Researchers have identified three genes associated with an increased risk of developing cervical cancer.
Despite the success of screening and vaccination programmes, invasive cervical cancer is still one of the most common malignancies in women globally. Infection with oncogenic high-risk human papillomavirus (HPV) subtypes is necessary for the development of cervical cancer and its precursor cervical intraepithelial neoplasia (CIN). HPV infection is common – with over 70% of people infected over their lifetime. Most infections are cleared through an immune response, yet some women develop persistent HPV infection which subsequently develops into CIN or invasive cervical cancer.
There are a number of host and viral factors that can affect the clearance of HPV and risk of progression to cancer. For example, HPV genotype, HPV genetic and epigenetic variants and also viral load all impact disease outcomes. Host factors such as tobacco smoking, hormonal contraceptives and sexual factors are all suspected to influence exposure and immune response to HPV.
Unfortunately, while studies have reported family aggregation of cervical cancer, researchers have not been able to discriminate between the effects of genes and shared environmental factors. To date, the impact of genetic variation on predisposition to cervical cancer remains unclear.
Genetic association study
In this paper, published in The Lancet Oncology, researchers performed the largest genome-wide exploration of variants associated with cervical cancer to date. The team harnessed the data from the UK Biobank and validated candidate associations in an independent population (FinnGen). The UK Biobank cohort consisted of 273, 377 unrelated European individuals aged 40-69 years.
The data revealed that common variants in three genes – PAX8, CLPTM1L and the HLA region – associated with an increased risk of developing cervical cancer. While the HLA region plays a role in the immune response, PAX8 and CLPTM1L are involved in controlling the body’s responses to early cancerous changes in cells. The team also validated these results in an independent replication set.
While these findings need to be confirmed in larger studies and the biological effects properly examined, they have opened the doors for more personalised screening or treatment approaches in the future.
Dr Sarah Bowden, lead researcher of the study, stated:
“Once genetic testing becomes more widespread, looking at a patient’s genetic information alongside cervical screening could help identify individuals who need close monitoring or treatment.”
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