Genetic Polymorphisms in CYP1A1, GSTM1, GSTP1, GSTT1, NAT1 and NAT2 and Oral Cavity Cancer Risk among Filipinos

Eva Maria C. Cutiongco-De La Paz,1 Corazon A. Ngelangel,2,3  Alfredo Y. Pontejos,4 Carmencita D. Padilla,Catherine Lynn T. Silao,1 Regie Lyn S. Cortez,4,5 Frances C. Rocamora,1 Arsenio C. Cabungcal,Nathaniel W. Yang,4 Gil M. Vicente6  and Mark U. Javelosa3 for the Philippine Cancer Genetics Study Group

1Institute of Human Genetics, National Institutes of Health, University of the Philippines Manila
2Institute of Clinical Epidemiology, National Institutes of Health, University of the Philippines Manila
3Section of Medical Oncology, Department of Medicine, College of Medicine and
Philippine General Hospital, University of the Philippines Manila
4Department of Otorhinolaryngology, College of Medicine and
Philippine General Hospital, University of the Philippines Manila
5Philippine National Ear Institute, National Institutes of Health, University of the Philippines Manila
6Department of Otorhinolaryngology, Jose R. Reyes Memorial Medical Center, Rizal Avenue, Sta. Cruz, Manila

Polymorphisms in metabolic genes have been shown to modulate susceptibility to oral cavity cancer. Cases (n=176) and controls (n=317) from the Filipino population were genotyped for selected polymorphisms in CYP1A1, GSTM1, GSTP1, GSTT1, NAT1 and NAT2. Medical and diet histories, occupational exposure and demographic data were also collected for all subjects. The CYP1A1m1/m1 genotype is protective against oral cancer, while being homozygous for the GSTP1 c.313G genotype and heterozygous for the NAT1*10 homozygotes and non-homozygotes for the CYP1A1 m1 allele. The risk from heterozygosity for the NAT1*10 allele was limited to subjects who were not homozygous for the GSTP1 c.313G genotype remained a significant oral cancer risk modifier, together with environmental variables, the homozygous GSTP1 c.313G genotype remained a significant oral cancer risk modifier, together with environmental risk factors, such as smoking, passive smoking, inverted smoking and tobacco chewing, and environmental protective factors, i.e. moderate consumption of fish sauce (patis) and shrimp paste (bagoong). The GSTP1 c.313G polymorphism increases susceptibility for oral cavity cancer in the Filipino population.

Key Words: Filipinos, genetic polymorphisms, metabolic enzyme, oral cavity cancer, risk factor, susceptibility