Xuechen Wang

Variant genotypes of CDKN1A and CDKN1B are associated with an increased risk of breast cancer in Chinese women

p21Cip1 and p27Kip1 are cyclin‐dependent kinase inhibitors, which can arrest cell proliferation and serve as tumor suppressors. Reduced protein expression of p21Cip1 and p27Kip1 was frequently observed in a subset of cancers, including breast cancer. In this study, we hypothesized that genetic variants in CDKN1A (encode for p21Cip1) and CDKN1B (encode for p27Kip1) may modulate the risk of breast cancer. To test this hypothesis, we evaluated the associations of the polymorphisms of Ser31Arg and C+20T in CDKN1A and C−79T and Gly109Val in CDKN1B, as well as their combinations, with breast cancer risk in a case‐control study of 368 breast cancer cases and 467 cancer‐free controls in a Chinese population. We found that a significantly increased risk of breast cancer was associated with the variant genotypes of CDKN1B C−79T [adjusted OR = 1.43 (95% CI = 1.03−1.98) for −79TC/TT], compared with the −79CC genotype, but no associations were observed for other variant genotypes. However, the combined variant genotypes of the 4 loci were associated with a significantly increased breast cancer risk (adjusted OR = 1.49, 95% CI = 1.11−2.01 among subjects carrying 3 or more variant alleles), especially among premenopausal women (adjusted OR= 2.30, 95% CI = 1.45−3.66). Furthermore, in premenopausal women, this significant association remained unchanged, after including other individual risk factors in the multivariate logistic regression model, suggesting an independent role of CDKN1A and CDKN1B variants in breast cancer risk. Although the exact biological mechanism remains to be explored, our findings suggest possible involvement of CDKN1A and CDKN1B variants in the etiology of breast cancer. Further large and functional studies are needed to confirm our findings.

A tandem repeat of human telomerase reverse transcriptase (hTERT) and risk of breast cancer development and metastasis in Chinese women

Telomerase reactivation, which prevents telomere shortening and maintains cell viability, is crucial for the continued growth or progression of cancer cells. A minisatellite tandem repeat, MNS16A, located in the downstream of the human telomerase reverse transcriptase (hTERT) gene was recently identified and reported to have an effect on hTERT expression and telomerase activity. The aim of this study was to test the hypothesis that the MNS16A variant is associated with risk of breast cancer development and metastasis. We genotyped MNS16A variant in hTERT in a case-control study of 1029 histologically confirmed breast cancer patients and 1107 cancer-free controls in Chinese women. The variant genotypes (302/271, 302/243 and 243/243) of MNS16A were associated with a significantly increased risk of breast cancer [adjusted odds ratio (OR) = 1.50, 95% confidence interval (CI) = 1.15-1.96], compared with the wild-type 302/302 genotype. In stratified analyses, we found that the 302/271 genotype was associated with a significantly increased risk of axillary lymph nodes metastasis (adjusted OR = 2.13, 95% CI = 1.05-4.33) compared with wild-type 302/302 genotype. These findings indicate that the MNS16A variant in the hTERT gene may contribute to the risk of breast cancer development and metastasis in Chinese women.

Functional variants in the promoter of interleukin-1β are associated with an increased risk of breast cancer: A case-control analysis in a Chinese population

Interleukin 1β (IL‐1β) is a multifunctional cytokine that upregulates the inflammatory response, and participates in carcinogenesis, malignant transformation, tumor growth, invasion and metastasis. Two potentially functional polymorphisms (T‐31C and C‐511T) in the IL‐1β gene promoter were suggested to be correlated with alteration of IL‐1β expression and therefore may be associated with cancer risk. To test the hypothesis that these 2 polymorphisms are associated with risk of breast cancer, we performed a case‐control study of 365 breast cancer cases, 270 patients with benign breast diseases (BBD) and 631 cancer‐free controls in a Chinese population. Multivariate logistic regression analyses revealed that increased risk of breast cancer was associated with IL‐1β‐31C variant genotypes [adjusted odds ratio (OR) = 1.28 and 95% confidence interval (CI) = 0.91–1.80 for ‐31CT and 1.72 (95% CI = 1.16‐2.54) for ‐31CC], compared with the ‐31TT genotype. Similarly, IL‐1β‐511T variant genotypes were also associated with increased risk of breast cancer (adjusted OR = 1.20, 95% CI = 0.86–1.67 for ‐511CT and adjusted OR = 1.74, 95% CI = 1.18–2.56 for ‐511TT), compared with the ‐511CC genotype. Furthermore, cancer risks associated with IL‐1βT‐31C variant genotypes were more evident in older women, postmenopausal women and individuals with a later menarche age. Interestingly, although we did not find significant associations of these 2 variants with cancer risk when compared with the BBD patients, a 1.27‐fold (95% CI = 1.01–1.60) increased risk was observed with the ‐31C‐511T common haplotype. These findings indicate that these 2 IL‐1β promoter variants may contribute to risk of developing breast cancer in the Chinese population.