UICC World Cancer Congress 2006

Methods:Genomic DNA was extracted from 204 breast cancer patients, including 122 (59.9%) early-onset (<40yrs) and forty-six (22.5%) cases with family history of breast/ovarian cancer. Mutations were detected by Heteroduplex/ SSCP/PCR-RFLP method followed by sequencing. Results:. The mutations in BRCA1/2 genes were noticed in 11.3%(23/204) patients. A sequence alteration was observed in 15 out of 98 early-onset cases without family history(15.3%) compared to 8.6% (4/46) among cases with a family history. Screening for mutations in E-cadherin gene, a candidate tumor suppressor gene, showed two novel missense mutations in two early onset breast cancers without any family history, one presenting as invasive lobular and the other as high-grade invasive ductal case. Both these cases were also harboring a BRCA2 splice site mutations.

The CYP17 gene is involved in steroid biosynthesis pathway. A single T>C polymorphism in the 5' promoter region of the gene is reported to be associated with increased risk of breast cancer .Screening has shown that 85.9% cases were either heterozygous or homozygous for the A2 variant of CYP17 compared with 48.9% in control population. A statistically significant increased risk in carriers of at least one A2 allele was found in young patients [p <0.001] compared with patients having late onset cancer condition. Results show accumulation of mutations in both high and low penetrance genes in early onset cases without having any family history.