Association of CYP1A1 polymorphisms with breast cancer in North Indian women.
Cytochrome P-450 (CYP) 1A1 is a candidate gene for low penetrance breast cancer (BC) susceptibility. Evidences demonstrate that ethnic differences in BC incidence may be partly due to genetic factors, including polymorphisms in the genes. In the present case control study four CYP1A1 gene polymorphisms, m1 (T6235C), m2 (A4889G), m3 (T5639C), and m4 (C4887A) were studied for their association with BC conjointly with the known risk factors such as age, menopausal status, diet, and life style. Polymorphisms of CYP1A1 gene were detected by PCR-RFLP method. The homozygous mutant (G/G) of m2 polymorphism was significantly associated with BC. Consequently, association of both m2 heterozygous mutant genotype (A/G) and combined group [homozygous (G/G) plus heterozygous (A/G) mutant genotype] showed association with postmenopausal women. Incidences of BC were also found to be independent of clinicopathological factors except heterozygous mutant genotype (A/G) m2 showed association with dietary factors and high grade tumors while homozygous mutant (G/G) m2 showed association with ER/PR-positive BC cases. Wild-type m3 was observed in all the subjects in cases as well as in controls. No significant association was observed between m1 and m3 polymorphisms and BC risk in all the subjects as well as when stratified into pre- and postmenopausal subjects. This indicates that out of ml and m2 polymorphisms that have been reported in Asians, only m2 is associated with North Indians.
Singh
Neetu
N
Genotoxicity Laboratory, Toxicology Division, Central Drug Research Institute, Lucknow 226 001, Uttar Pradesh, India. neetuaashi@yahoo.com
Mitra
Amit Kumar
AK
Garg
Vivek Kumar
VK
Agarwal
Amit
A
Sharma
Mandira
M
Chaturvedi
Rashmi
R
Rath
Srikanta Kumar
SK
D000328:Adult; D000368:Aged; D001943:Breast Neoplasms / Q000201:enzymology / Q000235:genetics*; D019363:Cytochrome P-450 CYP1A1 / Q000235:genetics*; D004032:Diet; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D006579:Heterozygote; D006720:Homozygote; D006801:Humans; D007194:India; D008875:Middle Aged; D009154:Mutation; D012150:Polymorphism, Restriction Fragment Length; D020641:Polymorphism, Single Nucleotide; D017698:Postmenopause / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012307:Risk Factors
D019363:Cytochrome P-450 CYP1A1