Additional file 2: Table S2. of MDM2 promoter polymorphism del1518 (rs3730485) and its impact on endometrial and ovarian cancer risk

MDM2 del158 genotype distribution in EC subgroups. (DOCX 17 kb

Additional file 1: Table S1. of MDM2 promoter polymorphism del1518 (rs3730485) and its impact on endometrial and ovarian cancer risk

MDM2 del158 genotype distribution in OC subgroups. (DOCX 17 kb

Additional file 4: Table S4. of MDM2 promoter polymorphism del1518 (rs3730485) and its impact on endometrial and ovarian cancer risk

Raw data; genotypes for all individuals in study. (XLSX 118 kb

Additional file 3: Table S3. of MDM2 promoter polymorphism del1518 (rs3730485) and its impact on endometrial and ovarian cancer risk

MDM2 del158 genotype distribution among individuals with SNP309TT genitype in EC subgroups. (DOCX 15 kb

C77G in <i>PTPRC</i> (CD45) is no risk allele for ovarian cancer, but associated with less aggressive disease

<div><p>The pan lymphocyte marker CD45 exists in various isoforms arising from alternative splicing of the exons 4, 5 and 6. While naïve T cells express CD45RA translated from an mRNA containing exon 4, exons 4–6 are spliced out to encode the shorter CD45R0 in antigen-experienced effector/memory T cells. The SNP C77G (rs17612648) is located in exon 4 and blocks the exon’s differential splicing from the pre-mRNA, enforcing expression of CD45RA. Several studies have linked C77G to autoimmune diseases but lack of validation in other cohorts has left its role elusive. An incidental finding in an ovarian cancer patient cohort from West Norway (Bergen region, n = 312), suggested that the frequency of C77G was higher among ovarian cancer patients than in healthy Norwegians (n = 1,357) (3.0% vs. 1.8% allele frequency). However, this finding could not be validated in a larger patient cohort from South-East Norway (Oslo region, n = 1,198) with 1.2% allele frequency. Hence, C77G is not associated with ovarian cancer in the Norwegian population. However, its frequency was increased in patients with FIGO stage II, endometrioid histology or an age at diagnosis of 60 years or older indicating a possible association with a less aggressive cancer type.</p></div

Allele frequencies of C77G in different cohorts.

<p>Allele frequencies of C77G in different cohorts.</p

Allelic discrimination plots.

<p>Results of the KASP assay for the Oslo cohort (n = 1,198 ovarian cancer patients) from South-East Norway (left plot) and controls (right plot). RFLP-genotyped patient samples from the Bergen cohort were used as SNP heterozygous and homozygous controls. All samples evaluated by KASP as heterozygous or undetermined were re-analysed by RFLP. Patients C/C: SNP negative, Patients G/C: heterozygous C77G/+, KASP G/C, RFLP C/C: scored as heterozygous with KASP and SNP-negative with RFLP, KASP undetermined, RFLP C/C: scored undetermined with KASP and SNP-negative with RFLP, KASP undetermined, RFLP weak: scored undetermined with KASP and showed only a weak signal with RFLP (added to the SNP-negative group). ΔRn: difference of the normalised fluorescent reporter signals in the KASP assay.</p

Clinicopathologic parameters of the cohorts.

<p>Distribution of FIGO stages (a) and histologic subtypes (b) within the Bergen, Oslo and combined cohorts. Pie charts display both the respective C77G-negative and the C77G-positive patients. (c) Number of SNP carriers within the patient subpopulations with an age at diagnosis < 60 and ≥ 60 years. All P values (<i>χ</i>²) are based on allele frequencies. Significant P values are indicated by asterisks. MAF: minor allele frequency.</p

Flow cytometry of patient samples, RFLP and sequence analysis.

<p>(a) Flow cytometry analysis of ascites fluid derived CD3⁺CD8⁺ TALs from one SNP-negative (+/+) and two C77G-heterozygous (C77G/+) ovarian cancer patients, the latter showing reduced numbers of CD45RA^- cells in ascites fluid. (b) RFLP analysis of four SNP-negative (+/+), two C77G-heterozygous (C77G/+) and the C77G-homozygous (C77G/C77G) patient. Upper bands represent the undigested 155-bp PCR fragment whereas the two lower bands are the <i>Msp</i>I restriction fragments of 83 and 72 bp, when C77G is present. (c) Sequence analysis of PCR products of the homozygous (C77G/C77G), one heterozygous (C77G/+) before and after <i>Msp</i>I digest and one SNP-negative (+/+) patient. Note that sequencing of the heterozygous patient results in a double peak C/G at position 77 favoring G, while after <i>Msp</i>I digest the double peak is reversed.</p

C77G is not associated with patient outcome.

<p>Kaplan-Meier plots of Cancer specific (CS) and overall survival curves for the Bergen (a) and the Oslo (b) cohort, respectively. Survival estimates were calculated using two sided log-rank tests (Mantel-Cox). Censored patients are indicated by ticks.</p