Key features of cancer cells (hallmarks):

• Continuous growth and division, ignoring the body’s signals to stop.

• Ability to evade programmed cell death (apoptosis).

• Development of their own blood supply (angiogenesis).

• Ability to invade surrounding tissues and spread to distant sites.

• Evasion of the immune system.

 

Why Does Cancer Develop?

 

Cancer cells develop when normal cells undergo abnormal changes.

These changes include the cells ignoring signals to stop growing, and because of this they develop the ability to invade nearby tissues, increasing the growth of blood vessels, hiding from the immune system, and drawing on extra nutrients to develop. These changes happen when there are errors or damage to the underlying genetic material (DNA) of cells. The source of these errors can be genetic (i.e., passed down from parents), environmental factors (for example, smoking, radiation, chemical exposures), a combination of both, or completely spontaneous¹. Over time, as cells accumulate more genetic changes, they may transform into cancer cells. Figure 1. Simplified Diagram of Cancer Development Table 1. Factors that Contribute to Cancer Development Category Genetic Examples BRCA1/2 mutations, TP53 mutations Environmental Smoking, asbestos, UV radiation Lifestyle Infectious Poor diet, obesity, alcohol, inactivity HPV, Hepatitis B/C, H. pylori Mechanism Altered DNA repair, loss of tumor suppression Direct DNA damage, inflammation Chronic inflammation, hormonal changes Viral DNA integration, chronic infection/inflammation How Do Cancer Cells Spread? One of the main features distinguishing cancer cells from normal cells is their ability and desire to invade other tissues¹,². The process of cancer spread is called metastasis. In this process, the cells break away from their origin and travel either through the blood or the lymphatic system to reach other organ systems in the body. Once there, they can form new tumors that may disrupt the function of the affected organ.

 

Different types of cancer preferentially travel to different organ systems.

For example:

• Lung cancer cells often spread to the bone and brain.

• Stomach cancer cells often spread to the liver and abdominal lining.

• Breast cancer cells may spread to the lungs, liver, bone, or brain.

• Prostate cancer often spreads to the bone.

*Remember that cancer cells can spread from any organ to any other organ Figure 2. Pathways of Cancer Spread PREVENTION SECTION Lifestyle & Occupational Factors There are several strategies to prevent the onset of cancer. The majority of these recommendations involve adopting a healthy lifestyle, which includes a balanced diet, regular exercise, and avoiding tobacco and alcohol³. Diet and Weight Management: Recommendations for diet include consuming a diet rich in vegetables, fruits, and beans while limiting “fast foods” and processed foods high in fat, starch, and sugars. The antioxidants and anti-inflammatory compounds in whole foods help protect cells. In addition to maintaining a healthy diet, a healthy weight is also essential as obesity itself can release inflammatory markers that then lead to the development of cancer cells. Obesity has also been linked to hormonal changes, such as increased estrogen and insulin levels, which may promote the growth of certain cancers (e.g., breast, endometrial, and colorectal cancers). Alcohol: Alcohol is another toxic substance that has now been established to develop cancer, especially breast, esophageal, liver, and colorectal cancer. While earlier studies found benefits of alcohol use in moderation, newer evidence has shown any amount of alcohol consumption increases the risk of cancer through increasing stress and inflammation in cells. This mechanism has been clearly identified in breast cancer, where alcohol was shown to promote cancer cell formation and metastasis. Exercise and Activity: Maintaining regular physical activity is another factor that reduces the risk of various cancers, including breast, colorectal, bladder, endometrial, esophageal, and stomach cancer. While the exact mechanism is unknown, we know exercise can inadvertently reduce inflammation, regulate hormone levels, and activate the immune system, thus decreasing the risk of cancer development. Even moderate activity such as walking 30 minutes a day has shown protective benefits. Sun Exposure and Vitamin D: Sun exposure and vitamin D consumption are two other factors to consider. It is important to reduce sun exposure to the skin and use protective creams to prevent the development of skin cancers. However, it is also essential to balance limiting sun exposure with vitamin D deficiency, which itself can contribute to the development of cancer. Therefore, a balanced recommendation is to protect one’s skin from UV rays and use sunscreen while also measuring vitamin D levels and supplementing as necessary. Smoking: While all of the above recommendations are excellent preventive strategies against cancer, arguably the most significant risk factor for cancer is smoking cigarettes. The relationship between smoking cigarettes and lung, head and neck, stomach, colorectal, bladder, kidney, liver, and cervical cancers has been strongly established. Additionally, the mechanism underlying the impact of smoking on cancer development has been identified as well, as smoking directly contributes to DNA damage within normal cells, causing changes that create cancer cells³. Importantly, second-hand smoke also increases risk for family members and co-workers.

