| 1. |
- Barnekow, Elin, et al.
(author)
-
A Swedish Familial Genome-Wide Haplotype Analysis Identified Five Novel Breast Cancer Susceptibility Loci on 9p24.3, 11q22.3, 15q11.2, 16q24.1 and Xq21.31
- 2023
-
In: International Journal of Molecular Sciences. - : MDPI AG. - 1661-6596 .- 1422-0067. ; 24:5
-
Journal article (peer-reviewed)abstract
- Most breast cancer heritability is unexplained. We hypothesized that analysis of unrelated familial cases in a GWAS context could enable the identification of novel susceptibility loci. In order to examine the association of a haplotype with breast cancer risk, we performed a genome-wide haplotype association study using a sliding window analysis of window sizes 1–25 SNPs in 650 familial invasive breast cancer cases and 5021 controls. We identified five novel risk loci on 9p24.3 (OR 3.4; p 4.9 × 10−11), 11q22.3 (OR 2.4; p 5.2 × 10−9), 15q11.2 (OR 3.6; p 2.3 × 10−8), 16q24.1 (OR 3; p 3 × 10−8) and Xq21.31 (OR 3.3; p 1.7 × 10−8) and confirmed three well-known loci on 10q25.13, 11q13.3, and 16q12.1. In total, 1593 significant risk haplotypes and 39 risk SNPs were distributed on the eight loci. In comparison with unselected breast cancer cases from a previous study, the OR was increased in the familial analysis in all eight loci. Analyzing familial cancer cases and controls enabled the identification of novel breast cancer susceptibility loci.
|
|
| 2. |
- Barnekow, Elin, et al.
(author)
-
A Swedish Genome-Wide Haplotype Association Analysis Identifies a Novel Breast Cancer Susceptibility Locus in 8p21.2 and Characterizes Three Loci on Chromosomes 10, 11 and 16
- 2022
-
In: Cancers. - : MDPI AG. - 2072-6694. ; 14:5
-
Journal article (peer-reviewed)abstract
- Background: The heritability of breast cancer is partly explained but much of the genetic contribution remains to be identified. Haplotypes are often used as markers of ethnicity as they are preserved through generations. We have previously demonstrated that haplotype analysis, in addition to standard SNP association studies, could give novel and more detailed information on genetic cancer susceptibility.Methods: In order to examine the association of a SNP or a haplotype to breast cancer risk, we performed a genome wide haplotype association study, using sliding window analysis of window sizes 1-25 and 50 SNPs, in 3200 Swedish breast cancer cases and 5021 controls.Results: We identified a novel breast cancer susceptibility locus in 8p21.1 (OR 2.08; p 3.92 x 10(-8)), confirmed three known loci in 10q26.13, 11q13.3, 16q12.1-2 and further identified novel subloci within these three loci. Altogether 76 risk SNPs, 3302 risk haplotypes of window size 2-25 and 113 risk haplotypes of window size 50 at p < 5 x 10(-8) on chromosomes 8, 10, 11 and 16 were identified. In the known loci haplotype analysis reached an OR of 1.48 in overall breast cancer and in familial cases OR 1.68.Conclusions: Analyzing haplotypes, rather than single variants, could detect novel susceptibility loci even in small study populations but the method requires a fairly homogenous study population.
|
|
| 3. |
- Bryant, Patrick, et al.
(author)
-
Exome sequencing in a Swedish family with PMS2 mutation with varying penetrance of colorectal cancer : investigating the presence of genetic risk modifiers in colorectal cancer risk
- 2023
-
In: European Journal of Cancer Prevention. - 0959-8278 .- 1473-5709. ; 32:2, s. 113-118
-
Journal article (peer-reviewed)abstract
- Objective Lynch syndrome is caused by germline mutations in the mismatch repair (MMR) genes, such as the PMS2 gene, and is characterised by a familial accumulation of colorectal cancer. The penetrance of cancer in PMS2 carriers is still not fully elucidated as a colorectal cancer risk has been shown to vary between PMS2 carriers, suggesting the presence of risk modifiers.Methods Whole exome sequencing was performed in a Swedish family carrying a PMS2 missense mutation [c.2113G>A, p.(Glu705Lys)]. Thirteen genetic sequence variants were further selected and analysed in a case-control study (724 cases and 711 controls).Results The most interesting variant was an 18 bp deletion in gene BAG1. BAG1 has been linked to colorectal tumour progression with poor prognosis and is thought to promote colorectal tumour cell survival through increased NF-κB activity.Conclusions We conclude the genetic architecture behind the incomplete penetrance of PMS2 is complicated and must be assessed in a genome wide manner using large families and multifactorial analysis.
|
|
| 4. |
- Forsberg, Anna, et al.
(author)
-
Colonoscopy findings in high-risk individuals compared to an average-risk control population
- 2015
-
In: Scandinavian Journal of Gastroenterology. - : Informa UK Limited. - 0036-5521 .- 1502-7708. ; 50:7, s. 866-874
-
Journal article (peer-reviewed)abstract
- Background and aims: There is clear evidence of reduced morbidity and mortality from regular colonoscopy programs in patients with Lynch syndrome (LS). Today, also individuals with empirically increased risks of colorectal cancer (CRC) are offered colonoscopic surveillance. The aim was to compare the findings at the first screening colonoscopy in LS carriers, and individuals with an increased risk of bowel cancer due to family history of CRC with a control population. Methods: Altogether 1397 individuals with an increased risk for CRC were divided in four risk groups: one with LS carriers and three groups with individuals with different family history of CRC. The findings were compared between the different risk groups and a control group consisting of 745 individuals from a control population who took part in a population-based colonoscopy study. Results: In LS, 30% of the individuals had adenomas and 10% advanced adenomas. The corresponding figures in the other risk groups were 14-24% and 4-7%, compared with 10% and 3% in the control group. The relative risk of having adenomas and advanced adenomas was, compared to controls, significantly higher for all risk groups except the group with the lowest risk. Age was a strong predictor for adenomas and advanced adenomas in both risk individuals and controls. Conclusions: Individuals with a family history of CRC have a high prevalence and cumulative risk of adenomas and advanced adenomas, and screening is motivated also in this risk group.
|
|
