Ovarian cancer is the eighth most common cancer globally, with over 324,000 new cases reported in 2022.1 Despite advances in treatment, it remains one of the leading causes of cancer-related deaths due to challenges in early diagnosis. Current screening methods often yield false positives, leading to invasive procedures, while early-stage detection remains elusive. The disease is influenced by both genetic and lifestyle factors, with smoking identified as a modifiable risk factor for certain subtypes, particularly mucinous ovarian tumours.
Given the increasing focus on preventable risks, this article aims to explore the relationship between smoking and ovarian cancer. Understanding how smoking contributes to the development of specific histological subtypes can inform public health strategies and prevention efforts targeting lifestyle modifications.1,2
Ovarian cancer is classified into three main types based on the cells where it originates: epithelial, germ cell, or stromal. Epithelial ovarian cancer is the most common, accounting for about 90% of cases, and typically affects women over 50. Germ cell tumours arise in egg-producing cells and are more common in younger women, while stromal tumours develop in hormone-producing cells and are relatively rare.2
Symptoms of ovarian cancer are often vague and easily mistaken for less serious conditions. The non-specific nature of these symptoms contributes to the difficulty of early diagnosis. Some common symptoms include:2
Diagnostic methods of ovarian cancer include the CA-125 blood test and a transvaginal ultrasound. The CA-125 test is a blood test measuring levels of the protein cancer antigen 125, which is often elevated in ovarian cancer but can also rise due to benign conditions like endometriosis or menstruation. Since elevated CA-125 levels are also found in other conditions and are not exclusive to cancer, it is unreliable as a standalone test.
It is most effective when combined with imaging (e.g. ultrasound) in symptomatic or high-risk individuals. Ultrasound imaging provides a structural picture of the ovaries, while biopsy remains the definitive diagnostic tool.3,4
Risk factors for ovarian cancer include lifestyle, age, family history, genetic mutations such as BRCA1/2, and reproductive history. Hereditary syndromes like Lynch syndrome also increase susceptibility, emphasising the importance of genetic counselling for high-risk individuals.4
Epithelial ovarian cancer (EOC) is classified into several histological subtypes, including high-grade serous, endometrioid, clear cell, and mucinous carcinoma. These subtypes differ significantly in origin, molecular profile, clinical behaviour, and response to treatment. Understanding these distinctions is essential when examining risk factors such as tobacco use, as not all subtypes are equally affected.
Among the epithelial subtypes, mucinous ovarian carcinoma has the most consistently documented association with cigarette smoking. Epidemiological studies have shown that smokers are at a significantly increased risk of developing mucinous tumours, with some data indicating up to a two-fold increase in incidence compared to non-smokers. This relationship appears to be dose-dependent, with a greater risk associated with higher levels of tobacco exposure.4
Mucinous carcinomas are often diagnosed at an earlier stage but tend to be less responsive to standard platinum-based chemotherapy, resulting in poorer outcomes if diagnosed at an advanced stage. Unlike high-grade serous carcinoma, which is often linked to genetic mutations, mucinous tumours are thought to arise from distinct precursor lesions that may be particularly susceptible to the carcinogenic effects of tobacco.1,5
This specific risk highlights the importance of considering smoking as a relevant environmental factor in ovarian cancer prevention, especially for mucinous variants.
Tobacco smoke contains over 70 known carcinogens, including polycyclic aromatic hydrocarbons (PAH) and nitrosamines, which induce DNA damage and promote tumorigenesis. These compounds circulate systemically, reaching ovarian tissue through blood circulation and forming DNA adducts. Direct evidence of carcinogen exposure has been found in ovarian follicular cells of smokers.6
Biological plausibility focuses on how smoking affects ovarian mucinous cells. PAH can cause malignant changes by increasing mucin production or causing chronic inflammation, promoting mucinous tumours. Smoking changes oestrogen metabolism, possibly influencing hormone-sensitive cancer types, but evidence is inconsistent. 7,8
Tobacco smoke contains a range of carcinogens that can contribute to the development of ovarian cancer through several biological mechanisms. One of the most direct effects is DNA damage.9
Oxidative stress is another important factor. Smoking increases the production of reactive oxygen species, which can damage cellular structures and promote genetic instability. Over time, this may contribute to malignant transformation, particularly in tissues already prone to mutation.