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Occupational Exposures:

 

Finally, in addition to individual risk factors, occupational risk factors must also be considered. The main cancer-causing substances and exposures in the workplace include: • Solar radiation (leading to melanoma and other types of skin cancer)

• Asbestos (leading to lung cancer, mesothelioma, laryngeal cancer, and ovarian cancer)

• Diesel engine exhaust (leading to lung and bladder cancer)

• Crystalline silica (leading to lung cancer)

Thus, wearing appropriate PPE and ensuring workplace audits with regards to exposures, especially for occupations in which these exposures can routinely occur, is another preventable risk factor against cancer⁴. Table 2. Lifestyle and Occupational Risk Factors for Cancer Factor Tobacco use Alcohol Diet & obesity Physical inactivity UV exposure Occupational exposure Examples Cigarettes, cigars, second-hand smoke Beer, wine, spirits High-fat processed foods, low fruits/vegetables Sedentary lifestyle Outdoor work, tanning beds Asbestos, diesel exhaust, silica Cancers Linked Lung, bladder, kidney, stomach, cervical, head & neck Breast, colorectal, liver, esophagus Breast, colorectal, endometrial, pancreas Breast, colorectal, bladder, endometrial Melanoma, skin cancer Lung, bladder, mesothelioma, ovarian Prevention Strategy Smoking cessation programs, avoiding exposure Limit or avoid alcohol use Balanced diet, weight management Regular exercise (150 min/week) Sunscreen, protective clothing, limit peak sun PPE, workplace safety monitoring Vaccination & Treatment In addition to avoiding risk factors through lifestyle or occupational changes, there are vaccinations and treatments that prevent the development of cancer.  Hepatitis B Vaccine (HBV): The HBV vaccine is in fact the world’s first anti-cancer vaccine⁵. By preventing chronic hepatitis B infections, the vaccine prevents the development of hepatocellular carcinoma, a type of liver cancer. The vaccine is recommended for newborns in Iran and has significantly reduced the number of new cases of liver cancer. Some individuals are “non-responders” to the HBV vaccine and require additional boosts of the vaccine throughout their life to ensure they have built immunity against the virus. Therefore, it is essential to carefully monitor the levels of HBV immunity through your healthcare provider to ensure you are protected⁵. HPV Vaccine: The HPV vaccine prevents against common types of the HPV virus (mainly HPV 16 and 18)⁶. These viruses can cause cervical, head and neck, anal, penile, vaginal, and vulvar cancers. The vaccine builds the immune system to recognize these cancercausing strains of HPV and effectively protects against the afore-mentioned cancers. The vaccine is recommended from ages 9 to 45 and may be considered beyond that on an individual basis.

 

Infection Treatment:

 

In addition to vaccinations, ensuring appropriate treatment for certain infections can also reduce the risk of cancer. Two specific infections that are associated with cancer are:

• Helicobacter pylori (H. pylori): a bacterial infection that can cause stomach cancer. Treatment with antibiotics to eradicate the infection can significantly reduce the risk of developing stomach cancer. Patients with active ulcers should be tested and treated if positive⁷.

