(ii) Haplotype analyses, based on different combinations of multiple SNPs in Aurora-A, revealed a strong association with breast cancer risk; interestingly, the genotypic distribution of the suggested functional Phe31Ile SNP was not significantly different between breast cancer patients and controls, but the specific haplotype containing the putative at-risk Ile allele was more common in patients.
Analyzing V57I genotypes showed a higher homozygote Val/Val genotype in patients compared with controls (76% vs 68%), whereas the frequency of heterozygous Val/Ile genotype was lower in patients (17%) than controls (30%), yielding a marginal association between breast cancer and Val/Val genotype (P = .048).
As a novel finding, four polymorphisms in STK4 (rs6017452, rs7271519) and AURKA (rs2273535, rs8173) associated with steroid hormone receptor status both in a Swedish population-based cohort of 783 BC cases and in a Polish familial/early onset cohort of 506 BC cases.
For V57I polymorphism, significant decreased breast cancer risk was found among Caucasians (recessive model: OR = 0.76, 95 % CI = 0.61-0.95; AA vs. GG: OR = 0.75, 95 % CI = 0.60-0.94; A vs. G: OR = 0.92, 95 % CI = 0.86-0.98).
High mammographic density, associated with increased breast cancer risk, was encountered more frequently in premenopausal women with the risk genotypes STK15 F31I AA and AT.
However, there was a significant association between tumor stages and F31I genotype (P for trend = .003).This is the first report of F31I and V57I polymorphisms in AURKA gene in breast cancer in Iran.
In particular, a statistically significant interaction was found between BMI and the STK15 Phe(31)Ile polymorphism (P = 0.02) and a positive association with breast cancer risk for the Ile allele was found only among overweight (BMI >/= 25 kg/m(2)) women with adjusted ORs (95% CIs) of 3.3 (1.4-7.7) and 4.1 (1.7-9.8) associated with the Phe/Ile and Ile/Ile genotypes (Pfor trend <0.01), respectively.
In summary, this meta-analysis suggests that STK15 F31I polymorphism is associated with increased breast cancer and ovarian cancer risk among Caucasians, F31I polymorphism is associated with decreased lung cancer risk among Caucasians, and V57I polymorphism is associated with decreased breast cancer risk among Caucasians.
In the Swedish case-control study, associations with BC susceptibility were observed in a dominant model for three MYBL2 promoter polymorphisms (rs619289, P = 0.02; rs826943, P = 0.03 and rs826944, P = 0.02), two AURKA promoter polymorphisms (rs6064389, P = 0.04 and rs16979877, P = 0.02) and one 3'UTR polymorphism in ZNF217 (rs1056948, P = 0.01).
In the Swedish case-control study, associations with BC susceptibility were observed in a dominant model for three MYBL2 promoter polymorphisms (rs619289, P = 0.02; rs826943, P = 0.03 and rs826944, P = 0.02), two AURKA promoter polymorphisms (rs6064389, P = 0.04 and rs16979877, P = 0.02) and one 3'UTR polymorphism in ZNF217 (rs1056948, P = 0.01).
Individually, neither the F31I polymorphism [odds ratio (OR) 1.54; 95% confidence interval (CI) 0.96-2.47, comparing 31I with 31F homozygotes] nor the V57I polymorphism (OR 0.92; 95% CI 0.50-1.71, comparing 57I with 57V homozygotes) was significantly associated with breast cancer risk.
Individually, neither the F31I polymorphism [odds ratio (OR) 1.54; 95% confidence interval (CI) 0.96-2.47, comparing 31I with 31F homozygotes] nor the V57I polymorphism (OR 0.92; 95% CI 0.50-1.71, comparing 57I with 57V homozygotes) was significantly associated with breast cancer risk.
Our results indicate statistical evidence of an association between the STK15 F31I polymorphism and the increased risk of overall cancer in four genetic models: AA vs. TA+TT, AA vs. TT, AA vs. TA, and A vs. T. In a stratified analysis by cancer type, there was an increased risk of breast cancer in four genetic models: AA vs. TA+TT, AA vs. TT, AA vs. TA, and A vs. T, as well as esophageal cancer in two genetic models: AA vs. TA+TT and AA vs. TA.
Single nucleotide polymorphisms (SNPs) in CYP2E1 (rs6413432 and rs3813867), STK15 (rs2273535 and rs1047972) and XRCC1 (rs1799782 and rs25487) have been associated with breast cancer risk in a meta-analysis but any link in Southeast Asia, including Malaysia, remained to be determined.
Stratified analysis by cancer type revealed that the STK rs2273535 polymorphism may contribute to the risk of breast cancer (AA vs. TT: OR=1.21, 95%CI=1.01-1.44, Pheterogeneity=0.002), colorectal cancer (AA vs.
The present meta-analysis suggests that the STK15 F31I polymorphism is a strong predisposing risk factor for breast cancer, but no significant association existed between the STK15 V57I polymorphism and the risk of breast cancer.
The present meta-analysis suggests that the STK15 F31I polymorphism is a strong predisposing risk factor for breast cancer, but no significant association existed between the STK15 V57I polymorphism and the risk of breast cancer.
The results showed that four SNPs in AURKA (data in recessive model, rs2273535: OR = 2.19, 95% CI = 1.03-4.66, p = 0.0422; rs2298016: OR = 0.38, 95% CI = 0.18-0.82, p = 0.0141; rs6024836: OR = 1.54, 95% CI = 1.18-2.00, p = 0.0014; rs10485805: OR = 0.68, 95% CI = 0.47-0.98, p = 0.0380) and one SNP in BRCA1 (rs3737559, dominant model OR = 1.35, 95% CI = 1.11-1.64, p = 0.0030) were associated with breast cancer susceptibility.