Polymorphisms in 9q32 and TSCOT are linked to cervical cancer in affected sib-pairs with high mean age at diagnosis

Engelmark, Malin (author): Uppsala universitet,Institutionen för genetik och patologi

Ivansson, Emma (author): Uppsala universitet,Institutionen för genetik och patologi

Magnusson, Jessica (author): Uppsala universitet,Institutionen för genetik och patologi

Gustavsson, Inger (author): Uppsala universitet,Institutionen för genetik och patologi

Wyöni, Per-Ivan (author): Uppsala universitet,Institutionen för genetik och patologi

Ingman, Max (author): Uppsala universitet,Institutionen för genetik och patologi

Magnusson, Patrik (author): Karolinska Institutet,Uppsala universitet,Institutionen för genetik och patologi

Gyllensten, Ulf (author): Uppsala universitet,Institutionen för genetik och patologi

(creator_code:org_t)

2008-04-08
2008
English.
In: Human Genetics. - : Springer Science and Business Media LLC. - 0340-6717 .- 1432-1203. ; 123:5, s. 437-443

Related links:: https://urn.kb.se/re...; show more...; https://doi.org/10.1...; http://kipublication...; show less...

Abstract Subject headings

Cervical cancer is a multifactorial disease influenced by both environmental and genetic factors. We have previously found linkage to 9q32 in a genomewide scan of affected sib-pairs (ASPs) with cervical cancer and to the thymic stromal co-transporter (TSCOT), a candidate gene in this region. Here we examined the contribution of 9q32 and TSCOT to cervical cancer susceptibility using at larger material of 641 ASPs, 278 of which were included in the earlier genome-scan. Since heritable forms of cancer frequently show stronger genetic effects in families with early onset of disease, we stratified the ASPs into two groups based on mean age at diagnosis (MAAD) within sib-pairs. Surprisingly, ASPs with high MAAD (30.5-47.5 years) showed increased sharing at all microsatellite markers at 9q31.1-33.1 and linkage signals of up to MLS = 2.74 for TSCOT SNPs, while ASPs with low MAAD (19-30 years) showed no deviation from random genetic sharing (MLS = 0.00). The difference in allelic sharing between the two MAAD strata was significant (P < 0.005) and is not likely to be explained by the HLA haplotype, a previously known genetic susceptibility factor for cervical cancer. Our results indicate locus heterogeneity in the susceptibility to cervical cancer between the two strata, with polymorphisms in the 9q32 region mainly showing an effect in women with high MAAD.

By the author/editor: Engelmark, Malin; Ivansson, Emma; Magnusson, Jessi ...; Gustavsson, Inge ...; Wyöni, Per-Ivan; Ingman, Max; show more...; Magnusson, Patri ...; Gyllensten, Ulf; show less...

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