Cervix smear abnormalities: linking pathology data in female twins, their mothers and sisters

Abstract

Mass screening for cervical cancer precursors has decreased the incidence of cervical cancer in several countries, including the Netherlands. Persistent infections of certain types of human papillomavirus are strongly associated with the development of cervical cancer. A number of factors may affect the liability to infection and subsequent progression to cervical intraepithelial neoplasia and cancer. This paper examines whether genetic factors are involved in explaining individual differences in liability. Data of 3178 women registered with the Netherlands Twin Register were successfully linked to the nationwide Dutch Pathology database that contains all results of mass screening for cervical cancer. The data from mono-and dizygotic twins and their female relatives were used to disentangle the influence of heritable and environmental factors on cervix smear abnormalities. Results showed that differences in cervix smear results clustered within families and resemblance was stronger in monozygotic twins (correlation 0.37, 95% confidence interval: 0.12-0.58) compared with other first-degree relatives (correlation 0.14, 95% confidence interval: À0.01-0.29). The familial clustering for an abnormal cervix smear is due to shared genetic factors that explain 37% of the variance in liability. The largest proportion of the variation in cervical smear abnormalities is due to unique environmental factors.

The Roles of Genetic and Environmental Factors on Risk of Cervical Cancer: A Review of Classical Twin Studies

“…Of these, 12 appeared to have utilized a classical twin design and examined the risk of cervical cancer and its precursor lesions, and thus were selected to undergo a full-text review. After a full-text review, 9 of the 12 articles were excluded; two did not include twin pairs (Magnussen, Lichtenstein, & Gyllensten, et al, 1999;Magnussen, Sparen, & Gyllensten, 2000), five did not utilize a classical twin design but evaluated twinning itself as a risk factor (Braun, Ahlbom, Floderus, Brinton, & Hoover 1995;Hemminki & Li, 2002;Iversen, Tretli, & Kringlen, 2001;Neale, Mineau, Whiteman, Brownbill, & Murphy, 2005;Neale et al, 2004), one reported results aggregated for all cancers, not specifically cervical cancer (Verkasalo, Kaprio, Koskenvuo, & Pukkala, 1999), and one did not report data on dizygotic pairs separately from other first-degree relatives (Vink et al, 2011). Therefore, three articles met our inclusion criteria (Ahlbom et al, 1997;Lichtenstein et al, 2000;Thomsen, Jochumsen, & Mogensen, 2006).…”

Genetic susceptibility to cervical cancer: role of common polymorphisms in apoptosis-related genes

“…Additionally, the risk of developing cervical cancer was found to be approximately twofold higher among biological first-degree relatives of cervical cancer patients, compared to their nonbiological relatives [48]. Furthermore, a recent large-scale study showed that monozygotic twins shared significantly more similar results in cervical smear test compared to dizygotic twins and other first-degree relatives [49]. Based on these epidemiological studies, the genetic heritability of cervical smear abnormality and invasive cervical cancer has been determined as 37 and 27 %, respectively [49,50].…”

“…Furthermore, a recent large-scale study showed that monozygotic twins shared significantly more similar results in cervical smear test compared to dizygotic twins and other first-degree relatives [49]. Based on these epidemiological studies, the genetic heritability of cervical smear abnormality and invasive cervical cancer has been determined as 37 and 27 %, respectively [49,50]. The genetic heritability of cervical cancer is therefore higher than that for colorectal and lung cancers.…”

The Netherlands Twin Register: Longitudinal Research Based on Twin and Twin-Family Designs

“…Information on chorionicity through record linkage as well as access to tissue samples was available from in the Pathological Anatomy National Automatic Archive (PALGA), a nationwide network and register of histopathology and cytopathology database and biobank. Other projects that made use of the PALGA database include studies on triplets and a study of cervix smear abnormalities (Lamb et al, 2012;van Beijsterveldt et al, 2016;Vink et al, 2011). Valuable information can also be obtained by linking the NTR databases to national population-based registers such as the cancer registration in the Netherlands.…”