Reproductive Factors and Common Genetic Mutations Associated with Breast Cancer Risk in Gaza Strip

Abstract

Context and objective: BRCA1 and BRCA2 are the two principal hereditary breast cancer susceptibility genes, and the incidence of their mutations among breast cancer patients in Gaza Strip is unknown. The objective was to study the incidence of the most common BRCA1 and BRCA2 mutations in Gaza Strip patients with breast cancer, to establish genetic profiles. Design and setting: The study is a cross sectional. The patients group size was 122 patients and was selected fromEl-ShifaHospital and The European Hospital in Gaza Strip. The control sample size was 55 healthy married women. Methods: One hundred and seventy seven participants were interviewed face to face using a validated questionnaire. In addition to their demographic characteristics, ninety four participants were manage to genetic testing for BRCA1 and BRCA2 mutations; Peripheral blood samples were collected, genomic DNA was extracted for the detection of 185delAG and 5382insC mutations inBRCA1, and 6174delT mutation in BRCA2, a multiplex polymerase chain reaction (PCR) was performed with allele-specific oligonucleotide primers. In this method, two primers (one specific for the mutant, and one specific for the wild-type allele) were designed. All data were analyzed using the Statistical Package for the Social Sciences (SPSS Inc.) version 16.0. Results: There were statistically significant differences among study population with respect to age of women (P=0.00), BMI (P=0.03), number of pregnancies (P=0.00), duration of breast feeding (P=0.00), using oral contraceptives (P=0.01), and relatives with cancer (P= 0.00). In contrast the results showed no statistically significant differences among the study population related to age at menarche (P=0.46), age at first birth (P=0.37), parents consanguinity (P =0.40), and relatives with cancer (P=1.0). Moreover, within breast cancer patients (n=122) there were statistically significant differences related to age of breast cancer women (P=0.04), age at first birth (P=0.03), and age of onset (P=0.00). But there were no statistically significant differences among the patients related to the age at menarche (P= 0.68), number of pregnancies (P=1.0), duration of breast feeding (P=0.65), and using of contraceptives (P=0.25). Finally, our study results indicated that BRCA1 mutation (185AG and 5382C mutations) incidence (49%) was more than BRCA2 mutations (6174T mutation) incidence (26.5%), and there were patients with both mutations (24.5%). Conclusions: Age is associated with increasing breast cancer risk. Remarkably most risk increase occur during the reproductive years as breast cancer incidence is very low before 22 years. Risk of breast cancer decreased with an increase age at menarche, an increasing parity, a low age at first birth, and breast feeding. The incidence of BRCA1 mutations (185AG and 5382C mutations) was more than BRCA2 mutation ( 6174T mutation).