Genetic Polymorphisms in NAT1, NAT2, GSTM1, GSTP1 and GSTT1 and Susceptibility to Colorectal Cancer among Filipinos

Eva Maria C. Cutiongco-de la Paz,1,2 Corazon A. Ngelangel,3
Virgilio P. Bañez,4 Francisco T. Roxas,5 Catherine Lynn T. Silao,1
Jose B. Nevado Jr.,1 Alberto B. Roxas,5   Oliver G. Florendo,4
Ma. Cecilia M. Sison,4 Orlino Bisquera, Jr.,5 Luminardo M. Ramos,5
Elizabeth A. Nuqui,6 Arnold Joseph M. Fernandez,6 Maria Constancia O. Carrillo,7
Beatriz J. Tiangco,1,8 Aileen D. Wang,9 Rosalyn H. Sebastian,9
Richmond B. Ceniza,9 Leander Linus Philip P. Simpao,9 Lakan U. Beratio,9
Eleanor A. Dominguez,9  Albert B. Albay Jr.,9 Alfredo Y. Pontejos Jr.,10
Nathaniel W. Yang,10 Arsenio A. Cabungcal,10 Rey A. Desales,11
Nelia S. Tan-Liu,11 Sullian S. Naval,11 Roberto M. Montevirgen,11
Catalina de Siena E. Gonda-Dimayacyac,11 Pedrito Y. Tagayuna,11
John A. Coloma,12 Gil M. Vicente,12 Higinio T. Mappala,12
Alex C. Tapia,12 Emmanuel F. Montana Jr.,12 Jonathan M. Asprer,12
Reynaldo O. Joson,13 Sergio P. Paguio,13 Tristan T. Chipongian,14
Joselito F. David,14 Florentino C. Doble,14 Maria Noemi G. Pato,14
Benito B. Bionat Jr.,15 Hans Francis D. Ferraris,15 Adonis A. Guancia,15
Eriberto R. Layda,15 Andrew D. Dimacali,16 Conrado C. Cajucom,16
Richard C. Tia,16 Mark U. Javelosa,3 Regie Lyn P. Santos-Cortez,17,18
Frances Maureen C. Rocamora,1 Roemel Jeusep Bueno1 and
Carmencita D. Padilla1,2,19

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 Gastroenterology, Department of Medicine, College of Medicine and
Philippine General Hospital, University of the Philippines Manila
5Department of Surgery, College of Medicine and
Philippine General Hospital, University of the Philippines Manila
6Department of Pathology, College of Medicine, University of the Philippines Manila
7College of Arts and Sciences, University of the Philippines Manila
8National Kidney and Transplant Institute
9Section of Pulmonary Medicine, Department of Medicine, College of Medicine and
Philippine General Hospital, University of the Philippines Manila
10Department of Otorhinolaryngology, College of Medicine and
Philippine General Hospital, University of the Philippines Manila
11Lung Center of the Philippines
12Jose R. Reyes Memorial Medical Center
13Ospital ng Maynila
14East Avenue Medical Center
15Corazon Locsin Montelibano Memorial Regional Hospital
16Medical Center Manila
17University of Colorado School of Medicine, Colorado, USA
18Philippine National Ear Institute, National Institutes of Health,
University of the Philippines Manila
19Department of Pediatrics, College of Medicine and
Philippine General Hospital, University of the Philippines Manila

Objectives. Polymorphisms in metabolic genes which alter rates of bioactivation and detoxification have been shown to modulate susceptibility to colorectal cancer. This study sought to evaluate the colorectal cancer risk from environmental factors and to do polymorphism studies on genes that code for Phase I and II xenobiotic metabolic enzymes among Filipino colorectal cancer patients and matched controls.

Methods. A total of 224 colorectal cancer cases and 276 controls from the Filipino population were genotyped for selected polymorphisms in GSTM1, GSTP1, GSTT1, NAT1 and NAT2. Medical and diet histories, occupational exposure and demographic data were also collected for all subject participants.

Results. Univariate logistic regression of non-genetic factors identified exposure to UV (sunlight) (OR 1.99, 95% CI: 1.16-3.39) and wood dust (OR 2.66, 95% CI: 1.21-5.83) and moldy food exposure (OR 1.61, 95% CI:1.11-2.35) as risk factors; while the NAT2*6B allele (recessive model OR 1.51, 95% CI :1.06-2.16; dominant model OR 1.87, 95% CI: 1.05-3.33) and homozygous genotype (OR 2.19, 95% CI: 1.19-4.03) were found to be significant among the genetic factors. After multivariate logistic regression of both environmental and genetic factors, only UV radiation exposure (OR 2.08, 95% CI: 1.21-3.58) and wood dust exposure (OR 2.08, 95% CI: 0.95-5.30) remained to be significantly associated with increasing colorectal cancer risk in the study population.

Conclusion. This study demonstrated that UV sunlight and wood dust exposure play a greater role in influencing colorectal cancer susceptibility than genotype status from genetic polymorphisms of the GST and the NAT` genes.

Key Words: colorectal cancer, genetic polymorphisms, xenobiotic metabolizing enzymes, Filipino, susceptibility