MICA-129Met/Val Polymorphism Is Associated with Early-Onset Breast Cancer Risk

ABSTRACT

The major histocompatibility complex class I-related chain A (MICA), expressed on cell surface, plays an important role in the elimination of both virus-infected cells and tumor through the activation of the natural killer (NK) receptor NKG2D. A polymorphic change from methionine (Met) to valine (Val) at amino acid position 129 categorizes MICA alleles into strong and weak binders for the NKG2D receptor and has been found in a variety of immune-related disorders. In this study, we investigated the potential interaction between genetic polymorphism of MICA and the development of breast cancer. We recruited 192 unrelated Tunisian women affected by breast cancer and 205 controls age-matched women, all genotyped for MICA-129 Met/Val (rs 1051792). A significant association was found between the Val allele and Val/Val genotype and the risk of breast cancer (p = 0.002, OR = 1.64, 95% CI = [1.17–2.27]; p = 0.002, OR = 1.88, 95% CI = [1.24–2.87], respectively). After stratification with clinical-pathology parameters, we found that 71% of women aged lower than 40 years had a Val/Val genotype versus 49% (p = 0.014). About 72% of these patients having a family history of cancers had a Val/Val genotype (p = 0.04). These results suggest that tumor escape mechanism because of failure in order to activate NK cells by MICA-129 Val allele may play a role in individual susceptibility for breast cancer development in Tunisian women.

KEYWORDS:

• Breast cancer
• early onset
• MICA
• polymorphism
• risk

Declaration of interest

The authors declare no conflict of interest.

Ethics

The authorization was given by the Ethics Review Board of the Salah Azaiez Institute.

Funding

This work was supported by the institutional funding to INSERM UMRS 1160 team and Assistance Public des Hopitaux de Paris (AP-HP) and by the French-Tunisian (Tamouza-Guemira) bilateral co-operation. The study was funded by departmental resources.

Additional information

Funding

This work was supported by the institutional funding to INSERM UMRS 1160 team and Assistance Public des Hopitaux de Paris (AP-HP) and by the French-Tunisian (Tamouza-Guemira) bilateral co-operation. The study was funded by departmental resources.