Novel Genetic Susceptibility Markers for Breast Cancer in Iraqi Women: First Evidence of CYP3A4*1B Protective Effects and GSTP1/MTHFR Risk Associations.

[BACKGROUND] This is the first study looking at breast cancer risk using the polymorphisms CYP3A4*1B, GSTP1 Ile105Val, MTHFR C677T, and COMT Val158Met for breast cancer predisposed Iraqi population with specific environmental carcinogenic exposures.

[METHODS] Aged matched healthy controls were 610 individuals of Iraqi origin alongside 414 histologically confirmed breast cancer patients forming a case-control study cohort. CDNA was obtained from peripheral blood samples, which underwent genotyping via tetra-primer ARMS-PCR. Statistical evaluation was performed based on several genetic models with odds ratios (OR) and 95% confidence intervals (CI) calculated by logistic regression.

[RESULTS] For 3 polymorphisms, crucial associations were found and these include CYP3A4*1B which showed a protective effect against breast cancer (OR = 0.72, 95% CI, 0.54-0.96, P = .027), the effect being strong in women less than 50 years old. Increased cancer risk was associated with GSTP1 Ile105Val (OR = 1.68, 95% CI, 1.23-2.31, P = .001) especially in older females and those with elevated BMI. The same risk was also conferred by MTHFR C677T (OR = 1.45; 95% CI, 1.12-1.89, P = .005). No significant association for COMT Val158Met was observed (P = .156). All polymorphisms among controls were in Hardy-Weinberg equilibrium.

[CONCLUSIONS] The study presented the taw evidence of both CYP3A4*1B and GSTP1 Ile105Val along with MTHFR C677T polymorphisms associating them to breast cancer susceptibility in Iraqi population which reflects these specific genetic risks and reinforces middle eastern populations towards precision medicine frameworks concerning breast cancer treatment and intervention strategies.