair (28), and is detectable in tumor tissue. HNPCC-related colon cancer is characterized by an early age at onset (mean age at diagnosis is 45 years compared with 63 years in the general population) and right-sided colonic predominance. Affected individuals have an estimated 80% lifetime risk of colon cancer (29). In addition, there is a substantial risk of both synchronous and metachronous colon cancer, and excess risks in affected family members of endometrial, ovarian, gastric, small intestine, brain and sebaceous skin cancers (30).

As with HBOC, the identification of individuals with HNPCC has important screening implications. NCCN guidelines recommend that these individuals begin annual or biennial screening colonoscopy at age 20-25 years, or 10 years prior to the age at diagnosis of youngest family member (whichever comes first). Total abdominal colectomy should be considered if high grade dysplasia is identified, or if adenomas that are not amenable to endoscopic resection are found. In addition, due to increased risks of ovarian and endometrial cancers and cancers of the urinary collecting system, consideration should be given to urinalysis with urine cytology, and to transvaginal ultrasound and CA-125 screening in women. Prophylactic hysterectomy and salpingo-oophorectomy may also be considered(31).

FAP is caused by mutations in the APC gene. This autosomal dominant syndrome is characterized by the presence of hundreds to thousands of adenomatous polyps beginning in the preteen years, which almost invariably undergo malignant degeneration by the age of 40 to 50 years. Since the lifetime penetrance of FAP related colon cancer approaches 100%, prophylactic subtotal colectomy followed by annual rectal endoscopy is recommended for affected individuals, but can be delayed until the polyp burden becomes too high to be safely managed colonoscopically (30).

Familial Prostate Cancer

Familial clustering of prostate cancer has been well described, but to date no specific high penetrance susceptibility genes have been identified, and thus clinical genetic testing is not currently available. A number of candidate genetic loci have been identified in linkage analyses and, more recently, in genome-wide association studies (32). However, the preponderance of data suggests that the genetic basis of prostate cancer is incredibly complex, and this is an area of active research.

Family history is among the strongest risk factors for prostate cancer; risk increases with earlier age at onset among relatives and with the number of affected family members. Estimated relative risks of prostate cancer ranges from about a two-fold increase in risk with one affected relative to a five-fold increase for individuals with two or more affected first-degree relatives (33). An increased risk of prostate cancer is also associated with other known cancer predisposition syndromes, most notably BRCA2 (34).

Potential screening modalities for prostate cancer include digital rectal examination (DRE) and prostate-specific antigen (PSA) testing, although the utility of these interventions is not well established. The current data are insufficient to determine whether screening for prostate cancer with DRE and PSA lead to a reduction in prostate cancer mortality (10). The American Cancer Society recommends that physicians should offer DRE and PSA screening to all men with a life expectancy of at least 10 years, beginning at age of 50, and to African American men or those with a family history of prostate cancer beginning at age 45. For men with multiple family members with an early age at onset of prostate cancer, it may be reasonable to perform a baseline PSA at age 40. Depending on the result of this initial test, additional testing may not be needed until age 45.

A number of randomized studies, including the highly publicized Prostate Cancer Prevention Trial, have shown that the use of 5-alpha-reductase inhibitors such as finasteride decreases the incidence of prostate cancer in men undergoing prostate cancer screening (35). Although none of these trials looked specifically at men with a family history of prostate cancer, similar reductions in risk were seen in men with and without a family history.

Familial Melanoma

It is estimated that 5-7% of melanoma patients are from genetically at-risk families. Familial melanoma is generally defined by the presence of three or more affected blood relatives in families located in regions of intense sun exposure, or two or more affected family members in areas with less intense sun exposure. Individuals with an inherited predisposition to melanoma are prone to early-onset disease (mean age at diagnosis is 34 years) and tend to develop multiple primary melanomas (36). Mutations in two melanoma susceptibility genes, CDKN2A and CDK4 are thought to be responsible for a large proportion of familial cases; however in greater than 50% of multiple-case families, no mutations in these genes are found, and the clinical utility of genetic testing for CDKN2A mutations is widely debated (6). Families with CDKN2A mutations have an average melanoma penetrance of 30% by age 50 and 67% by age 80 (37). Carriers of CDKN2A mutations also have a greatly increased risk of pancreatic cancer, with a cumulative lifetime risk approaching 17% (38), and a possible increased risk of breast cancer (39). The Melanoma Genetics Consortium recommends careful surveillance, including yearly or biannual clinical skin examinations, and patient and family education for individuals in whom familial melanoma is suspected (11).

Cancer Risk Assessment Models

Statistical models for cancer risk prediction fall into two broad categories: those that are used to predict the probability of being diagnosed with a particular cancer, and those that predict the likelihood of carrying a gene mutation that predisposes to a particular cancer or set of cancers. A number of commonly used risk assessment models for common cancers are described below.

