The Prevalence of CYP2D6 Gene Polymorphisms among Filipinos and their use as Biomarkers for Lung Cancer Risk

Eva Maria Cutiongco-de la Paz,1,2 Corazon A. Ngelangel,3 Aileen David-Wang,4
Jose B. Nevado Jr.,1 Catherine Lynn T. Silao,1 Rosalyn Hernandez-Sebastian,4
Richmond B. Ceniza,4 Leander Linus Philip P. Simpao,4 Lakan U. Beratio,4
Eleanor A. Dominguez,4 Albert B. Albay Jr.,4 Rey A. Desales,5 Nelia Tan-Liu,5
Sullian Sy-Naval,5 Roberto M. Montevirgen,5 Catalina de Siena Gonda-Dimayacyac,5
Pedrito Y. Tagayuna,5 Elizabeth A. Nuqui,6 Arnold Joseph M. Fernandez,6
Andrew D. Dimacali,7 Maria Constancia Obrerro-Carrillo,8 Virgilio P. Banez,9
Oliver G. Florendo,9 Ma. Cecilia M. Sison,9 Francisco T. Roxas,10
Alberto B. Roxas,10 Orlino C. Bisquera Jr.,10 Luminardo M. Ramos,10
John A. Coloma,11 Higinio T. Mappala,11 Alex C. Tapia,11 Emmanuel F. Montana Jr.,11
Jonathan M. Asprer,11 Reynaldo O. Joson,12 Sergio P. Paguio,12
Conrado C. Cajucom,7 Richard C. Tia,7 Tristan Chipongian,13 Joselito F. David,13
Florentino C. Doble,13 Maria Noemi G. Pato,13 Benito B. Bionat Jr.,14
Hans Francis D. Ferraris,14 Adonis A. Guancia,14 Eriberto R. Layda,14
Frances Maureen C. Rocamora,1 Roemel Jeusep Bueno1 and Carmencita D. Padilla1,2,15

1Institute of Human Genetics, National Institutes of Health,
University of the Philippines Manila
2Philippine Genome Center
3Institute of Clinical Epidemiology, National Institutes of Health,
University of the Philippines Manila
4Section of Pulmonary Medicine, Department of Medicine, College of Medicine and
Philippine General Hospital, University of the Philippines Manila
5Lung Center of the Philippines
6Department of Pathology, College of Medicine,
University of the Philippines Manila
7Medical Center Manila
8College of Arts and Sciences, University of the Philippines Manila
9Section of Gastroenterology, Department of Medicine, College of Medicine and
Philippine General Hospital, University of the Philippines Manila
10Department of Surgery, College of Medicine and
Philippine General Hospital, University of the Philippines Manila
11Jose R. Reyes Memorial Medical Center
12Ospital ng Maynila
13East Avenue Medical Center
14Corazon Locsin Montelibano Memorial Regional Hospital
15Department of Pediatrics, College of Medicine and
Philippine General Hospital, University of the Philippines Manila

Objectives. The highly polymorphic nature of the CYP2D6 gene and its central role in the metabolism of commonly used drugs make it an ideal candidate for pharmacogenetic screening. This study aims to determine the prevalence of CYP2D6 polymorphisms among Filipinos and their association to lung cancer.

Method. Forty seven single nucleotide polymorphisms (SNPs) of the CYP2D6 gene were genotyped from DNA samples of 115 cases with lung cancer and age- and sex-matched 115 controls.

Results. Results show that 18 out of 47 polymorphisms have significant genotypic variability (>1% for at least 2 genotypes). No variant is associated with lung cancer. However, rs1135840, rs16947 and rs28360521, were found to be highly variable among Filipinos.

Conclusion. This study demonstrated that CYP2D6 polymorphisms are present among Filipinos, which, although not found to be associated with lung cancer, can be useful biomarkers for future pharmacogenetic studies. The SNP rs16947 is found to be associated with cancer and timolol-induced bradycardia; the SNP rs1135840, on the other hand, is only shown to be linked with cancer. The genetic variant rs28360521 is known to be associated with low-dose aspirin-induced lower gastrointestinal bleeding.

Key Words: Filipino, pharmacogenetics, CYP2D6, lung cancer, biomarker, SNP