PD-1 rs2227982 Polymorphism Is Associated With the Decreased Risk of Breast Cancer in Northwest Chinese Women

Abstract

Programmed death-1 (PD-1) is crucial in cancer and is well characterized as a negative T-cell regulator that functions by delivering inhibitory signals. We aimed to evaluate the relationship between PD-1 polymorphisms (rs10204525, rs2227982, and rs7421861) and breast cancer risk.We selected 560 breast cancer patients and 583 age-, sex-, and ethnicity-matched healthy controls from Northwest China. The PD-1 polymorphisms were genotyped by using Sequenom MassARRAY. Associations were estimated with odds ratios (ORs) and 95% confidence intervals (95% CIs).For the rs10204525 and rs7421861 polymorphisms, no differences in breast cancer risk were found in any of the genetic models. For the rs2227982 polymorphism, the variant genotypes were significantly associated with decreased breast cancer risk (CT vs CC: OR = 0.68, 95% CI = 0.52–0.91; CT + TT vs CC: OR = 0.69, 95% CI = 0.53–0.90). In analyses stratified by age, the decreased risk was observed among the younger subjects (OR = 0.68, 95% CI = 0.47–0.97). We found that the decreased risk observed for the variant genotypes of rs2227982 was associated with the Her-2 status (CT vs CC: OR = 0.55, 95% CI = 0.37–0.84; CT + TT vs CC: OR = 0.56, 95% CI = 0.38–0.82). The haplotype analysis showed that the Ars10204525 Trs2227982 Crs7421861 haplotype was associated with a significantly decreased risk of breast cancer (OR = 0.50, 95% CI = 0.34–0.75).Our findings support an association between the PD-1 rs2227982 polymorphism and decreased breast cancer risk, especially in Her-2 positive breast cancer patients in the Chinese population.

Correlation between IL‐7R gene variants and breast cancer susceptibility in Chinese Han women

“…Genetic variations, including single nucleotide polymorphism, were closely related to the occurrence of breast cancer. Genome-wide association studies (GWAS) have detected many SNPs were related to breast cancer susceptibility in tumor-related genes such as PD-1, FGFR2, ESR1, PTEN, and MAP3K1 [17][18][19]. The effect of IL-7R SNPs on breast cancer susceptibility in Chinese Han population is not clear at present.…”

Immunoterapia z użyciem przeciwciał monoklonalnych ukierunkowanych na szlak PD-1/PD-L1 w chorobach nowotworowych

“…Dodatkowo, dowiedziono brak związku między ryzykiem zachorowania na raka a PD1.9 (rs2227982) lub PD1 rs7421861 SNP w modelach genetycznych [96]. Badania uzupełniające wykazały związek między polimorfizmem PD1 rs2227982 i obniżeniem ryzyka wystąpienia raka piersi, szczególnie u chorych z obecnością genu HER-2 [96,101]. Zaobserwowano również, że obecność polimorfizmu rs2227982 podwyższa ryzyko wystąpienia gruczolakoraka żołądka [100].…”

LRRC3B polymorphisms contributed to breast cancer susceptibility in Chinese Han Population

“…Age, serum hormone levels, family history and environmental factors have been identi ed as potential contributors BC susceptibility [4]. Moreover, genetic factors were the major drivers in the genesis of BC [5][6][7].…”