Breast Cancer

The Gail model provides estimates of a woman’s 5-year and lifetime risk of breast cancer based on age, reproductive risk factors, family history and history of previous breast biopsy (40, 41). This model is simple to use and easily accessible on the internet ( The Gail model has been used to determine eligibility for breast cancer prevention trials in the United States. While this model performs very well on a population level, the accuracy of the model for predicting individual risk has been questioned (42). In addition, the Gail model may underestimate risk in women with a family history of breast cancer, since it only considers first-degree relatives (mothers, sisters, or daughters), and does not include age at diagnosis of relatives. It also does not consider paternal family history or family history of ovarian cancer, which may be of crucial importance in women with HBOC. The Gail Model is most appropriate for use among women over the age of 35 undergoing routine mammographic screening, and in this population can be very helpful in illustrating to a woman how her risk of breast cancer compares to other women of similar age.

The Claus model is useful for assessing breast cancer risk in women with a family history of breast cancer (43, 44). This model presents a series of tables with risk estimates based on family history of breast and ovarian cancer, and takes into account second-degree relatives (aunts), and age at diagnosis of family members. This model also considers both maternal and paternal family history. The Claus model is most useful for assessing breast cancer risk among women with a strong family history. In the setting of a strong family history, there are also several models that are currently used to estimate the risk of having a BRCA1/2 mutation. These include the BRCAPRO, BOADICEA and IBIS models (45). The latter two models incorporate both family history and other risk factors, and produce both mutation probabilities and breast and ovarian cancer risk estimates.

If the family history is strongly suggestive of an inherited susceptibility to breast cancer, referral to a cancer genetics professional should be considered. Referral in this setting will allow for a complete evaluation regarding likelihood of an inherited cancer susceptibility syndrome, pre-test genetic counseling, and genetic testing if appropriate. Cancer genetics professionals can aid in the development of a thorough cancer risk management plan, including screening, chemoprevention, and consideration of other risk-reducing options.

Colon Cancer

A number of models exist for assessing genetic risk of colon cancer. The Amsterdam Criteria (46, 47) were established to guide researchers and clinicians in identifying individuals who were likely to have HNPCC. These criteria are based on individual and family history of colon cancer or other HNPCC-related cancers, and take into account the number and relationship of affected family members and the age at diagnosis of affected individuals. The multiplicity of genes implicated in the etiology of HNPCC leads to complexity in confirming the diagnosis, as it is not practical to perform germline mutation testing on all HNPCC-related genes. The Bethesda Guidelines (48) were developed to guide the testing of tumors for microsatellite instability (MSI), and thereby improve identification of individuals with HNPCC. These Guidelines include age at diagnosis, presence of multiple tumors, and number and age at onset of relatives with HNPCC related tumors. Individuals with an appropriate family history and MSI-high tumors comprise a subgroup of subjects upon which germline mutation testing can be targeted. In addition, tumors can be evaluated for expression of the protein products of genes involved in mismatch repair (MMR) by immunohistochemistry. Absence of protein expression related to one of the MMR genes further aids in deciding which gene to test first.

Recently, simpler, more accessible tools have become available to predict the probability of HNPCC in individuals and families. The PREMM1,2 model, takes into account personal and family history of colon cancer, age at diagnosis, and presence of adenomas, endometrial cancer, or other HNPCC-related cancers in the proband and family members (49). This model calculates the probability of carrying a mutation in MLH1 or MSH2, the two genes most commonly associated with HNPCC, and is available on the internet at The MMRpro model is a slightly more complex web-based tool (available at ( In addition to the parameters described above, this latter model incorporates information about microsatellite instability testing and genetic testing (if performed), and estimates both the risk of carrying a deleterious mutation and the probability of developing colorectal or endometrial cancer over a specified period of time (50).

Researchers and statisticians at the NCI have also recently developed a colon cancer risk assessment tool (51). Also available online (, this tool incorporates screening history, family history, and a number of known lifestyle risk factors for colon cancer (such as diet, physical activity and use of non-steroidal anti-inflammatory drugs). It estimates 5-year, 10-year and lifetime risk of colon cancer for non-Hispanic white men and women aged 50 - 85.


It is estimated that more than 62,000 cases of melanoma will be diagnosed in 2008 (1). Melanomas evolve in a step-wise fashion, and survival is strongly influenced by depth of tumor invasion and lymph node status. Melanoma is an ideal example of a disease for which early detection is feasible and effective: it is increasingly common; can be identified non-invasively by visual inspection; and can be definitively diagnosed and cured in its early stages. Investigators at the National Cancer Institute have developed a melanoma risk prediction model that is easily administered by primary care physicians (52). The model incorporates information on patient age and gender, skin tone, tanning history, current geographical location, and skin examination, and produces an estimated 5-year absolute risk of melanoma. This model can be accessed on the internet at

Modifiable Cancer Risk Factors

It is believed that cancer may be a fundamentally preventable disease; as many as 90-95% of all cancers are attributed to potentially modifiable behavioral and environmental risk factors (53). Chief among these factors are tobacco, alcohol consumption and obesity. Thus, by assessing and influencing lifestyle factors during primary care visits, the physician may have a considerable effect on cancer incidence and patient outcomes.


