Impact of CCND1 A870G polymorphism on acute adverse events in postoperative rectal cancer patients treated with adjuvant concurrent chemoradiotherapy / 中华肿瘤杂志

<p><b>OBJECTIVE</b>The purpose of this study was to investigate the association between single nucleotide polymorphism (SNP) of CCND1 A870G and acute adverse events (AEs) in postoperative rectal cancer patients who received capecitabine-based postoperative chemoradiotherapy (CRT).</p><p><b>METHODS</b>Four hundred patients with stage II and III rectal cancer received postoperative CRT of capecitabine with or without oxaliplatin were accumulated and prostectively studied in this study. The patients were randomly divided into two groups. Two hundred and twenty-eight patients were treated with concurrent capecitabine and radiotherapy (Cap-CRT), and 172 patients were treated with capecitabine and oxaliplatin plus radiotherapy (Cap-Oxa-CRT). Adverse events were graded according to the Common Terminology Criteria for Adverse Events, v. 3.0 (CTCAE v3.0). The genotype of CCND1 A870G in the patients was detected by polymerase chain reaction-based restriction fragment length polymorphism (PCR-RFLP) analysis. The associations between the SNP and acute AEs were indicated by odds ratios (ORs) and 95% confidence intervals (CIs), which were computed with logistic regression model.</p><p><b>RESULTS</b>A total of 136 patients presented severe AEs. Among them the frequencies of the three genotypes GG, GA and AA were 16.9%, 50.7% and 32.4%, compared with 24.6%, 48.1% and 27.3%, respectively, among the patients without severe AEs. Diarrhea was the most common AE, and severe diarrhea occurred in 109 patients. The frequencies of the three genotypes GG, GA and AA were 15.6%, 47.7% and 36.7% among these patients, compared with 24.4%, 49.5% and 26.1%, respectively, among patients without severe diarrhea. Multivariate logistic regression analysis showed a 1.66-fold increased risk for severe diarrhea in patients with AA genotype (95%CI 1.03 - 2.67, P = 0.038) compared with the cases with GG or GA genotypes. Stratified analysis showed that in the Cap-Oxa-CRT group, patients with AA genotype showed a 2.34-fold increased risk for severe diarrhea (95%CI 1.16 - 4.76, P = 0.018) compared with those with GG or GA genotypes, but in the Cap-CRT group, the SNP was not associated with the risk of severe diarrhea.</p><p><b>CONCLUSIONS</b>The genetic polymorphism of CCND1 A870G might be a potential biomarker for predicting acute AEs in postoperative stage II and III rectal cancer patients treated with adjuvant concurrent chemoradiotherapy of capecitabine and oxaliplatin.</p>

A missense SNP in the codon of ADD1 phosphorylation site associated with non-cardia gastric cancer susceptibility in a Chinese population / 中华肿瘤杂志

<p><b>OBJECTIVE</b>This study investigated the association between a missense SNP in the codon of ADD1 phosphorylation site and the susceptibility of non-cardia gastric cancer in a Chinese population.</p><p><b>METHODS</b>PhosphoSitePlus and dbSNP database were combined to discover missense SNPs in the codon of phosphorylation site. Then, we genotyped the missense SNP in 1, 998 cases with non-cardia gastric cancer and 2, 008 cancer-free controls of Chinese descent. Analysis was conducted by using Logistic model adjusted by gender and age.</p><p><b>RESULTS</b>The rs4963 in the codon of ADD1 phosphorylation site was found. The frequencies of the 3 rs4963 genotypes, CC, CG, GG, among controls were 25.2%, 50.4%, and 24.4%, respectively, among patients were 20.1%, 50.6%, and 29.3%, respectively. Compared with CC genotype, the rs4963 CG genotype and GG genotype significantly increased the risk of non-cardia gastric cancer with the odds ratios being 1.24 (95%CI: 1.06 ∼ 1.46, P = 0.008) and 1.49 (95%CI: 1.25 ∼ 1.78, P < 0.001), respectively.</p><p><b>CONCLUSIONS</b>Fnnctional polymorphism in the phosphorylation site of ADD1 (rs4963) may influence the susceptibility of non-cardia gastric cancer.</p>

