| Excision repair cross-complementing group2 (ERCC2)/Xeroderma pigmentosum complementation group D (XPD), is DNA helicase, involved in nucleotide excision repair and basal transcription. The functional significance of ERCC2/XPD variants has not yet been elucidated, but some of variants may be associated with reduced repair capacity and increased cancer susceptibility. In the present study, we wish to test the hypothesis that genetic variations in ERCC2/XPD Arg156Arg (C22541A) may be a marker for breast cancer susceptibility in Chinese population.Material and method1. Researched cohortThis hospital-based case-control study consisted of 129 cases with breast cancer and 205 cancer-free controls. All subjects were unrelated ethnic Han Chinese from North-Eastern China. The cases with newly diagnosed primary breast cancer were recruited between March 2004 and December 2006 at Liaoning People's Hospital, Affiliated first Hospital of Liaoning Mediacal College and The General Hospital of Shenyang Military Region. All cases were previously untreated (prior to chemotherapy or radiotherapy for cancer). Population controls were accrued from non-cancer patients admitted to the bone wards in the same region. Randomly selected controls were matched to the cases by age (±3 years), gender and ethnicity.2. GenotypingThe ERCC2/XPD Arg156Arg (C22541A) (rs238406) polymorphism was detected using a modified PCR-RFLP method. The PCR primers were synthesized by Takara Biotechnology (Dalian) Co., Ltd, China. Primers were: forward primer 5'-TGG AGT GCT ATG GCA CGA TCT CT-3'and reverse primer 5'-CCA TGG GCA TCA AAT TCC TGG GA-3'. 10 ml PCR product was digested with three units of Tfi I enzyme (New England Biolabs, Beverly, MA). The three possible genotypes were defined by three distinct banding patterns: CC (587- and 57-bp fragments), AC (587-, 474-, 113-, and 57-bp fragments), and AA (474-, 113-, and 57-bp fragments).3. Statistical analysisHWE software (http://linkage.rockefeller.edu/linkutil.htm) was used for Hardy–Weinberg equilibrium test. The ORs and 95% CIs were calculated to assess the relationship between the polymorphism and breast cancer. Theχ2 test was used to compare the distribution of the genotypes between breast cancer cases and controls. OR and 95% CI were calculated to evaluated risk between genotypes and breast cancer and risk between genotypes and early breast cancer, respectively. All analyses were performed using SPSS software (version 11.5, USA). ResultsThere was no statistically significant difference in mean age and gender distribution between the cases and controls. There were more subjects with family history of breast cancer among cases (6.2%) than among controls (1.0%) (P=0.016).The genotype distribution of ERCC2/XPD Arg156Arg (C22541A) were in Hardy–Weinberg equilibrium for case and control subjects (P=0.15 and P=0.96, respectively). The frequency of the variant A allele in ERCC2/XPD C22541A was 0.48 in the Control population. Which is in agreement with our previous report (controls: A=0.49) in Chinese lung cancer population. But which is disagreement with the average frequency (A= 0.44) in previously reported Caucasian populations (χ2 =4.881, P=0.034).No significant events were found between polymorphism of ERCC2/XPD Arg156Arg and susceptibility of breast cancer(AA/AC vs. CC: OR=1.27, 95%CI=0.78-2.06, P=0.330;AA vs. CC: OR=1.12, 95%CI=0.61-2.04, P=0.717; AC vs CC: OR=1.36, 95%CI=0.81-2.28, P=0.248). There were no differences in susceptibility estimates according to age at onset of cancer and menopause and cancer occurrence.DiscussionSome studies have investigated associations between ERCC2/XPD variants in DNA repair genes and cancer risk. The most extensively studied single nucleotide polymorphisms of ERCC2/XPD are Asp312Asn and Lys751Gln. However, the results from epidemiologic studies have been inconsistent.To our knowledge, the present study is the first to deal with the ERCC2/XPD Arg156Arg (C22541A) polymorphism in relation to breast cancer risk in a Chinese population. Contrary to our previous findings among Chinese lung cancer, we found no evidence supporting the hypothesis that breast cancer susceptibility is associated with DNA nucleotide excision repair gene ERCC2/XPD Arg156Arg (C22541A) polymorphism in this Chinese population. With the present genotype distribution, studies of large samples will be need among cases and controls if we had 90% chance of detecting an OR of 2 between homozygote carriers of the A-allele and carriers of the C-allele at a 0.05 significance level. The frequency of the variant A allele in ERCC2/XPD C22541A was 0.48 in the control population. Which is in agreement with our previous report (controls: A=0.49) in Chinese lung cancer population. But which is disagreement with the average frequency (A =0.44) in previously reported Caucasian populations (χ2 =4.881, P=0.03).Genetic factor may result in early onset of cancer. However, no statistically significant effects were found for analyses of the odds ratios on ERCC2/XPD Arg156Arg (C22541A) and total and early onset breast cancer and menopause and cancer occurrence.ConclusionIn conclusion, these findings suggest that the ERCC2/XPD Arg156Arg (C22541A) polymorphism may play a limited role for breast cancer susceptibility in this Chinese population. Further studies considering larger number of subjects and interaction with other genetic polymorphisms within the 19q13.2 ~3 region should be undertaken in Chinese populations. |
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