• Schistosoma haematobium: a parasitic infection that can lead to bladder cancer.

 

The chronic inflammation caused by this parasite increases cancer risk. Eradicating the parasite with antiparasitic medications helps prevent bladder cancer⁸. Cancer-Specific Risk Factors While the afore-mentioned lifestyle, occupational, and treatment-directed factors can be helpful in reducing the overall risk of cancer, there are specific factors associated with the development of various cancers which are summarized in the table below. Cancer Type Risk Factors Breast Colorectal Lung Prostate Bladder Endometrial Ovarian Cervical Stomach Melanoma Pancreatic Liver (Hepatocellular carcinoma) Esophageal Kidney (Renal Cell Carcinoma) Head & Neck (Oral, Oropharyngeal, Laryngeal) Thyroid Female sex, older age, family history, BRCA1/2 mutations, early menarche, late menopause, obesity, alcohol, hormone replacement therapy, nulliparity (ie no previous pregnancies), physical inactivity Older age, family history, Lynch syndrome, obesity, physical inactivity, high red/processed meat intake, smoking, alcohol, type 2 diabetes Smoking (primary and second-hand exposure), radon, occupational exposures (asbestos, silica), air pollution, family history, prior lung disease Older age, family history, BRCA2 mutations, obesity, diet high in animal fat Smoking, occupational exposures (aromatic amines), chronic bladder inflammation, age, male sex, family history Obesity, unopposed estrogen therapy, early menarche, late menopause, nulliparity, Lynch syndrome, diabetes, hypertension Family history, BRCA1/2 mutations, Lynch syndrome, nulliparity, endometriosis, older age Persistent HPV infection, early sexual activity, multiple sexual partners, smoking, immunosuppression, lack of screening Helicobacter pylori infection, smoking, high salt diet, family history, older age, male sex, certain hereditary syndromes UV exposure, fair skin, family history, CDKN2A mutations, numerous moles, history of sunburns Family history, BRCA2 and other hereditary syndromes, chronic pancreatitis, smoking, obesity, type 2 diabetes, older age Chronic hepatitis B or C infection, cirrhosis (any cause), aflatoxin exposure, alcohol use, obesity, diabetes, hemochromatosis Smoking, alcohol, gastroesophageal reflux disease (GERD), Barrett’s esophagus, obesity, achalasia, caustic injury Smoking, obesity, hypertension, family history, von HippelLindau syndrome Smoking, alcohol, HPV infection (especially HPV-16), poor oral hygiene, occupational exposures (wood dust, paint fumes) Female sex, family history, radiation exposure (especially in childhood), certain genetic syndromes (MEN2) Risk Factors Cancer Type Hodgkin & NonHodgkin Lymphoma Leukemia Immunosuppression, Epstein-Barr virus (EBV), HIV, family history, certain autoimmune diseases Radiation exposure, benzene exposure, smoking, chemotherapy/radiation therapy for prior cancers, genetic syndromes (Down syndrome, Li-Fraumeni) Screening & Diagnosis What is Screening? Screening tests are regular tests performed to screen for cancer in the general population. Specific tests exist for different types of cancer and they are recommended for different populations at specific ages. Not all cancers have good screening tools, which is why it is essential to pay attention to your body and notice any new or unexplained symptoms.  Screening Recommendations: The screening recommendations below are based on evidence from American and Canadian Cancer societies. Specific screening guidelines in Iran were not used for the creation of this table. Lung cancer screening is not specifically implemented in Iran but should be strongly considered for high-risk individuals, especially given the significant smoking prevalence in Iran.  Cancer Type Screening Test Start-End Age, Frequency Special Considerations Breast Mammography 40-75, every 1-2 years Consider ongoing mammography for individuals examinations anymore, Colon FIT, Colonoscopy 50-75, every 2 If >75. not Breast selfrecommended years for FIT vs. every 10 years for colonoscopy Cervical Pap Smear, HPV Testing 25-65, every 3 years first-degree relative with colon cancer, start screening at 40 or 10 years before the age of onset of cancer in relative.  In sexually active individuals. HPV testing has not been widely implemented but can eventually replace Pap smears. Lung Low-dose CT 50-80, every year Only in high-risk individuals, typically defined as those with 20 pack-year smoking history.   