XPD Lys751Gln increases the risk of breast cancer.

Breast cancer incidence has been on the increase in south Indian women. Polymorphisms in DNA repair genes modify an individual's risk to cancer. XPD (Xeroderma pigmentosum D), a DNA helicase gene involved in nucleotide excision repair and transcription coupled repair, may affect an individual's DNA repair capacity, particularly that of bulky adducts. This case-control study (250 breast cancer cases and 500 healthy controls) aimed to investigate the role of the XPD Lys751Gln polymorphism as a risk factor in the development of breast cancer. Genotyping was performed using the Taq Man allelic discrimination assay. Immunohisto-chemistry was used to quantitate the level of polycyclic aromatic hydrocarbon (PAH) adducts in biopsy samples obtained from the breast cancer patients. Results showed that the XPD Gln/Gln genotype was significantly associated with an increased risk of breast cancer (OR, 1.75; 95% CI 1.02-2.80), particularly in premenopausal female patients (OR, 2.6; 95% CI 1.33-4.79). PAH adduct levels were significantly higher in the cases with breast cancer as compared to the normal breast tissue. This study reveals that XPD may play a role in increasing breast cancer risk particularly in premenopausal females.