Inflammation also plays a role. Chronic exposure to tobacco can lead to a persistent inflammatory state, which supports tumour development by promoting cell proliferation and reducing the effectiveness of natural repair processes.10
Additionally, smoking has been shown to affect hormone levels, particularly oestrogen metabolism. Since ovarian tissue is hormonally responsive, disruptions in hormonal balance may influence cancer risk in specific subtypes. Finally, cigarette smoke can impair immune function by reducing the activity of immune cells responsible for identifying and eliminating abnormal cells. This may allow early-stage tumour cells to persist and grow unchecked.11
Large-scale epidemiological studies have consistently shown that smoking is associated with an increased risk of mucinous ovarian cancer, while no significant links have been found for other major subtypes.
One of the most notable studies is the Million Women Study, which followed over one million UK women and found that current smokers had a significantly higher incidence of mucinous ovarian cancer compared to non-smokers, with no elevated risk for serous or endometrioid types.6
A clear dose-response relationship has also been observed. Women with a higher lifetime exposure to smoking, measured in pack-years, were found to have a greater risk, particularly for mucinous tumours. For example, those with more than 20 pack-years of smoking exposure had more than double the risk compared to non-smokers, while former smokers showed a reduced but still elevated risk. This suggests that smoking cessation may reverse the increased risk caused by smoking over time.6
Overall, the data strongly support smoking as a modifiable risk factor for mucinous ovarian cancer, reinforcing the need for subtype-specific risk assessment and tailored public health messaging.
Smoking may not only increase the risk of mucinous ovarian cancer but also affect outcomes after diagnosis. Studies suggest that current smokers have lower survival rates and a higher chance of recurrence. This may be due to the negative effects of smoking on the immune system and tissue healing, as well as reduced tolerance to treatment.12
Mucinous tumours already respond poorly to standard chemotherapy. Continued smoking may worsen this by limiting drug effectiveness and increasing treatment complications. While the biological reasons are still being studied, these patterns highlight smoking as a potential factor in disease progression and treatment response.13
Encouraging smoking cessation during diagnosis may improve outcomes. Patients who quit may benefit from better treatment tolerance and fewer complications, which can influence quality of life and survival.
Ovarian cancer is the eighth most common cancer globally. It is a leading cause of cancer deaths due to difficulties in early diagnosis. Current screening methods can produce false positives and often miss early-stage cases. Genetic and lifestyle factors influence the disease, with smoking identified as a modifiable risk factor, especially for mucinous ovarian tumours. Ovarian cancer has three main types: epithelial, germ cell, and stromal. Epithelial ovarian cancer is the most prevalent, mainly affecting women over 50, while germ cell tumours are more common in younger women. Symptoms are often vague, making early diagnosis challenging.
Diagnosis typically involves the CA-125 blood test and transvaginal ultrasound, both of which have limitations when used alone. Risk factors include lifestyle, age, family history, and genetic mutations. Among the epithelial types, mucinous carcinoma has a noted connection with smoking. Epidemiological studies suggest smokers have a significantly higher risk of mucinous tumours, with risks increasing with more extensive tobacco exposure. Smoking contributes to disease through various mechanisms, including DNA damage, oxidative stress, and inflammation. This can affect prognosis and treatment outcomes, as smokers tend to have lower survival rates and higher recurrence chances. Encouraging smoking cessation during diagnosis may improve treatment outcomes and overall survival.
Ovarian cancer cannot be self-diagnosed at home. Confirming an ovarian cancer diagnosis requires several tests and the skills of a specialist.
Several conditions can mimic ovarian cancer, such as ovarian cysts, premenstrual syndrome (PMS), and irritable bowel syndrome (IBS).
More than two-thirds of individuals diagnosed with ovarian cancer are aged 55 or above, and almost half of all cases involve women who are 65 years old or older.