Early Signs & Symptoms: Recognizing the early symptoms of cancer can be very helpful as often, the earlier a cancer is diagnosed, the better the treatment options are. However, the early symptoms of many cancers are also nonspecific and overlap with benign conditions. Therefore, additional investigations are essential to rule out serious causes. The following symptoms and investigations are often performed for the cancers listed below.  Cancer Type Signs & Symptoms Recommended Investigations Breast Palpable lump, skin changes, nipple discharge, breast pain Mammography, ultrasound, MRI, biopsy  Colorectal Rectal bleeding, change in bowel habits, abdominal pain, unexplained iron-deficiency anemia  Colonoscopy, CT colonography Lung Persistent cough, hemoptysis, shortness of breath, chest pain, recurrent pneumonia with nonresolving symptoms Chest x-ray, CT chest, bronchoscopy Prostate Difficulty voiding, weak urine stream, nocturia, hematuria  PSA, digital rectal exam, transurethral prostate biopsy Bladder Visible painless hematuria, microscopic hematuria on urine tests, frequency, urgency, dysuria Urinalysis, urine cytology, cystoscopy, CT urography Endometrial Postmenopausal bleeding, abnormal uterine bleeding in premenopausal women (abnormal flow, duration, or any abnormality per patient), pelvic pain Endometrial biopsy (gold standard), additional investigations include pelvic exam and transvaginal ultrasound Ovarian Abdominal bloating or fulness, early satiety, urinary urgency/frequency, pelvic pain  NOTE: Symptoms are often vague and related to mass effect, consider investigations in women with risk factors (e.g. nulliparous, history of endometriosis) Pelvic exam, transvaginal ultrasound, MRI pelvis, CA-125 levels Cervical Abnormal vaginal bleeding (postcoital, intermenstrual, Pelvic exam, colposcopy with biopsy, HPV testing postmenopausal), unusual vaginal discharge, pelvic pain, dyspareunia Stomach Early satiety, indigestion, mild epigastric pain, unintentional weight loss, anemia Melanoma Changing mole with pigmentation, irregular borders, raised lesion Upper endoscopy with biopsy, abdominal imaging Skin exam, excisional biopsy Leukemia Fatigue, bruising, fever, weight bleeding, loss, pallor, lymphadenopathy, bone pain Lymphoma Painless lymphadenopathy, fever, weight loss, CBC with differential, peripheral smear, bone marrow biopsy drenching night sweats, pruritis, fatigue Genetic Testing for Inherited Risk of Cancer: CBC, lymph node biopsy, bone marrow, PET-scan Genetic testing can be performed to assess for specific changes in one’s DNA that may increase the risk of developing cancer27. Not everyone, however, is a great candidate for genetic testing as interpretation of the results is highly dependent on the initial context of the individual. For example, a positive genetic testing result for an individual with a high-risk family history of breast cancer is much more significant than an individual with no family history as some genetic changes are spontaneous and may not actually have any clinical consequences.  For certain populations, genetic testing is strongly recommended. This includes patients with triple-negative breast cancer, ovarian cancer, pancreatic adenocarcinoma, colorectal cancer before the age of 50, metastatic prostate cancer, or male breast cancer. Knowing the specific genes involved in the propagation of these cancers can be helpful in selecting treatment as well as identify whether there are any hereditary patterns to their disease, which may affect their relatives.  For individuals with a “family history” of cancer, again only a select population are actually recommended to undergo testing. There are specific patterns of disease propagation that suggest a hereditary cancer syndrome. The features include cancer diagnosed at a young age (often before the age of 50), several different types of cancer in the same patient, similar cancer in multiple family members (especially first-degree relatives), or rare types of cancer (such as male breast cancer). In order to determine whether you would benefit from genetic testing for cancer, you should visit a genetic counsellor or a physician with specialty in genetics27.  References: is cancer?. NCI. (2021, October 11). https://www.cancer.gov/about