Association between HLA-DQA1 gene copy number polymorphisms and susceptibility to gastric cancer / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To explore the association between HLA-DQA1 gene copy number polymorphisms and gastric cancer risk in Chinese population, and the interaction of those genes and environmental factors.</p><p><b>METHODS</b>The genotype of HLA-DQA1 gene copy number polymorphisms was determined in 343 patients with gastric cancer and 330 controls by quantitative polymerase chain reaction. Logistic regression model was used to evaluate the impact of this polymorphism on the risk of developing gastric cancer and the gene-environment interaction.</p><p><b>RESULTS</b>Compared with 0 copy of HLA-DQA1 gene carriers, the 2 copies of HLA-DQA1 gene carriers had a significantly increased risk of gastric cancer (OR = 1.87, 95%CI = 1.15 - 3.06, P = 0.012). Gene-environment interaction of HLA-DQA1 gene copy number polymorphisms and Helicobacter pylori infection significantly increased the risk of gastric cancer in a multiplicative manner, with an OR of 3.89 (95%CI = 1.75 - 8.57, P = 0.001).</p><p><b>CONCLUSIONS</b>HLA-DQA1 gene copy number polymorphism is associated with gastric cancer susceptibility, and there is a multiplicative gene-environment interaction between this polymorphism and Hp infection in the development of gastric cancer.</p>

Association between genetic variations in tumor necrosis factor receptor genes and survival of patients with T-cell lymphoma / 癌症

The prognosis of T-cell lymphoma (TCL) has been shown to be associated with the clinical characteristics of patients. However, there is little knowledge of whether genetic variations also affect the prognosis of TCL. This study investigated the associations between single nucleotide polymorphisms(SNPs) in tumor necrosis factor receptor superfamily(TNFRSF) genes and the survival of patients with TCL. A total of 38 tag SNPs in 18 TNFRSF genes were genotyped using Sequenom platform in 150 patients with TCL. Kaplan-Meier survival estimates were plotted and significance was assessed using log-rank tests. Cox proportional hazard models were used to analyze each of these 38 SNPs with adjustment for covariates that might influence patient survival, including sex and international prognostic Index score. Hazard ratios (HRs) and their 95% confidence intervals(CIs) were calculated. Among the 38 SNPs tested, 3 were significantly associated with the survival of patients with TCL. These SNPs were located at LTβR (rs3759333C>T) and TNFRSF17(rs2017662C>T and rs2071336C>T). The 5-year survival rates were significantly different among patients carrying different genotypes and the HRs for death between the different genotypes ranged from 0.45 to 2.46. These findings suggest that the SNPs in TNFRSF genes might be important determinants for the survival of TCL patients.

Association between CTLA-4 gene polymorphism and susceptibility to cervical cancer / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To investigate the association between CTLA-4 +49A/G polymorphisms and the risk of susceptibility to cervical cancer.</p><p><b>METHODS</b>A hospital-based case-control study was conducted. 314 cases with primary cervical cancer and 320 healthy controls were collected and genotyped by PCR-based RFLP for +49A/G polymorphisms in the CTLA-4 gene.</p><p><b>RESULTS</b>The A allele and AA genotype of CTLA-4 gene were 32.5% and 9.6% in the patients, and 25.8% and 5.6% in the controls, respectively. Subjects with CTLA-4 +49AA genotype conferred a higher risk of cervical cancer (OR = 2.06, 95%CI: 1.10 - 3.85; P = 0.024). However, the correlation between AA genotype in CTLA-4 polymorphisms and clinicopathological characteristics was not significant.</p><p><b>CONCLUSION</b>The results of this study suggest that CTLA4 gene is associated with cervical cancer risk and may be a susceptible gene of cervical cancer.</p>

