Background
Methods
Recruitment of the participants for the study and processing of the samples
Analysis of sequence variants
Immuno expression of p53, p21 and MDM2
Analysis of hotspot regions of KRAS, BRAF and PIK3CA
Statistical analysis
Results
Baseline characteristics of the study participants
Characteristics | Total Number of patients | Number of patients with Wild type TP53 | Number of patients with mutated TP53 | Number of healthy controls |
---|---|---|---|---|
Ethnicity | ||||
Sinhalese | 25 | 18 | 7 | 24 |
Tamil | 1 | 1 | 0 | 5 |
Muslims | 2 | 2 | 0 | 0 |
Burgher | 2 | 0 | 2 | 1 |
Age at study entry | ||||
< 40 years | 1 | 1 | 0 | 9 |
40–60 years | 14 | 11 | 3 | 13 |
> 61 years | 15 | 10 | 5 | 8 |
Body Mass Index | ||||
Underweight | 2 | 2 | 0 | 2 |
Ideal | 9 | 7 | 2 | 9 |
Overweight | 5 | 4 | 1 | 4 |
Pre obese | 10 | 6 | 4 | 11 |
Obese | 4 | 2 | 2 | 4 |
Tumour type | ||||
Invasive Ductal Carcinoma | 29 | 20 | 9 | N/A |
Invasive Lobular Carcinoma | 1 | 1 | 0 | N/A |
Breast affected | ||||
Left | 11 | 7 | 4 | N/A |
Right | 17 | 13 | 4 | N/A |
both | 2 | 1 | 1 | N/A |
Menstrual status | ||||
Pre menopausal | 7 | 5 | 2 | 19 |
Post menopausal | 23 | 16 | 7 | 11 |
Pregnancy history | ||||
Nulliparous | 7 | 4 | 3 | 9 |
1–3 children | 21 | 16 | 5 | 20 |
> 3 children | 2 | 1 | 1 | 1 |
Breast Feeding history (Total) | ||||
No breast feeding | 7 | 4 | 3 | 9 |
< = one year | 4 | 3 | 1 | 8 |
> one year | 18 | 13 | 5 | 13 |
History of cancer | ||||
Previous history | 6 | 3 | 3 | N/A |
Family history | 11 | 8 | 3 | N/A |
Codon 72 polymorphism | ||||
Arginine | 12 | 10 | 2 | 12 |
Proline | 7 | 2 | 5 | 5 |
Arginine/ Proline | 11 | 9 | 2 | 13 |
Characteristics | Total Number of patients | Number of patients with Wild type TP53 | Number of patients with mutated TP53 | Number of healthy controls |
---|---|---|---|---|
Sex | ||||
Male | 14 | 12 | 2 | 11 |
Female | 7 | 2 | 5 | 10 |
Ethnicity | ||||
Sinhalese | 19 | 12 | 7 | 17 |
Tamil | 1 | 1 | 0 | 4 |
Muslims | 1 | 1 | 0 | 0 |
Age at study entry | ||||
30–60 years | 9 | 7 | 2 | 16 |
> 60 years | 12 | 7 | 5 | 5 |
Body Mass index | ||||
Under weight | 2 | 2 | 0 | 1 |
Ideal Weight | 11 | 5 | 5 | 8 |
Overweight | 6 | 4 | 2 | 7 |
Pre obese | 2 | 2 | 0 | 3 |
Obese | 0 | 0 | 0 | 2 |
Histological status of cancer | ||||
Well differentiated adenocarcinoma | 3 | 2 | 1 | N/A |
Moderately differentiated adenocarcinoma | 10 | 6 | 4 | N/A |
Poorly differentiated adenocarcinoma | 1 | 1 | 0 | N/A |
Unknown | 7 | 5 | 2 | N/A |
Smoking history | ||||
Yes | 6 | 6 | 0 | 3 |
No | 15 | 8 | 7 | 18 |
Alcohol consumption | ||||
Yes | 9 | 8 | 1 | 6 |
No | 12 | 6 | 6 | 15 |
Betel-quid chewing | ||||
Yes | 10 | 8 | 2 | 3 |
No | 11 | 6 | 5 | 18 |
Codon 72 polymorphism | ||||
Arginine | 6 | 5 | 1 | 6 |
Proline | 6 | 3 | 3 | 5 |
