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This study used the alkaline Comet assay to evaluate whether basal or H2O2-induced DNA damage is associated with prostate cancer (CaP) risk. Using lymphocyte samples from 158 CaP cases and 128 controls, collected in an ongoing case–control study, our results showed that basal DNA damage did not differ between cases and controls. However, the H2O2-induced DNA damage level was significantly higher in incident cases (mean ± SD; 6.61 ± 4.43, n = 102) than controls (5.30 ± 3.60, n = 128) or prevalent cases (4.47 ± 3.19; n = 56). Incident cases with a positive smoking history had significantly higher H2O2-induced DNA damage than never-smokers (7.57 ± 4.82 versus 4.52 ± 2.40; P < 0.001). Above-median H2O2-induced DNA damage was associated with a 1.61-fold increase in CaP risk [95% confidence interval (CI) = 0.92–2.81], after adjustment for age, race, benign prostatic hyperplasia (BPH), smoking history and family history (FH). Using the lowest quartile of H2O2-induced DNA damage as the referent group, the adjusted ORs for the 25th, 50th and 75th quartiles were 0.90 (95% CI = 0.39–2.05), 1.06 (95% CI = 0.48–2.35) and 2.05 (95% CI = 0.96–4.37), respectively (P = 0.046, test for linear trend). The association between CaP and DNA damage was modified by age, smoking history, family history and body mass index. Our results suggest that DNA damage may be associated with CaP risk. However, larger case–control and follow-up studies are warranted to further evaluate the potential application of the alkaline Comet assay in CaP risk assessment and prevention. [ABSTRACT FROM AUTHOR]

Genetic variations in DNA repair may impact repair functions, DNA damage and breast cancer risk. Using data/samples collected from the first 752 Caucasians and 141 African-Americans in an ongoing case–control study, we examined the association between breast cancer risk and 18 non-synonymous single-nucleotide polymorphisms (nsSNPs) in four DNA repair pathways—(i) base excision repair: ADPRT V762A, APE1 D148E, XRCC1 R194W/R280H/R399Q and POLD1 R119H; (ii) nucleotide excision repair: ERCC2 D312N/K751Q, ERCC4 R415Q, ERCC5 D1104H and XPC A499V/K939Q; (iii) mismatch repair: MLH1 I219V, MSH3 R940Q/T1036A and MSH6 G39E and (iv) double-strand break repair: NBS1 E185Q and XRCC3 T241M. In Caucasians, breast cancer risk was significantly associated with ADPRT 762VV [odds ratio (OR) = 1.45; 95% confidence interval (CI) = 1.03, 2.03], APE1 148DD (OR = 1.44; 95% CI = 1.03, 2.00), MLH1 219II/IV (OR = 1.87; 95% CI = 1.11, 3.16) and ERCC4 415QQ (OR = 8.64; 95% CI = 1.04, 72.02) genotypes. With a limited sample size, we did not observe any significant association in African-Americans. However, there were significant trends in breast cancer risk with increasing numbers of risk genotypes for ADPRT 762VV, APE1 148DD, ERCC4 415RQ/QQ and MLH1 219II/IV (Ptrend < 0.001) in Caucasians and ADPRT 762VA, ERCC2 751KQ/QQ and NBS1 185EQ/QQ in African-Americans (Ptrend = 0.006), respectively. Our results suggest that combined nsSNPs in multiple DNA repair pathways may contribute to breast cancer risk and larger studies are warranted to further evaluate polygenic models of DNA repair in breast cancer risk. [ABSTRACT FROM AUTHOR]

Prostate cancer (CaP) is the second leading cause of cancer death in American men. Chronic inflammation has been one of several factors associated with the development of CaP. Single-nucleotide polymorphisms (SNPs) in cytokine genes have been associated with increased inflammation, increased cytokine production and possibly increased CaP risk. However, the effects of cytokine SNPs on CaP susceptibility have not been consistent. Using the genomic DNA collected in a CaP case–control study (557 cases and 547 controls), we pilot tested the interactions of nine functionally characterized SNPs of three cytokine genes in CaP risk using the multivariate adaptive regression splines (MARS)–logit models. African-Americans with the IL10−819TT genotype had a lower CaP risk [odds ratio (OR) = 0.27, 95% confidence interval (CI) = 0.07–1.01], but subjects with the genotype combination of IL1B−511CT/TT and IL10−592CC had a higher CaP risk (OR = 2.56, 95% CI = 1.09–6.02). In Caucasians, higher CaP risk was associated with the IL10−1082AG/GG genotype (OR = 3.62, 95% CI = 1.42–9.28), the genotype combination of IL10−1082AA plus IL1B−31TT/TC (OR = 2.92, 95% CI = 1.13–7.55) and the genotype combination of TNF−238GG plus IL10−592AA (OR = 2.14, 95% CI = 1.05–4.38). Our results highlight the importance of cytokine SNPs and their interactions in CaP risk. [ABSTRACT FROM AUTHOR]