 

1. What cancer/understanding/what-is-cancer  

​

2. Metastatic cancer: When cancer spreads. https://www.cancer.gov/types/metastatic-cancer  NCI. (2025, January 17).

 

3. Marino, P., Mininni, M., Deiana, G., Marino, G., Divella, R., Bochicchio, I., ... & Sanseverino, F. (2024). Healthy lifestyle and cancer risk: modifiable risk factors to prevent cancer. Nutrients, 16(6), 800.

 

4. Cancer Care Ontario, Occupational Cancer Research Centre. (2017). Burden of occupational cancer in Ontario: Major workplace carcinogens and prevention of exposure. Toronto: Queen’s Printer for Ontario.

 

5. Prevention. Hepatitis B Foundation | Baruch S. Blumberg Institute. (n.d.). https://tinyurl.com/4wrhzytc facts.

 

6. Mayo Foundation for Medical Education and Research. (2023, August 25). HPV vaccine:

Get the Mayo Clinic.

https://www.mayoclinic.org/diseases-conditions/hpv-infection/indepth/hpv-vaccine/art-20047292  

 

7. Helicobacter pylori (H. pylori) and cancer. NCI. (2023, April 12). https://www.cancer.gov/aboutcancer/causes-prevention/risk/infectious-agents/h-pylori-fact-sheet#does-treatment-ofh-pyloriinfection-reduce-the-risk-of-gastric-cancer  

 

8. Ishida, K., & Hsieh, M. H. (2018). Understanding urogenital schistosomiasis-related bladder cancer: an update. Frontiers in medicine, 5, 223.

 

9. Went, M., Sud, A., Mills, C., Hyde, A., Culliford, R., Law, P., ... & Houlston, R. (2024). Phenomewide Mendelian randomisation analysis of 378,142 cases reveals risk factors for eight common cancers. Nature Communications, 15(1), 2637.

 

10. Rintala, S., Dahlstrom, K. R., Franco, E. L., & Louvanto, K. (2023). A synthesis of evidence for cancer-specific screening interventions: Review. Preventive Medicine, 167, 107395. A Preventive Medicine Golden Jubilee

 

11. Seyedkanani, E., Hosseinzadeh, M., Mirghafourvand, M., & Sheikhnezhad, L. (2024). Breast cancer screening patterns and associated factors in Iranian women over 40 years. Scientific Reports, 14(1), 15274.

 

12. Smith, R. A., Andrews, K. S., Brooks, D., Fedewa, S. A., Manassaram‐Baptiste, D., Saslow, D., & Wender, R. C. (2019). Cancer screening in the United States, 2019: A review of current American Cancer Society guidelines and current issues in cancer screening. CA: a cancer journal for clinicians, 69(3), 184-210.

 

13. Perkins, R. B., Wentzensen, N., Guido, R. S., & Schiffman, M. (2023). Cervical cancer screening: a review. Jama, 330(6), 547-558.

 

14. Nahvijou, A., Daroudi, R., Tahmasebi, M., Amouzegar Hashemi, F., Rezaei Hemami, M., Akbari Sari, A., ... & Zendehdel, K. (2016). Cost-effectiveness of different cervical screening strategies in Islamic Republic of Iran: a middle-income country with a low incidence rate of cervical cancer. PloS one, 11(6), e0156705.

 

15. Moyer, V. A., & US Preventive Services Task Force*. (2014). Screening for lung cancer: US Preventive Services Task Force recommendation statement. Annals of internal medicine, 160(5), 330-338.