Polymorphisms of GSTP1 is associated with differences of chemotherapy response and toxicity in breast cancer / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Although chemotherapy is one of the most important treatments of breast cancer, it is limited by significant inter-individual variations in response and toxicity. The metabolism of epirubicin (EPI) and cyclophosphamide (CTX) is mainly mediated by cytochrome P450s (CYPs) and glutathione S-transferases (GSTs). It has been well-known that the activities of these enzymes are polymorphic in population due to their genetic polymorphisms. The aim of this research was to examine the effects of genetic polymorphisms in CYP3A, GSTP1 and MDR1 genes on treatment response and side-effects of breast cancer patients receiving EPI/CTX chemotherapy.</p><p><b>METHODS</b>One hundred and twenty patients with stage II or III invasive breast cancer were recruited and treated with three to four cycles of EPI 80 mg/m(2) and CTX 600 mg/m(2) every two weeks. The AJCC TNM staging system (sixth edition) was used to evaluate the pathological response of primary tumor and axillary lymph nodes. The genotypes of gene polymorphisms were determined by using PCR-restriction fragment length polymorphism methods.</p><p><b>RESULTS</b>Patients carrying GSTP1 (105)Ile/Val or (105)Ile/Ile genotype were more likely to have good response (OR, 0.40; 95%CI, 0.16 - 0.96; P = 0.024) and light toxicity (OR, 0.35; 95%CI, 0.13 - 0.78; P = 0.006) than those carrying (105)Val/Val genotypes. The response to the treatment was not correlated with estrogen receptor, progesterone receptor and Her2/neu status of tumors. No correlation was found between toxicity effect and patient's age, tumor staging, menopause status, and dose intensity of the drugs.</p><p><b>CONCLUSION</b>GSTP1 polymorphism was associated with the chemotherapy response or adverse effects of EPI and CTX regimens.</p>

A single nucleotide polymorphism in the matrix metalloproteinase 2 promoter is closely associated with high risk of nasopharyngeal carcinoma in Cantonese from southern China / 癌症

Matrix metalloproteinase 2 (MMP2) has been shown to play an important role in several steps of cancer development. The -1306C/T polymorphism of the MMP2 gene displays a strikingly lower promoter activity than the T allele, and the CC genotype in the MMP2 promoter has been reported to associate with the development of several cancers. To assess the contribution of the MMP2 -1306C/T polymorphism to the risk of nasopharyngeal carcinoma (NPC), we conducted a case-control study and analyzed MMP2 genotypes in 370 patients with NPC and 390 frequency-matched controls using real-time PCR-based TaqMan allele analysis. We found that subjects with the CC genotype had an increased risk (OR = 1.55, 95% CI = 1.05-2.27) of developing NPC compared to those with the CT or TT genotypes. Furthermore, we found that the risk of NPC was markedly increased in subjects who were smokers (OR = 15.04, 95% CI = 6.65-33.99), heavy smokers who smoked ≥ 20 pack-years (OR = 18.66, 95% CI = 7.67-45.38), or young (<60 years) at diagnosis (OR = 1.52, 95% CI = 1.01-2.29). Our results provide molecular epidemiological evidence that the MMP2 -1306C/T promoter polymorphism is associated with NPC risk, and this association is especially noteworthy in heavy smokers.

The association between polymorphism of transforming growth factor-β1 and radiochemotherapy response and survival in esophageal squamous cell carcinoma patients / 中华预防医学杂志