Tobacco smoking accounts for one in five deaths each year (54) and one-third of all cancer deaths (53), and is the leading preventable cause of death in the United States. Smoking is associated with at least 14 different types of cancers including cancers of the lung, esophagus, larynx, oral cavity, pancreas, urinary bladder, kidney, stomach, uterine cervix, nasal cavity and nasal sinuses (55). The risk of these cancers increases with the dose and duration of smoking, but also decreases significantly after quitting (55, 56). Despite the known harmful effect of tobacco, more than 20% of American adults continue to use it; most of them smoke cigarettes (57). The same is true for adolescents; 25.7% of high school students reported using some kind of tobacco and 20% reported smoking cigarettes (58). A recent CDC report found that while most smokers (70%) are interested in quitting, and about 40% have attempted to quit, less than 5% succeeded (59). Primary care physicians are well positioned to assist patients’ attempts to quit smoking. In a recently published meta-analysis, physicians’ quitting advice to smokers, even when brief, significantly increased their probability of success (60).

Despite these compelling data, evidence suggests that physicians are not taking full advantage of this unique opportunity. Data from the National Ambulatory Medical Care survey showed that 32% of medical records contained no information regarding tobacco use, 81% of smokers had not received quitting assistance, and less than 2% had received a pharmacological treatment (61). In a recently-published clinical practice guideline that was designed to help physicians intervene most effectively (62), emphasis was placed on the importance of collecting smoking information from every patient, advising all smokers to quit, and providing different cessation strategies based on patients’ willingness to stop smoking. Physicians’ effort should also be directed toward former smokers in order to support their efforts at remaining tobacco free, and to follow them more closely, as they are still at higher risk of developing cancers compared with those who never smoked. In addition, targeting adolescents is crucial, both for helping young non-smokers avoid initiating tobacco use, as well as supporting those who attempt to stop. Adolescence appears to be a particularly vulnerable developmental stage related to initiating smoking behavior.


Alcohol intake is causally linked to cancers of the esophagus, oral cavity, pharynx and larynx (63), in which 25-68% of the cases are etiologically-related to alcohol (64). Cancer risk at these sites increases with the amount of alcohol consumed, and shows a multiplicative effect with smoking. For example, in the absence of smoking, heavy drinkers (those who consume 60 or more drinks/week) have double the risk of developing oropharyngeal cancers and are eight times more likely to develop esophageal cancers when compared with light or non-drinkers. Heavy smokers (those who smoked ≥25 cigarettes per day for ≥40 years) and heavy drinkers are 80 times more likely to develop oropharyngeal cancers, 12 times more likely to develop laryngeal cancers and 18 times more likely to develop esophageal cancers when compared with light or non-drinkers who don’t smoke (65). In addition, alcohol is a well-established risk factor for cancers of the liver (66), colorectum (67) and breast (68).

The epidemiological evidence suggesting a beneficial effect of alcohol consumption for coronary heart diseases (CHD) (69) does complicate formulating a rational alcohol consumption recommendation. However, the weak protective effect for CHD observed only in current drinkers (5-20%), and the attenuation of risk reduction observed in those living outside the Mediterranean region (69) might reflect a confounded association, in which a third factor (such as diet) that is associated with drinking is the cause of the observed protective effect. Additionally, the increased CHD mortality observed in middle-aged men might reflect a survival bias. Given the risk-benefit profile of alcohol, it is important to assess the patients’ history of alcohol use, and its intensity. It is also important to assess factors that modulate cancer risk when combined with alcohol such as smoking for upper digestive and respiratory tract cancers, and hepatitis C or B infection for liver cancer.


Obesity is a major heath problem and an established cancer risk factor. It accounts for 14-20% of cancer mortality in the U.S. (70). Body mass index (BMI) is the most commonly used measure of healthy weight, in which both weight and height are taken into account. A BMI of 18.5 to 24.9 kg/m2 is considered “normal”; 25-29.9 kg/m2 is considered “overweight,” and greater than 30 kg/m2 is considered “obese.” According to the most recent National Health and Nutrition Examination Survey (NHANES 2005-2006), more than 30% of American adults are obese (71). Other weight indices include waist circumference and waist-to-hip ratio, which both reflect body fat distribution (72). There is strong evidence that obesity is associated with increased risk of the following cancers: esophagus, colorectum, liver, gall bladder, pancreas, kidney, non-Hodgkin’s lymphoma, multiple myeloma, stomach, prostate, breast, cervix and ovary (70). Furthermore, some studies have suggested a protective role for intentional weight loss on overall cancer risk and on cancers of the breast, colon and endometrium (73). Several health organizations emphasize the role of the primary care physicians in identifying and treating obesity (74, 75). However, physicians may lack the training required to effectively provide adequate nutritional education; many have expressed an interest in learning more in the area of weight management (76, 77).

