بررسی پلی‌مورفیسم تکرار TAAAA در ژن p53 و ارتباط آن با سرطان پستان

نجفی درچه, سمیه; توسلی, منوچهر; همتی, سیمین; صفری, فروزان

بررسی پلی‌مورفیسم تکرار TAAAA در ژن p53 و ارتباط آن با سرطان پستان

نوع مقاله : مقاله های پژوهشی

نویسندگان

¹ دانشجوی کارشناسی ارشد، گروه زیست‌شناسی، دانشکده‌ی علوم، دانشگاه اصفهان، اصفهان، ایران

² دانشیار، گروه زیست‌شناسی، دانشکده‌ی علوم، دانشگاه اصفهان، اصفهان، ایران

³ استادیار، گروه پرتودرمانی، دانشکده‌ی پزشکی، دانشگاه علوم پزشکی اصفهان، اصفهان، ایران

⁴ کارشناس ارشد، گروه زیست‌شناسی، دانشکده‌ی علوم، دانشگاه اصفهان، اصفهان، ایران

چکیده

مقدمه: تغییرات ژنتیک در ژن p53 با تومورزایی، به خصوص تومورهای جامد مانند پستان، کلون و ریه، در ارتباط می‌باشد. جهش‌های ژن p53 بیشترین فراوانی را در سرطان‌های انسان دارد. بر اساس اطلاعات ما، تا زمان انجام این تحقیق، مطالعه‌ای در مورد ارتباط تعداد تکرارهای TAAAA واقع در اینترون 1 ژن p53 و سرطان صورت نگرفته بود. هدف این پژوهش، بررسی پلی‌مورفیسم TAAAA واقع در اینترون 1 ژن p53 در بین مبتلایان به سرطان پستان و افراد شاهد و ارتباط آن با سرطان پستان بود.روش‌ها: در این پژوهش، نمونه‌ی خون 200 زن مبتلا به سرطان پستان و 200 زن شاهد جمع‌آوری و بررسی شد. پس از استخراج DNA ژنومی از خون محیطی و تکثیر توالی مورد نظر، تعداد تکرار و توالی TAAAA با استفاده از الکتروفورز بر روی ژل پلی آکریل آمید و تعیین توالی به دست آمد.یافته‌ها: در این مطالعه، 5 آلل متفاوت از تکرار TAAAA بین 6 تا 10 تکرار و 11 ترکیب آللی (ژنوتیپ) مختلف در بین افراد شاهد و مورد مشاهده شد. بیشترین فراوانی آللی در میان افراد مورد و شاهد مربوط به آلل 8 تکرار بود. خانم‌هایی با ژنوتیپ هتروزیگوت 6 و یا هموزیگوت 7 دارای خطر افزایش یافته‌ای برای ابتلا به سرطان پستان بودند. در این مطالعه، ارتباط معنی‌داری بین این ژنوتیپ‌ها با درجه‌ی پیشرفت بیماری، وضعیت بیان گیرنده‌های استروژن، پروژسترون و Her2 و سن مشاهده نشد.نتیجه‌گیری: مطالعه‌ی ما ارتباط معنی‌داری را بین پلی‌مورفیسم تکرار TAAAA در ژن p53 و خطر ابتلا به سرطان پستان نشان داد. افراد هتروزیگوت 7/6 و 8/6 و نیز هموزیگوت 7/7 خطر افزایش‌‌یافته‌ای برای ابتلا به سرطان پستان دارند.

کلیدواژه‌ها

عنوان مقاله [English]

The Study of TAAAA Polymorphism in p53 Gene and Its Association with Breast Cancer

نویسندگان [English]

Somaye Najafi-Dorche ¹
Manoochehr Tavassoli ²
Simin Hemati ³
Forouzan Safari ⁴

¹ MSc Student, Department of Biology, School of Science, University of Isfahan, Isfahan, Iran

² Associate Professor, Department of Biology, School of Science, University of Isfahan, Isfahan, Iran

³ Assistant Professor, Department of Radiotherapy, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran

⁴ Department of Biology, School of Science, University of Isfahan, Isfahan, Iran

چکیده [English]

Background: Genetic alternation in p53 gene is associated with tumorgenesis, especially in breast, colon and lung tumors. Somatic mutation of the p53 gene is the most common genetic alteration seen in human cancers. To our knowledge, before this research, there was no study on the relationship of TAAAA repeat in the first intron of p53 gene and cancer risk. The purpose of this study was to investigate the polymorphism of TAAAA in the first intron of p53 gene among patients with breast cancer and healthy individuals and its relation to risk of breast cancer.Methods: Peripheral blood samples were collected from 200 women with breast cancer and 200 healthy women. After DNA extraction from peripheral blood samples via salting out method and amplification of desired sequence via polymerase chain reaction (PCR), the number of TAAAA repeats was determined using polyacrylamide gel electrophoresis and direct sequencing.Findings: Five different length of TAAAA repeat in the range of 6-10 and 11 allele combinations (genotypes) were observed among patients and controls. The most frequent allele in both patients and controls was the 8-TAAAA repeat. Women who were homozygous for (TAAAA)7 or heterozygous for (TAAAA)6 were at higher risk of developing breast cancer. The allelic length of p53 polymorphisms had no significant effect on the metastasis, the expression of estrogen receptors, progesterone receptors and ErbB2 (HER2) and age of the onset.Conclusion: Our study shows strong association between the TAAAA repeat polymorphism in p53 gene and risk of breast cancer. On the other hand, women who are homozygous for (TAAAA)7 or heterozygous for (TAAAA)6 are at higher risk of developing breast cancer.

کلیدواژه‌ها [English]

p53
Breast Cancer
TAAAA repeat
Polymorphism

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