<p><b>OBJECTIVE</b>To evaluate the association between polymorphism of transforming growth factor-β1 (TGF-β1)-509C/T and radiochemotherapy response and survival in esophageal squamous cell carcinoma (ESCC) patients.</p><p><b>METHODS</b>The genotype of TGF-β1-509C/T was detected by polymerase chain reaction-based restriction fragment length polymorphism assay (PCR-RFLP) in 230 ESCC patients receiving radiotherapy alone or in combination with chemotherapy. Unconditional multivariate logistic regression analysis was done to estimate adjusted odds ratios (ORs) along with the corresponding 95% confidence intervals (CIs) for the polymorphism and radiochemotherapy response. The associations between overall survival time or hazard ratio (HR) of ESCC patients and genetic variation or the clinical data were estimated by applying univariate and multivariate Cox-regression analyses.</p><p><b>RESULTS</b>Among 208 patients with upper gastrointestinal contrast assessment, 87 cases were susceptible to radiochemotherapy treatment and the TGF-β1-509CC, CT and TT genotype patients were 17 (19.5%), 48 (55.2%) and 22 (25.3%), respectively. Among the patients who were insensitive to radiochemotherapy treatment (n = 121), the TGF-β1-509CC, CT and TT genotype patients were 39 (32.2%), 54 (44.6%) and 28 (23.2%), respectively. Compared with TGF-β1-509CC genotype, the CT and TT genotype carriers had a significantly better treatment response (adjusted OR = 2.07, 95%CI, 1.05 - 4.09, P = 0.036). The median survival time of CC genotype patients was 17.0 (95%CI, 12.0 - 23.0) months, CT genotype patients was 22.0 (95%CI, 16.0 - 33.0) months and TT genotype patients was 25.0 (95%CI, 15.0 - 41.0) months. Compared to CC genotype patients, the survival time difference of CT and TT group was close to the statistical break point (P = 0.063). Our data showed that the subjects with CT or TT genotype had an decreased HR respectively as compared with those with CC genotype (CT, adjusted HR = 0.81, 95%CI, 0.52 - 1.24; TT, adjusted HR = 0.86, 95%CI, 0.65 - 1.12), but the difference was not statistically significant (P > 0.05). However, tumor location, clinical stage and radiochemotherapy response affected the overall survival time of the patient significantly (adjusted HR = 1.28, 95%CI: 1.01 - 1.61, P = 0.040; 1.49, 95%CI, 1.17 - 1.88, P = 0.001; 1.55, 95%CI, 1.06 - 2.26, P = 0.023, respectively).</p><p><b>CONCLUSION</b>These results suggest that TGF-β1-509C/T polymorphisms were associated with radiochemotherapy for esophageal squamous cell carcinoma which might be genetic markers for prediction of the radiochemotherapy response in ESCC patients.</p>

Functional Bax polymorphism associated with lung cancer susceptibility / 中华肿瘤杂志

<p><b>OBJECTIVE</b>The Bcl-2 associated X protein (Bax), belonging to the Bcl-2 family, plays a pivotal role in mitochondria-dependent apoptosis. The aims of this study are to revalidate the functional significance of Bax G(-248)A polymorphism, and investigate its association with lung cancer risk in Chinese population.</p><p><b>METHODS</b>The biological function of Bax G(-248)A was tested by luciferase assays, and its effects on lung cancer risk was determined by case-control analysis of 989 patients with lung cancer and 990 controls.</p><p><b>RESULTS</b>Bax -248A allele exhibited significantly higher transcriptional activity compared with G allele. The Bax-248A allele carriers yielded a significantly decreased risk of lung cancer, compared with -248G allele carriers (OR = 0.68, 95% CI = 0.48 approximately 0.90, P = 0.01). Furthermore, a significant gene-smoking interaction between Bax G(-248)A polymorphism and smoking existed among the light smokers.</p><p><b>CONCLUSION</b>Bax G(-248)A polymorphism is associated with lung cancer susceptibility in Chinese population.</p>

Genetic polymorphisms in STK15 and MMP-2 associated susceptibility to esophageal cancer in Mongolian population / 中华预防医学杂志

<p><b>OBJECTIVE</b>To investigate the frequencies of alleles and the association with risk of esophageal cancer in a Mongolian population, and to compare the allele frequencies of these polymorphisms between the two populations and the susceptibility to esophageal cancer.</p><p><b>METHODS</b>A case-control study was conducted, and 8 single nucleotide polymorphisms (SNP), including FAS - 670G/A, FAS - 1377G/A, FASL -844T/C, COX-2 - 1290A/G, COX-2 - 1195G/A, STK15 Phe31Ile, MMP-2 - 1306C/T and MMP -2 -735C/T, were detected by polymerase chain reaction-based restriction fragment length polymorphism assay (PCR-RFLP) in 188 esophageal cancer cases and 324 normal controls of Mongolian. The odds ratios (ORs) and 95% confidence intervals (CIs) were calculated by unconditional logistic regression. The results were then compared with the reported data of the Han ethnic Chinese population.</p><p><b>RESULTS</b>In Mongolian, as compared with the STK15 31Ile/Ile genotype, the STK15 31Phe/Phe genotype carriers had an increased risk of esophageal cancer (adjusted OR = 2.20, 95% CI: 1.12-4.31), and the subjects with MMP-2 - 735TT genotype had an increased risk of esophageal cancer as compared with those with the MMP-2 - 735CC genotype (adjusted OR =4.82, 95% CI: 1.59 - 14.60). However, the rest of SNPs were not associated with the susceptibility to esophageal cancer. The allele frequencies of FASL - 844 T/C [0.264(171/648)/0.736 (477/648), 0.323(418/1296)/0.677(878/1296)], COX-2 - 1195G/A [0.431(279/648)/0.569(369/ 648), 0.492(1250/2540)/0.508(1290/2540)], MMP-2 - 1306C/T [0.869(563/648)/0.131(85/ 648), 0.835(1298/1554)/0.165(256/1554)] and MMP-2 - 735C/T [0.789(511/648)/0.211(137/ 648), 0.748(1163/1554)/0.252(391/1554)] were significantly different between the ethnic populations (chi2 = 7.03, 7.84, 3.94, 4.05, respectively, P <0.05).</p><p><b>CONCLUSION</b>These findings suggested that STK15 Phe31Ile and MMP-2 -735C/T polymorphisms might be the genetic susceptibility factors for esophageal cancer in Mongolian and there should be some differences of genetic susceptibility to esophageal cancer in between Han ethnic Chinese and Mongolian population.</p>