The National Heart, Lung and Blood Institute published a clinical guideline to help physicians identify, evaluate and treat obesity (78). According to this guideline, people with BMI of ≥25 kg/m2 or a high waist circumference (> 88 cm for females and > 102 cm for males), who have at least two obesity-related risk factors, such as diabetes and cardiovascular disease, are candidates for treatment. The guideline recommends an initial goal of 10% loss of baseline weight, at a target rate of 0.45 to 0.90 kg/week, followed by re-evaluation. The guideline also reviews several alternative therapeutic strategies, including dietary modification, increase in physical activity, behavioral therapy, pharmacotherapy and surgery. It is important to remember that obesity is a chronic disease and requires ongoing monitoring with the goal of maintaining healthy weight throughout life.

Diet and Physical Activity

The role of diet and physical activity in modulating cancer risk beyond their effect on weight control is increasingly being recognized. The findings that certain nutrients may protect against specific cancers (79) and that physical activity may regulate sex hormones and alter immune function lend support to the hypothesis that these factors exert independent effects on cancer risk.

A healthy diet may prevent a considerable number of cancer cases. A diet that includes fresh fruits and vegetables is thought to reduce the risk of most epithelial cancers (80). A detailed evidence-based scientific review regarding dietary component and cancer, by cancer site, was recently published by the World Cancer Research Fund/American Institute for Cancer Research (79). In summary, it concluded that there is sufficient evidence of increased risk of liver cancer in people exposed to a diet contaminated with aflatoxin (a naturally occurring toxic metabolite produced by certain fungi (Aspergillus flavis), and found on food products such as corn and peanuts, peanut butter), and lung cancer for those drinking arsenic contaminated water, to warrant active efforts to reduce/avoid these exposures. Conversely, garlic and dietary fiber are suggested to protect against colorectal cancer; lycopene against prostate cancer; and B-carotene and Vitamin C against esophageal cancer.

There is accumulating evidence that physical activity is associated with decreased risks of breast and colon cancer (81). A protective association between physical activity and other hormone-related cancers, such as prostate and endometrial, is also plausible but the evidence for these associations is less robust (81, 82). There is also solid evidence that physical activity affects the risk of other chronic diseases such as diabetes and heart disease. The American Cancer Society expert-based recommendations suggest that engaging in moderate to vigorous physical activity for 30-60 minutes on at least 5 days/week will reduce an individual’s cancer risk (83). Similar to the data on smoking cessation, a physician recommendation for increased physical activity has been shown to be an effective tool for motivating behavioral change (84, 85). However, physicians tend to target people who have chronic diseases, or who are overweight or obese for physical activity advice (86), rather than providing these recommendations more widely.

Summary and Conclusions

Primary care physicians are uniquely situated to identify individuals at increased genetic or environmental risk of cancer. The early identification of a suspected heritable cancer syndrome can lead to additional evaluation and to interventions that can substantially decrease cancer risk. Web-based tools for collecting and summarizing family history information and for predicting individual risks of certain cancers and familial syndromes are easily accessible, and are available for use by the primary care physician. Individuals with a high likelihood of having an inherited syndrome should be seriously considered for referral to a cancer genetics professional for further work-up and treatment, including genetic testing and risk reduction strategies.

Special attention should also be paid to potentially modifiable cancer risk factors in the course of advising primary care patients regarding a healthy lifestyle. The fact that certain modifiable behaviors are associated with increased risk not only of cancers but also of other chronic disease creates an opportunity for early intervention. Clinical guidelines targeting modifiable cancer risk factors are available, and can facilitate applying these health care principles in the primary care setting.


