Why does it matter?

Globally, ovarian cancer ranks as the eighth most prevalent cancer among people assigned as women at birth, contributing to approximately 3.7% of all cases and 4.7% of cancer fatalities in 2020.¹ Scandinavia, Israel, and North America exhibit the highest rates of mortality for ovarian cancer, while Japan and other developing nations have the lowest rates. The five-year survival rate exceeds 75% when cancer is diagnosed before it has spread to other organs, and it decreases to 20% when the cancer has spread to the upper abdomen.²

What is ovarian cancer?

Cancer is a condition where cells undergo a malignant transformation, meaning they start to grow uncontrollably and no longer behave like normal cells. This rapid, disorganised growth can lead to the formation of masses called malignant tumours. Cancer can stay in one place (localised tumour) or spread to other parts of the body through the blood or lymphatic system (metastasis).²

Ovarian cancer is a cancer that develops in the almond-shaped reproductive organs in females where eggs, or ova, are made (ovaries), within either of the two tubes that carry eggs from the ovaries to the uterus (fallopian tubes), or in the membrane that coats the pelvis and abdominal cavity and envelops all abdominal organs (peritoneum).³

Major risk factors

A risk factor is anything that increases the chance of getting a disease like cancer. Various cancers possess distinct risk factors. Certain risk factors, such as smoking, are modifiable, while a person's age or family background are fixed factors.

However, possessing one or more risk factors does not guarantee that you will develop the disease. Additionally, certain individuals who contract the illness may lack any identifiable risk factors. Researchers have identified various risk factors that could elevate the likelihood of developing epithelial ovarian cancer. These risk factors are not relevant to other rarer forms of ovarian cancer, such as germ cell tumours and stromal tumours.

Increasing age

Most ovarian cancer cases occur in women over 50. The likelihood of developing ovarian cancer increases as one gets older. Ovarian cancer is uncommon in individuals under 40 years old. The majority of ovarian cancers arise following menopause. About 50% of ovarian cancers occur when aged 63 years and above.

Family history of ovarian cancer, breast cancer or colorectal cancer

Ovarian cancer may occur in familial lines. Your risk of ovarian cancer rises if your mother, sister, or daughter has (or had) ovarian cancer. The risk increases further with the number of relatives who have ovarian cancer. A higher risk of ovarian cancer can also stem from your father's lineage.

A family background of certain other cancer types, like breast and colorectal cancer, is associated with a higher risk of ovarian cancer. This is because these cancers may result from a hereditary mutation (alteration) in specific genes, leading to a family cancer syndrome that heightens the risk of ovarian cancer.⁴

Genes associated with ovarian cancer

What are genes?

Genes contain “chemical instructions” that instruct our body’s cells on what actions to take. They regulate our development, our appearance, and the functioning of our bodies. Humans possess approximately 25,000 pairs of genes within each cell. One version of each gene pair is passed down from both our parents.

What are gene variants?

The majority of cancers arise from genetic changes due to DNA damage occurring in an individual cell. These are referred to as "somatic" variants and do not occur within families. Occasionally, mutations occur in genes that can prevent the gene from functioning correctly. This is referred to as a ‘mutation’ or ‘pathogenic gene variant’ and can lead to disease in certain instances.⁵

BRCA1 and BRCA2 genes

Ovarian cancer resulting from an inherited gene mutation is referred to as 'hereditary cancer'. If you receive a gene variant that leads to hereditary cancer, it indicates you have an increased likelihood of developing cancers associated with that gene.

BRCA1 and BRCA2 are genes that act as tumour suppressors, meaning they prevent cells from multiplying or spreading too much. All individuals possess these genes. Alterations or mutations (changes in DNA) in these genes result in improper functioning, causing cells to multiply uncontrollably, increasing the chance that lead to cancer.^5,6

The BRCA1 and BRCA2 genes typically aid in preventing cancer, but when an individual inherits a variant that disrupts the function of either gene, their protection against cancer decreases. Anyone with ovaries has roughly a 2% chance of developing ovarian cancer.