Arginine/ Proline | 9 | 6 | 3 | 10 |
Analysis of TP53 sequence variants
No | HGVS Nomenclature | Location | Mutation type | No. of carriers in the study cohort | Novel or reported and the code reported in databases for reported variants | *Pathogenicity prediction: In-silico or functional | Conclusion | ||||
---|---|---|---|---|---|---|---|---|---|---|---|
cDNA | Protein | BC patients (N = 30) | CRC patients (N = 21) | Healthy controls – Males (N = 11) | Healthy controls - Females (N = 30) | ||||||
1 | c.848_849delGC | p.Arg283Hisfs*22 | E8 | F | 1 | 0 | 0 | 0 | Novel | In-silico | Path |
2 | c.851_855delCAGAG | p.Thr284Argfs*20 | E8 | F | 1 | 0 | 0 | 0 | Novel | In-silico | Path |
3 | c.431_433delAGC | p.Gln144del | E5 | IF | 0 | 1 | 0 | 0 | Novel | In-silico | Path |
4 | c.637C > T | p.Arg213* | E 6 | NS | 1 | 1 | 0 | 0 | rs397516436 | In-silico | Path |
5 | c.400 T > G | p.Phe134Val | E5 | M | 1 | 0 | 0 | 0 | COSM43941 | Both | Path |
6 | c.524G > A | p.Arg175His | E 5 | M | 0 | 1 | 0 | 0 | rs28934578, COSM10648 | Both | Path |
7 | c.581 T > G | p.Leu194Arg | E6 | M | 0 | 1 | 0 | 0 | rs1057519998, COSM44571 | Both | Path |
8 | c.730G > T | p.Gly244Cys | E7 | M | 1 | 0 | 0 | 0 | COSM11524 | Both | Path |
9 | c.733G > A | p.Gly245Ser | E7 | M | 0 | 2 | 0 | 0 | rs28934575, COSM6932 | Both | Path |
10 | c.743G > A | p.Arg248Gln | E7 | M | 3 | 0 | 0 | 0 | rs11540652/ COSM10662 | Both | Path |
11 | c.840A > T | p.Arg280Ser | E8 | M | 1 | 0 | 0 | 0 | COSM44171 | Both | Path |
12 | c.844C > T | p.Arg282Trp | E 8 | M | 0 | 1 | 0 | 0 | rs28934574, COSM10704 | Both | Path |
13 | c.626G > A | p.Arg209Lys | E6 | M | 1 | 0 | 0 | 0 | COSM45995 | Both | LP |
14 | c.63C > T | p.Asp21Asp | E 2 | S | 2 | 0 | 0 | 1 | rs1800369 | – | LB |
15 | c.459C > T | p.Pro153Pro | E 5 | S | 0 | 1 | 0 | 1 | rs72661116, COSM43964 | In-silico | LB |
16 | c.903A > G | p.Pro301Pro | E8 | S | 1 | 0 | 0 | 0 | rs72661120/ COSM44165 | In-silico | LB |
17 | c.-140G > A | – | E 1 | 3’UTR | 1 | 2 | 0 | 0 | novel | – | LB |
18 | c.97-29C > A | – | I 3 | I | 1 | 2 | 0 | 3 | rs17883323 | In-silico | US |
19 | c.74 + 16G > C | – | I 2 | I | 0 | 1 | 0 | 0 | Novel | – | LB |
20 | c.74 + 38C > G | – | I 2 | I | 20 | 14 | 6 | 24 | rs1642785 | – | LB |
21 | c.96 + 41_96 + 56delACCTGGAGGGCTGGGG | – | I 3 | I | 28 | 6 | 11 | 27 | rs59758982 | – | LB |
22 | c.97-52G > A | – | I3 | I | 0 | 0 | 0 | 1 | rs540683791 | – | LB |
23 | c.782 + 72C > T | – | I 7 | I | 11 | 9 | 7 | 9 | rs12947788 | – | LB |
24 | c.782 + 92 T > G | – | I 7 | I | 11 | 9 | 7 | 9 | rs12951053 | – | LB |
25 | c.75-42G > A | – | I 2 | I | 0 | 0 | 1 | 0 | Novel | – | LB |
26 | c.782 + 79C > T | – | I 7 | I | 0 | 0 | 1 | 0 | Novel | – | LB |
27 | c.673-36G > C | – | I 6 | I | 0 | 1 | 0 | 0 | rs17880604 | In-silico | B |