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1. Jemal A, Siegel R, Ward E, Hao Y, Xu J, Murray T, et al. Cancer statistics, 2008. CA Cancer J Clin. 2008;58(2):71–96. [PubMed]
2. Acheson LS, Wiesner GL, Zyzanski SJ, Goodwin MA, Stange KC. Family history-taking in community family practice: implications for genetic screening. Genet Med. 2000;2(3):180–5. [PubMed]
3. Rich EC, Burke W, Heaton CJ, Haga S, Pinsky L, Short MP, et al. Reconsidering the family history in primary care. J Gen Intern Med. 2004;19(3):273–80. [PMC free article] [PubMed]
4. Fry A, Campbell H, Gudmunsdottir H, Rush R, Porteous M, Gorman D, et al. GPs’ views on their role in cancer genetics services and current practice. Fam Pract. 1999;16(5):468–74. [PubMed]
5. Watson EK, Shickle D, Qureshi N, Emery J, Austoker J. The ‘new genetics’ and primary care: GPs’ views on their role and their educational needs. Fam Pract. 1999;16(4):420–5. [PubMed]
6. Genetic/Familial High Risk Assessment: Breast and Ovarian. NCCN Clinical Practice Guidelines in Oncology: National Comprehensive Cancer Network. 2008
7. Breast Cancer Screening and Diagnosis Guidelines. NCCN Clinical Practice Guidelines in Oncology: National Comprehensive Cancer Network. 2008 [PubMed]
8. Colorectal Cancer Screening. NCCN Clinical Practice Guidelines in Oncology: National Comprehensive Cancer Network. 2008
9. American Cancer Society Guidelines for the Early Detection of Cancer [PubMed]
10. Harris R, Lohr KN. Screening for prostate cancer: an update of the evidence for the U.S. Preventive Services Task Force. Ann Intern Med. 2002;137(11):917–29. [PubMed]
11. Kefford RF, Newton Bishop JA, Bergman W, Tucker MA. Counseling and DNA testing for individuals perceived to be genetically predisposed to melanoma: A consensus statement of the Melanoma Genetics Consortium. J Clin Oncol. 1999;17(10):3245–51. [PubMed]
12. Lindor NM, McMaster ML, Lindor CJ, Greene MH. Concise handbook of familial cancer susceptibility syndromes - second edition. J Natl Cancer Inst Monogr. 2008;(38):1–93. [PubMed]
13. Familial breast cancer: collaborative reanalysis of individual data from 52 epidemiological studies including 58,209 women with breast cancer and 101,986 women without the disease. Lancet. 2001;358(9291):1389–99. [PubMed]
14. Zweemer RP, van Diest PJ, Verheijen RH, Ryan A, Gille JJ, Sijmons RH, et al. Molecular evidence linking primary cancer of the fallopian tube to BRCA1 germline mutations. Gynecol Oncol. 2000;76(1):45–50. [PubMed]
15. Cancer risks in BRCA2 mutation carriers. The Breast Cancer Linkage Consortium. J Natl Cancer Inst. 1999;91(15):1310–6. [PubMed]
16. Saslow D, Boetes C, Burke W, Harms S, Leach MO, Lehman CD, et al. American Cancer Society guidelines for breast screening with MRI as an adjunct to mammography. CA Cancer J Clin. 2007;57(2):75–89. [PubMed]
17. NIH consensus conference. Ovarian cancer. Screening, treatment, and follow-up. NIH Consensus Development Panel on Ovarian Cancer. Jama. 1995;273(6):491–7. [PubMed]
18. Hartmann LC, Sellers TA, Schaid DJ, Frank TS, Soderberg CL, Sitta DL, et al. Efficacy of bilateral prophylactic mastectomy in BRCA1 and BRCA2 gene mutation carriers. J Natl Cancer Inst. 2001;93(21):1633–7. [PubMed]
19. Rebbeck TR, Friebel T, Lynch HT, Neuhausen SL, van ’t Veer L, Garber JE, et al. Bilateral prophylactic mastectomy reduces breast cancer risk in BRCA1 and BRCA2 mutation carriers: the PROSE Study Group. J Clin Oncol. 2004;22(6):1055–62. [PubMed]
20. Scheuer L, Kauff N, Robson M, Kelly B, Barakat R, Satagopan J, et al. Outcome of preventive surgery and screening for breast and ovarian cancer in BRCA mutation carriers. J Clin Oncol. 2002;20(5):1260–8. [PubMed]
21. Kauff ND, Satagopan JM, Robson ME, Scheuer L, Hensley M, Hudis CA, et al. Risk-reducing salpingo-oophorectomy in women with a BRCA1 or BRCA2 mutation. N Engl J Med. 2002;346(21):1609–15. [PubMed]
22. Rebbeck TR, Lynch HT, Neuhausen SL, Narod SA, Van’t Veer L, Garber JE, et al. Prophylactic oophorectomy in carriers of BRCA1 or BRCA2 mutations. N Engl J Med. 2002;346(21):1616–22. [PubMed]