 Nevertheless, individuals who receive a defective

• BRCA1 gene face a heightened risk of up to 40% of developing ovarian cancer during their lifetime
• BRCA2 gene face an elevated risk of 18% of developing ovarian cancer during their lives⁵

Having children at a later age or not experiencing a complete-term pregnancy

Never being pregnant or having children late increases the risk of getting ovarian cancer.

Early menstruation or late menopause results in more ovulations, leading to a higher risk. Individuals who experience their initial full-term pregnancy after the age of 35 or who have never completed a pregnancy have an increased risk of developing ovarian cancer. Women who use oestrogens alone or alongside progesterone post-menopause have a higher risk of ovarian cancer than those who have never used hormones.⁴

Does hormone replacement therapy (HRT) increase the cancer risk? 

What is HRT?

HRT is a therapy that can alleviate menopause symptoms by altering hormone levels in the body. Hormones function as chemical signals. They can influence aspects such as growth, fertility, and mood. Menopause is a natural aspect of ageing during which menstruation stops.

Throughout menopause, the ovaries (reproductive part of females) begin to generate lower amounts of the hormone oestrogen. The majority of individuals undergoing menopause will face certain symptoms. These may last for months or years, can be troublesome, and majorly affect everyday tasks. HRT can assist in minimising them.⁷

• Hormone replacement therapy (HRT) marginally raises the risk of developing breast cancer, ovarian cancer, and occasionally uterine cancer. However, the risk is minimal
• HRT is an efficient remedy for menopause symptoms. For many individuals, the advantages of using HRT surpass the potential risks
• Your physician can prescribe HRT and assist you in making an informed decision about what is best for you⁷

Other possible risk factors

1. Obesity (Increased body weight) 

Obesity is associated with an increased risk of various types of cancer. The existing data on the link between obesity and ovarian cancer risk is not fully understood. Obese individuals (defined as having a body mass index [BMI] of 30 or above) may face an increased risk of ovarian cancer, although this does not necessarily include the more aggressive forms, like high-grade serous cancers. Obesity might also adversely influence the overall survival of the person diagnosed with ovarian cancer.⁴

2. Endometriosis

Endometriosis is known as when your tissue lining the uterus grows outside of your uterus. Main symptoms include pain in the lower abdomen, called the pelvic region. Individuals with endometriosis had an average diagnosis age of approximately 36. In general, women suffering from endometriosis had a risk of ovarian cancer that was over four times greater than that of those who did not have endometriosis. This equated to roughly 10 additional cases for every 10,000 women.⁸

3. Use of fertility drugs

In the majority of people assigned women at birth, most studies show that fertility drugs are not significantly responsible for an increase in the risk of developing ovarian cancer. This includes findings from two large, well-controlled studies. However, questions remain regarding the effects on some populations, including women with BRCA1 or BRCA2 mutations, those who have never conceived after reproductive therapy, those with borderline ovarian tumours, and long-term users of fertility medications. Furthermore, long-term effects are still being studied, as it might be too soon to establish a link between fertility drug use and the risk of ovarian cancer since many of the individuals exposed are only now reaching the age where ovarian cancer typically develops.⁹

4. Smoking

Smoking does not elevate the overall risk of ovarian cancer, but it is associated with a higher risk for the mucinous subtype (referred to in which the tumour cells produce a large amount of mucus).⁴

Summary

Many health conditions are influenced by a range of risk factors. Certain aspects, like heredity and age, are beyond our control, whilst others, such as smoking, obesity, and hormone replacement medication, may be changed. Recognising these risk factors is critical since the early identification of many illnesses is sometimes difficult. Recognising both manageable and uncontrollable risks helps with better monitoring, prevention, and informed lifestyle decisions, helping reduce the overall risk of disease.