title: Role of ethnic variations in TNF-α and TNF-β polymorphisms and risk of breast cancer in India.
abstract: TNF-α and -β, the multi-functional pro-inflammatory cytokines, are known to play important roles in both tumor progression and destruction based on their concentrations. Growth factors and various stimuli such as cytokines regulate proliferation of the breast epithelial cells. Therefore, the polymorphisms in the genes encoding these signaling molecules could affect the risk of breast cancer. We have investigated selected genetic polymorphisms in TNF-α promoter (rs1800629, -308 G>A and rs361525, -238 G>A) and TNF-β intron 1 (rs909253, +252 A>G) in ethnically two different case-control groups from India. The study included 200 cases and 200 controls from an Indo-European (North Indian) group, and 265 cases and 237 controls from a Dravidian (South Indian) group. Genotyping of a total of 902 individuals was done by direct DNA sequencing. None of the polymorphisms showed significant association with breast cancer in the Indo-European group; however, all the three polymorphisms showed strong association with breast cancer in the Dravidian group. Further, sub-group analysis in the Indo-European group showed no significant difference between pre-menopausal cases and controls or between post-menopausal cases and controls at any of the loci analyzed. However, all the polymorphisms in the Dravidian group were significantly associated with pre-menopausal but not with post-menopausal breast cancer. In conclusion, TNF-α and -β polymorphisms are strongly associated with breast cancer in the Dravidian but not in the Indo-European group.
authors.affiliation: Endocrinology Division, Central Drug Research Institute (CSIR), Lucknow 226001, UP, India.
authors.forename: Singh
authors.initials: S
authors.lastname: Pooja
authors.forename: Amirtharaj
authors.initials: A
authors.lastname: Francis
authors.forename: Hemant Kumar
authors.initials: HK
authors.lastname: Bid
authors.forename: Sandeep
authors.initials: S
authors.lastname: Kumar
authors.forename: Singh
authors.initials: S
authors.lastname: Rajender
authors.forename: K
authors.initials: K
authors.lastname: Ramalingam
authors.forename: Kumarasamy
authors.initials: K
authors.lastname: Thangaraj
authors.forename: Rituraj
authors.initials: R
authors.lastname: Konwar
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001940:Breast / Q000378:metabolism; D001943:Breast Neoplasms / Q000208:ethnology* / Q000235:genetics*; D016022:Case-Control Studies; D005006:Ethnicity; D005260:Female; D014644:Genetic Variation; D005838:Genotype; D006801:Humans; D007194:India; D008233:Lymphotoxin-alpha / Q000235:genetics*; D008593:Menopause; D008875:Middle Aged; D011110:Polymorphism, Genetic; D012306:Risk; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics*
chemical_list: D008233:Lymphotoxin-alpha; D014409:Tumor Necrosis Factor-alpha