23. Kramer JL, Velazquez IA, Chen BE, Rosenberg PS, Struewing JP, Greene MH. Prophylactic oophorectomy reduces breast cancer penetrance during prospective, long-term follow-up of BRCA1 mutation carriers. J Clin Oncol. 2005;23(34):8629–35. [PubMed]
24. Fisher B, Costantino JP, Wickerham DL, Redmond CK, Kavanah M, Cronin WM, et al. Tamoxifen for prevention of breast cancer: report of the National Surgical Adjuvant Breast and Bowel Project P-1 Study. J Natl Cancer Inst. 1998;90(18):1371–88. [PubMed]
25. King MC, Wieand S, Hale K, Lee M, Walsh T, Owens K, et al. Tamoxifen and breast cancer incidence among women with inherited mutations in BRCA1 and BRCA2: National Surgical Adjuvant Breast and Bowel Project (NSABP-P1) Breast Cancer Prevention Trial. Jama. 2001;286(18):2251–6. [PubMed]
26. Vogel VG, Costantino JP, Wickerham DL, Cronin WM, Cecchini RS, Atkins JN, et al. Effects of tamoxifen vs raloxifene on the risk of developing invasive breast cancer and other disease outcomes: the NSABP Study of Tamoxifen and Raloxifene (STAR) P-2 trial. Jama. 2006;295(23):2727–41. [PubMed]
27. Grady WM. Genetic testing for high-risk colon cancer patients. Gastroenterology. 2003;124(6):1574–94. [PubMed]
28. Boland CR, Thibodeau SN, Hamilton SR, Sidransky D, Eshleman JR, Burt RW, et al. A National Cancer Institute Workshop on Microsatellite Instability for cancer detection and familial predisposition: development of international criteria for the determination of microsatellite instability in colorectal cancer. Cancer Res. 1998;58(22):5248–57. [PubMed]
29. Aarnio M, Sankila R, Pukkala E, Salovaara R, Aaltonen LA, de la Chapelle A, et al. Cancer risk in mutation carriers of DNA-mismatch-repair genes. Int J Cancer. 1999;81(2):214–8. [PubMed]
30. Lynch HT, de la Chapelle A. Hereditary colorectal cancer. N Engl J Med. 2003;348(10):919–32. [PubMed]
31. Lynch HT, Lynch JF, Lynch PM, Attard T. Hereditary colorectal cancer syndromes: molecular genetics, genetic counseling, diagnosis and management. Fam Cancer. 2008;7(1):27–39. [PubMed]
32. Ostrander EA, Johannesson B. Prostate cancer susceptibility loci: finding the genes. Adv Exp Med Biol. 2008;617:179–90. [PMC free article] [PubMed]
33. Zeegers MP, Jellema A, Ostrer H. Empiric risk of prostate carcinoma for relatives of patients with prostate carcinoma: a meta-analysis. Cancer. 2003;97(8):1894–903. [PubMed]
34. Ostrander EA, Udler MS. The role of the BRCA2 gene in susceptibility to prostate cancer revisited. Cancer Epidemiol Biomarkers Prev. 2008;17(8):1843–8. [PMC free article] [PubMed]
35. Wilt TJ, MacDonald R, Hagerty K, Schellhammer P, Kramer BS. Five-alpha-reductase Inhibitors for prostate cancer prevention. Cochrane Database Syst Rev. 2008;(2):CD007091. [PubMed]
36. Goldstein AM, Chan M, Harland M, Gillanders EM, Hayward NK, Avril MF, et al. High-risk melanoma susceptibility genes and pancreatic cancer, neural system tumors, and uveal melanoma across GenoMEL. Cancer Res. 2006;66(20):9818–28. [PubMed]
37. Bishop DT, Demenais F, Goldstein AM, Bergman W, Bishop JN, Bressac-de Paillerets B, et al. Geographical variation in the penetrance of CDKN2A mutations for melanoma. J Natl Cancer Inst. 2002;94(12):894–903. [PubMed]
38. Pho L, Grossman D, Leachman SA. Melanoma genetics: a review of genetic factors and clinical phenotypes in familial melanoma. Curr Opin Oncol. 2006;18(2):173–9. [PubMed]
39. Borg A, Sandberg T, Nilsson K, Johannsson O, Klinker M, Masback A, et al. High frequency of multiple melanomas and breast and pancreas carcinomas in CDKN2A mutation-positive melanoma families. J Natl Cancer Inst. 2000;92(15):1260–6. [PubMed]
40. Costantino JP, Gail MH, Pee D, Anderson S, Redmond CK, Benichou J, et al. Validation studies for models projecting the risk of invasive and total breast cancer incidence. J Natl Cancer Inst. 1999;91(18):1541–8. [PubMed]
41. Gail MH, Brinton LA, Byar DP, Corle DK, Green SB, Schairer C, et al. Projecting individualized probabilities of developing breast cancer for white females who are being examined annually. J Natl Cancer Inst. 1989;81(24):1879–86. [PubMed]
42. Rockhill B, Spiegelman D, Byrne C, Hunter DJ, Colditz GA, et al. Validation of the Gail et al. model of breast cancer risk prediction and implications for chemoprevention. J Natl Cancer Inst. 2001;93(5):358–66. [PubMed]
