الفهرس 
TitleOnly 14 pages are availabe for public view
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Abstract
Breast cancer is the most frequently diagnosed cancer among females, It is also the
leading cause of cancer death in women worldwide.
Several risk factors can contribute to the increased incidence of breast cancer which
include family history of breast cancer, Reproductive factors as (age of menarche and
menopause), lifestyle, hormonal therapy and some environmental factors. In addition some
protective factors may reduce breast cancer risk as breast feeding and physical activity.
Several genetic factors have been implicated in increasing the risk of breast cancer as
the missense single nucleotide polymorphism I157T that occurs in the FHA domain of
CHEK2 and The R213H polymorphism of the SULT1A1gene.
The aim of the current study was to study the association of CHEK2 I157T and
SULT1A1 R213H with breast cancer among Egyptian female patients.
The study included 50 breast cancer female patients having pathologically proven
invasive ductal carcinoma. The patients will be recruited from the Cancer Management and
Research Department, Medical Research Institute, Alexandria University. The study also
included 100 healthy volunteers as control group.
All patients were subjected to:
1. Full history taking including: personal data, medical history, pregnancy history,
family history of cancer.
2. Clinical examination.
3. Molecular genetic testing for CHEK2 I157T and SULT1A1 R213H using PCRRFLP
for the patients and the controls
The results of the present study were as follows:
1. The age of the studied patients ranged from 38 to 77 years (mean 53.46 years)
2. Thirty eight patients (76%) were passive smokers while 12 patients (24%) were
non-smokers(and didn’t report a history of exposure to constant smokers). In
the control group 69% were passive smokers and 31% were non-smokers.
3. The BMI of breast cancer patients was: mean± SD (34.80±5.89) (95% CI for
mean 33.12-36.48) and in the control group, the BMI (95% CI for mean 29.64-
31.32), also When stratifying the cases and controls to obese and overweight
groups the following was found: the obese group represented 84% of the cases
compared to 60% of the control while the overweight group represented 14%
in the cases compared to the control 32% the results were statistically
significant with P value = 0.011.
4. DM type 2 was reported in 12% of patients and 21% of the control group the
result was statistical significant with p value = 0.034, hypertension was
Summary
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reported in 28% of cases and 21 % of the control, the result was statistically
nonsignificant with p value = 0.453
5. A positive family history for breast cancer was found in 20 % of cases in the
form of (4% first degree relatives, 14% second degree relatives and 1% had
both first and second degree relatives affected with BC).
6. A positive family history for other cancers included (, colon cancer, leukemia,
lung, brain,uterus, liver, kidney, thyroid gland, prostate, adrenal gland cancer)
was found in 20 % of cases in the form of (12% first degree relative with 2
coloncancer,2 leukemia,uterine cancer,liver and prostate cancer and 8% second
degree relatives who had adrenal gland cancer,2 brain,kidney, 2
lung,leukemia,thyroidand liver cancer).
7. Age of Menarche of breast cancer patients ranged from (10-15years) (mean
11.53-12.15) while in the control group the age of menarche ranged from(11-
14yeras) (mean 11.69-12.00).
8. Menopause was reported in 78% of the patients group(mean 44.8 ± 7.4).while
in the control group 44%, comparison between the two groups showed
statistical significant
9. A history of notmal Breast feeding was reported by 82 % of the BC patient
group compared to 93% in the controls. Comparison between the two groups
showed statistical non significant
10. In the BC patients group, 38% reported the use of contraceptive pills compared
to 16% of the control Comparison between the two groups showed statistical
significant
11. Hormone replacement therapy HRT was reported in 30% of BC patients There
wasn’t any reports of HRT use among the control group. the result was
statistical significant
12. Tumor characteristics:
• The Age of onset mean = 47.05 -51.99
• Tumor size was (3.5*4.3 ± 1.6*2) (mean 3.2 *4 - 4.5*6.2)
• The tumor site was 44% Left Side and 56% Right Side
• The pathology of cancer was 98% Invasive Ductal Carcinoma and 2%
Invasive Ductal & Lobular Carcinoma
• The receptors that included ER, PR and Her2R were found to be (88% ER
+ve and 12% -ve), PR (80% having PR+ve and 20% -ve) and (40% Her2R +v
and 60% -ve) in the patients group
• The stage of cancer was (86% stage II and 14% stage III)
• Metastasis: 18% of the patients had Metastasis to uterus, bone, liver,
lymphoma, brain and lung.
