Sains Malaysiana 47(1)(2018): 141–148

http://dx.doi.org/10.17576/jsm-2018-4701-17

STK15 Phe31Ile and Val57Ile Polymorphisms Increase the Risk of Gastrointestinal Cancer

(Polimorfisme STK15 Phe31Ile dan Val57Ile Meningkatkan Risiko terhadap Kanser Gastrousus)

TIANXIN LAI¹, ERIC TZYY JIANN CHONG¹, JITT AUN CHUAH², KEK HENG CHUA³ & PING-CHIN LEE^1*

¹Biotechnology Programme, Faculty of Science and Natural Resources, Universiti Malaysia Sabah, Jalan UMS, 88400 Kota Kinabalu, Sabah Negeri di Bawah Bayu, Malaysia

²Surgery Department, Queen Elizabeth Hospital, Jalan Penampang, 88200 Kota Kinabalu, Sabah Negeri di Bawah Bayu, Malaysia

³Department of Biomedical Science, Faculty of Medicine Building, University of Malaya, 50603 Kuala Lumpur, Federal Territory, Malaysia

Diserahkan: 15 Januari 2016/Diterima: 3 Jun 2017

ABSTRACT

STK15 is a serine/threonine kinase that regulates chromosomal segregation during mitosis. Single nucleotide polymorphisms (SNPs) in this gene, Phe31Ile (rs2273535) and Val57Ile (rs1047972), are inconsistently associated with gastrointestinal cancer (GIC) across different populations. However, this association is unclear in Malaysian population. Therefore, this study investigated the association of STK15 Phe31Ile and Val57Ile polymorphisms to GIC risk in Malaysia. Genomic DNA was extracted from 185 GIC patients and 1110 healthy controls and was subjected to polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) analysis. SNPs were further confirmed using sequencing. We found that the 31Phe allele and 31Phe/Phe genotype in the Phe31Ile SNP significantly increased GIC risk in Malaysian population, particularly in gastric cancer (p<0.017). The combined analysis for both SNPs also increased the risk of GIC in this study. Etiological factors such as age, gender and ethnicity were not associated with GIC in the population. This is the first study to report the association of STK15 Phe31Ile and Val57Ile SNPs with an increased risk of GIC in Malaysians; the 31Phe allele is exclusively associated with the risk of gastric cancer. In addition, GIC incidences among Malaysians have significantly shifted to a younger age (<50 years).

Keywords: Gastrointestinal cancer; Malaysian population; STK15 polymorphisms

ABSTRAK

STK15 adalah kinase serin/treonina yang mengawal perpisahan kromosom semasa mitosis. Polimorfisme nukleotida tunggal (SNPs) pada gen ini, Phe31Ile (rs2273535) dan Val57Ile (rs1047972) adalah dikaitkan dengan kanser gastrousus (GIC) secara tidak tekal dalam populasi yang berbeza. Walau bagaimanapun, perkaitan tersebut adalah tidak jelas di dalam populasi di Malaysia. Oleh itu, penyelidikan ini mengkaji perkaitan bagi polimorfisme STK15 Phe31Ile dan Val57Ile terhadap risiko GIC di Malaysia. DNA genom diekstrak daripada 185 pesakit GIC dan 1110 kawalan yang sihat. Seterusnya, analisis tindak balas berantai polimerase pemotongan panjang cebisan (PCR-RFLP) dijalankan dan SNP turut disahkan dengan menggunakan teknik penjujukan DNA. Kami mendapati bahawa alel 31Phe dan genotip 31Phe/Phe dalam SNP Phe31Ile meningkatkan risiko terhadap GIC dalam populasi di Malaysia secara signifikan, terutamanya dalam kanser gastrik (p<0.017). Analisis gabungan bagi kedua-dua SNP juga meningkatkan risiko terhadap GIC dalam kajian ini. Faktor etiologi seperti umur, jantina dan etnik adalah tidak berkait dengan GIC dalam populasi ini. Kajian ini merupakan kajian pertama yang melaporkan tentang perkaitan antara SNP STK15 Phe31Ile dan Val57Ile dengan peningkatan risiko terhadap GIC di Malaysia; terutamanya alel 31Phe yang dikaitkan dengan risiko kanser gastrik. Selain itu, kejadian GIC dalam kalangan rakyat Malaysia telah beralih secara signifikan kepada usia yang lebih muda (<50 tahun).

Kata kunci: Kanser gastrousus; polimorfisme STK15; populasi Malaysia

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*Pengarang untuk surat-menyurat; email: leepc@ums.edu.my