43. Claus EB, Risch N, Thompson WD. The calculation of breast cancer risk for women with a first degree family history of ovarian cancer. Breast Cancer Res Treat. 1993;28(2):115–20. [PubMed]
44. Claus EB, Risch N, Thompson WD. Autosomal dominant inheritance of early-onset breast cancer. Implications for risk prediction. Cancer. 1994;73(3):643–51. [PubMed]
45. Antoniou AC, Hardy R, Walker L, Evans DG, Shenton A, Eeles R, et al. Predicting the likelihood of carrying a BRCA1 or BRCA2 mutation: validation of BOADICEA, BRCAPRO, IBIS, Myriad and the Manchester scoring system using data from UK genetics clinics. J Med Genet. 2008;45(7):425–31. [PubMed]
46. Vasen HF, Mecklin JP, Khan PM, Lynch HT. The International Collaborative Group on Hereditary Non-Polyposis Colorectal Cancer (ICG-HNPCC) Dis Colon Rectum. 1991;34(5):424–5. [PubMed]
47. Vasen HF, Watson P, Mecklin JP, Lynch HT. New clinical criteria for hereditary nonpolyposis colorectal cancer (HNPCC, Lynch syndrome) proposed by the International Collaborative group on HNPCC. Gastroenterology. 1999;116(6):1453–6. [PubMed]
48. Laghi L, Bianchi P, Roncalli M, Malesci A. Re: Revised Bethesda guidelines for hereditary nonpolyposis colorectal cancer (Lynch syndrome) and microsatellite instability. J Natl Cancer Inst. 2004;96(18):1402–3. author reply 1403-4. [PubMed]
49. Balmana J, Stockwell DH, Steyerberg EW, Stoffel EM, Deffenbaugh AM, Reid JE, et al. Prediction of MLH1 and MSH2 mutations in Lynch syndrome. Jama. 2006;296(12):1469–78. [PubMed]
50. Chen S, Wang W, Lee S, Nafa K, Lee J, Romans K, et al. Prediction of germline mutations and cancer risk in the Lynch syndrome. Jama. 2006;296(12):1479–87. [PMC free article] [PubMed]
51. Freedman AN, Slattery ML, Ballard-Barbash R, Willis G, Cann BJ, Pee D, et al. Colorectal cancer risk prediction tool for white men and women without known susceptibility. Journal of Clinical Oncology. 2008 ePub ahead of print. [PMC free article] [PubMed]
52. Fears TR, Guerry Dt, Pfeiffer RM, Sagebiel RW, Elder DE, Halpern A, et al. Identifying individuals at high risk of melanoma: a practical predictor of absolute risk. J Clin Oncol. 2006;24(22):3590–6. [PubMed]
53. Anand P, Kunnumakkara AB, Sundaram C, Harikumar KB, Tharakan ST, Lai OS, et al. Cancer is a preventable disease that requires major lifestyle changes. Pharm Res. 2008;25(9):2097–116. [PMC free article] [PubMed]
54. The Health Consequences of Smoking: A Report of the Surgeon General: U.S.Department of Health and Human Services, Centers for Disease Control and Prevention, National Center for Chronic Disease Prevention and Health Promotion. 2004 2008/10/16.
55. IARC Monographs on the Evaluation of Carcinogenic Risks to Humans. Lyon: IARC press; 2004.
56. Peto R, Darby S, Deo H, Silcocks P, Whitley E, Doll R. Smoking, smoking cessation, and lung cancer in the UK since 1950: combination of national statistics with two case-control studies. Bmj. 2000;321(7257):323–9. [PMC free article] [PubMed]
57. Tobacco use among adults--United States, 2005. MMWR Morb Mortal Wkly Rep. 2006;55(42):1145–8. [PubMed]
58. Eaton DK, Kann L, Kinchen S, Shanklin S, Ross J, Hawkins J, et al. Youth risk behavior surveillance--United States, 2007. MMWR Surveill Summ. 2008;57(4):1–131. [PubMed]
59. Cigarette smoking among adults--United States, 2002. MMWR Morb Mortal Wkly Rep. 2004;53(20):427–31. [PubMed]
60. Stead LF, Bergson G, Lancaster T. Physician advice for smoking cessation. Cochrane Database Syst Rev. 2008;(2):CD000165. [PubMed]
61. Ferketich AK, Khan Y, Wewers ME. Are physicians asking about tobacco use and assisting with cessation? Results from the 2001-2004 national ambulatory medical care survey (NAMCS) Prev Med. 2006;43(6):472–6. [PubMed]
62. Fiore MC, Ja,n CR, Baker TB, et al. Clinical Practice Guideline: Treating Tobacco Use and Dependence: 2008 Update. Centers for Disease Control and Prevention, US Department of Health and Human Services
63. IARC monographs on the evaluation of carcinogenic risk to humans: alcohol drinking. Lyon: IARC; 1988. International agency for Research on C.