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• Vascular invasion: 82% had Vascular invasion
13. The CHEK2 I157T genotype, in the patients group 19 (38%) patients had a
wild genotype, 30 (60%) were heterozygotes and one (2%) with the variant
genotype. In the control group 53 (53%) carried the wild genotype, 47 (47%)
were hetero genotype and no cases with the variant genotype. There was
statistical significant difference between distribution of CHEK2 I157T
genotype among patients and controls (P=0.039).
• CHEK2 Isoleucin allele frequency, in the patients group was 68% while
threonine allele frequency was 32%. In the control group Isoleucin allele
frequency 77% while threonine allele frequency was 23%. There was a
statistically significant difference between distribution of CHEK2 I157T allele
frequency among patients and controls.
• The wild type genotype was found in 36.6% ER positive patients compared to
its presence in 44.4% of the ER negative patients. The hetero type was found
in 61% ER positive patients and in 55.6% ER negative patients The variant
genotype was found in 2.4% ER positive patients compared to its presence in
0% of the ER negative patients
• The wild type genotype was found in 36.4% PR positive patients compared to
its presence in 50% of the PR negative patients. The hetero type was found in
61.4% PR positive patients and in 50% PR negative patients The variant
genotype was found in 2.3% PR positive patients compared to its presence in
0% of the PR negative patients.the result is statistically nonsignificant
• The wild type genotype was found in 38.8% IDC patients compared to its
presence in 0% of the ID&LC patients. The hetero type was found in 59.2%
IDC patients compared to its presence in 100% of the ID&LC patients. The
variant genotype was found in 2% IDC patients compared to its presence in
0% of the ID&LC patients
• The wild type genotype was found in 37.2% stage 2 patients compared to its
presence in 42.9% of the stage 3 patients. The hetero type was found in 60.5%
stage 2 patients compared to its presence in 57.1% of the stage 3 patients. The
variant genotype was found in 2.3% stage 2 patients compared to its presence
in 0% of the stage 3 patients.the result is statistically nonsignificant
14. The SULT1A1 R213H genotype in the patients group included twenty one
(42%) patients with Arg/Arg genotype, twenty one (42%) with Arg/His
genotype and eight (16%) with His/His genotype. In the control group, fifty
two (52%) had the Arg/Arg genotype, forty three (43%) were Arg/His
genotype and five (5%) had a His/His genotype. There was no statistical
significant difference between distribution of SULT1A1 R213H genotypes
among cases and controls (P=0.069).
• the Arg allele frequency in the patients group was 64% while the His allele
frequency was 36%.In the control group the Arg allele frequency was 36%
while the His allele frequency was 26%. There was no statistical significant
difference between distribution of SULT1A1 allele frequency among cases
and controls.
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• The Arg /Arg genotype was found in 43.9% ER positive patients compared to
its presence in 33.3% of the ER negative patients. The Arg /His was found in
39% ER positive patients and in 55.6% ER negative patients The His /His
genotype was found in17.1% ER positive patients compared to its presence in
11.1% of the ER negative patients.
• The Arg /Arg genotype was found in 43.2% PR positive patients compared to
its presence in 33.3% of the PR negative patients. The Arg /His was found in
40.9% PR positive patients and in 50% PR negative patients The His /His
genotype was found in15.9% PR positive patients compared to its presence in
16.7% of the PR negative patients.
• The Arg /Arg genotype was found in 42.9% IDC patients compared to its
presence in 0% of the ID&LC patients. The Arg /His was found in 42.9% IDC
patients and in 0% ID&LC patients The His /His genotype was found in14.3%
IDC patients compared to its presence in 100% of the ID&LC patients.
• The Arg /Arg genotype was found in 44.2% cancer stage 2 patients compared
to its presence in 28.6% of the stage 3 patients. The Arg /His was found in
39.5% cancer stage 2 patients compared to its presence in 57.1% of the stage
3 patients The His /His genotype was found 16.3% cancer stage 2 patients
compared to its presence in 14.3% of the stage 3 patients
15. By making logistic regression measure the liability for breast cancer, The
overall model was statistically significant (X2= 34.88, p=0.003). The predictors
(age, Marital status, Hormonal Replacement, BMI Categories, Family History
and Sult1A1 / Check2 genetic polymorphisms) were entered by stepwise
approach. Only obesity, positive family history and Chek2 polymorphism
significantly contributed to the development breast cancer. But other predictors
were not significant contributers to the development breast cancer.