 

16. Lam, D. C. L., Liam, C. K., Andarini, S., Park, S., Tan, D. S., Singh, N., ... & Yang, P. C. (2023). Lung cancer screening in Asia: an expert consensus report. Journal of Thoracic Oncology, 18(10), 1303-1322.

 

17. Coll, P. P., Korc‐Grodzicki, B., Ristau, B. T., Shahrokni, A., Koshy, A., Filippova, O. T., & Ali, I. (2020). Cancer prevention and screening for older adults: part 2. Interventions to prevent and screen for breast, prostate, cervical, ovarian, and endometrial cancer. Journal of the American Geriatrics Society, 68(11), 2684-2691.

 

18. Koo, M. M., Swann, R., McPhail, S., Abel, G. A., Elliss-Brookes, L., Rubin, G. P., & Lyratzopoulos, G. (2020). Presenting symptoms of cancer and stage at diagnosis: evidence from a crosssectional, population-based study. The Lancet Oncology, 21(1), 73-79.

 

19. Bleyer, A. (2009, June). CAUTION! Consider cancer: common symptoms and signs for early detection of cancer in young adults. In Seminars in oncology (Vol. 36, No. 3, pp. 207-212). WB Saunders.

 

20. Schwartzberg, L., Broder, M. S., Ailawadhi, S., Beltran, H., Blakely, L. J., Budd, G. T., ... & Yermilov, I. (2022). Impact of early detection on cancer curability: A modified Delphi panel study. PLoS One, 17(12), e0279227.

 

21. Voelker, R. (2025). What Is Prostate Cancer?. JAMA, 334(11), 1032-1032.

 

22. DeGeorge, K. C., Holt, H. R., & Hodges, S. C. (2017). Bladder cancer: diagnosis and treatment. American family physician, 96(8), 507-514.

 

23. Grossman, D. C., Curry, S. J., Owens, D. K., Barry, M. J., Davidson, K. W., Doubeni, C. A., ... & US Preventive Services Task Force. (2018). Screening for ovarian cancer: US preventive services task force recommendation statement. Jama, 319(6), 588-594.

 

24. Gbenjo, J. T., McCrary, G. L., & Wilson, S. E. (2023). Leukemia: What primary care physicians need to know. American Family Physician, 107(4), 397-405.

 

25. Shephard, E. A., Neal, R. D., Rose, P. W., Walter, F. M., & Hamilton, W. (2015). Symptoms of adult chronic and acute leukaemia before diagnosis: large primary care case-control studies using electronic records. The British Journal of General Practice, 66(644), e182.

 

26. Cheson, B. D., Fisher, R. I., Barrington, S. F., Cavalli, F., Schwartz, L. H., Zucca, E., & Lister, T. A. (2014). Recommendations for initial evaluation, staging, and response assessment of Hodgkin and non-Hodgkin lymphoma: the Lugano classification. Journal of clinical oncology, 32(27), 3059-3067.

 

27. Genetic testing fact sheet. Genetic Testing Fact Sheet - NCI. (2024, April 18). https://www.cancer.gov/about-cancer/causes-prevention/genetics/genetic-testing-factsheet#who-should-consider-genetic-testing-for-inherited-cancer-risk  

Other Organizations used:

1. World Health Organization (WHO). Cancer Fact Sheets.

2. National Cancer Institute (NCI). Cancer Causes and Risk Factors.

3. American Cancer Society (ACS). Risk Factors by Cancer Type.

4. Cancer Care Ontario. Cancer Prevention Guidelines.

5. Canadian Cancer Society. Risk Factors for Cancer.

6. International Agency for Research on Cancer (IARC). Monographs on the Identification of Carcinogenic Hazards. 

BY​

NIKI ESFAHANIAN, MD  |  ELNAZ ASSADPOUR, MD