64. La Vecchia C, Tavani A, Franceschi S, Levi F, Corrao G, Negri E. Epidemiology and prevention of oral cancer. Oral Oncol. 1997;33(5):302–12. [PubMed]
65. Franceschi S, Talamini R, Barra S, Baron AE, Negri E, Bidoli E, et al. Smoking and drinking in relation to cancers of the oral cavity, pharynx, larynx, and esophagus in northern Italy. Cancer Res. 1990;50(20):6502–7. [PubMed]
66. Pelucchi C, Gallus S, Garavello W, Bosetti C, La Vecchia C. Alcohol and tobacco use, and cancer risk for upper aerodigestive tract and liver. Eur J Cancer Prev. 2008;17(4):340–4. [PubMed]
67. Bongaerts BW, van den Brandt PA, Goldbohm RA, de Goeij AF, Weijenberg MP. Alcohol consumption, type of alcoholic beverage and risk of colorectal cancer at specific subsites. Int J Cancer. 2008;123(10):2411–7. [PubMed]
68. Longnecker MP. Alcoholic beverage consumption in relation to risk of breast cancer: meta-analysis and review. Cancer Causes Control. 1994;5(1):73–82. [PubMed]
69. Corrao G, Rubbiati L, Bagnardi V, Zambon A, Poikolainen K. Alcohol and coronary heart disease: a meta-analysis. Addiction. 2000;95(10):1505–23. [PubMed]
70. Calle EE, Rodriguez C, Walker-Thurmond K, Thun MJ. Overweight, obesity, and mortality from cancer in a prospectively studied cohort of U.S. adults. N Engl J Med. 2003;348(17):1625–38. [PubMed]
71. Ogden CL, Carroll MD, McDowell MA, Flegal KM. Obesity among adults in the United States-no change since 2003-2004. Hayttsville, MD: National Center for Health Statistics; 2007. Report No.: NCHS data brief no.1.
72. Pischon T, Nothlings U, Boeing H. Obesity and cancer. Proc Nutr Soc. 2008;67(2):128–45. [PubMed]
73. Parker ED, Folsom AR. Intentional weight loss and incidence of obesity-related cancers: the Iowa Women’s Health Study. Int J Obes Relat Metab Disord. 2003;27(12):1447–52. [PubMed]
74. Executive summary of the clinical guidelines on the identification, evaluation, and treatment of overweight and obesity in adults. Arch Intern Med. 1998;158(17):1855–67. [PubMed]
75. Nawaz H, Katz DL. American College of Preventive Medicine Practice Policy statement. Weight management counseling of overweight adults. Am J Prev Med. 2001;21(1):73–8. [PubMed]
76. Mihalynuk TV, Knopp RH, Scott CS, Coombs JB. Physician informational needs in providing nutritional guidance to patients. Fam Med. 2004;36(10):722–6. [PubMed]
77. Mihalynuk TV, Scott CS, Coombs JB. Self-reported nutrition proficiency is positively correlated with the perceived quality of nutrition training of family physicians in Washington State. Am J Clin Nutr. 2003;77(5):1330–6. [PubMed]
78. Screening for obesity in adults: recommendations and rationale. Ann Intern Med. 2003;139(11):930–2. [PubMed]
79. Food, Nutrition, Physical activity, and the Prevention of Cancer: A Global Perspective. Washington, DC: AICR; 2007. World Cancer Research F, American institute for Cancer R. 2008/10/21/
80. La Vecchia C, Altieri A, Tavani A. Vegetables, fruit, antioxidants and cancer: a review of Italian studies. Eur J Nutr. 2001;40(6):261–7. [PubMed]
81. Friedenreich CM, Orenstein MR. Physical activity and cancer prevention: etiologic evidence and biological mechanisms. J Nutr. 2002;132(11 Suppl):3456S–3464S. [PubMed]
82. Vainio H, Kaaks R, Bianchini F. Weight control and physical activity in cancer prevention: international evaluation of the evidence. Eur J Cancer Prev. 2002;11(Suppl 2):S94–100. [PubMed]
83. Kushi LH, Byers T, Doyle C, Bandera EV, McCullough M, McTiernan A, et al. American Cancer Society Guidelines on Nutrition and Physical Activity for cancer prevention: reducing the risk of cancer with healthy food choices and physical activity. 2006;56(5):254–281. [PubMed]
84. Calfas KJ, Long BJ, Sallis JF, Wooten WJ, Pratt M, Patrick K. A controlled trial of physician counseling to promote the adoption of physical activity. Prev Med. 1996;25(3):225–33. [PubMed]
85. Lewis BS, Lynch WD. The effect of physician advice on exercise behavior. Prev Med. 1993;22(1):110–21. [PubMed]
86. Eakin E, Brown W, Schofield G, Mummery K, Reeves M. General practitioner advice on physical activity--who gets it? Am J Health Promot. 2007;21(4):225–8. [PubMed]