Association between Fas/Fas L genes promoter polymorphisms and pathogenic risk of cervical cancer / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To investigate the association between apoptosis genes Fas/Fas L promoter polymorphisms and the risk of the development of cervical cancer.</p><p><b>METHODS</b>Blood samples were collected from 314 cases with primary cervical cancer and 615 healthy controls. Genotypes of Fas/Fas L genes were determined by polymerase chain reaction-based restriction fragment length polymorphism. The associations with the risk of cervical cancer and impact of clinicopathological characteristics were estimated by logistic regression.</p><p><b>RESULTS</b>Fas L-844CC genotype was significantly associated with increased risk of cervical cancer compared with Fas L-844TC or -TT genotype (OR = 3.05; P < 0.01). However, there was no significant difference of Fas-670A/G or -1377G/A genotypes. Interaction of genetic polymorphism between Fas and Fas L was observed. Stratification analysis revealed that Fas-670G or -1377A allele was significantly higher in squamous carcinoma in situ (OR = 1.77 or 1.93; P < 0.05) while Fas L-844CC genotype had an increased risk of invasive squamous carcinoma compared with that of Fas L-844TT genotype (OR = 3.33; P < 0.01). No significant associations were observed between polymorphisms in Fas/Fas L and clinical FIGO stage, cell differentiation, size of tumors, serum squamous cell carcinoma antigen value at the diagnosis and so on.</p><p><b>CONCLUSION</b>The results of this study suggest that genetic polymorphisms of Fas and Fas L in apoptotic pathway are associated with the risk of development of cervical carcinoma.</p>

Genetic polymorphism in MDM2 is associated with susceptibility to colorectal cancer in a Chinese population / 中华肿瘤杂志

<p><b>OBJECTIVE</b>The tumor suppressor p53 pathway plays a crucial role in preventing carcinogenesis through its ability to impose cell cycle arrest and apoptosis following DNA damage or oncogene activation. Mouse double minute 2 (MDM2) gene is a key negative regulator of p53 pathway and overexpressed in many cancers as oncoprotein. We have previously shown that genetic polymorphisms in the MDM2 promoter (309T --> G) and p53 coding region (72Arg --> Pro) are associated with susceptibility to esophageal and lung cancers. This study investigated the associations between these polymorphisms in p53 and MDM2 and risk of the occurrence and progression of colorectal cancer.</p><p><b>METHODS</b>Genotypes of 1000 Chinese colorectal cancer patients and 1300 controls were determined by PCR-based restriction fragment length polymorphism or tetra-primer amplification refractory mutation system-PCR. Associations with risk of colorectal cancer were estimated by unconditional logistic regression.</p><p><b>RESULTS</b>An increased colorectal cancer risk associated with the MDM2 GG [odds ratio (OR) = 2.06, 95% confidence interval (CI) = 1.62-2.62] or TG (OR = 1.31, 95% CI = 1.06-1.62) genotype was observed compared with the TT genotype. No association was found between p53 polymorphism and risk of the cancer, with the ORs being 0.87 (95% CI = 0.68-1.11) for the Pro/Pro and 0. 85 (95% CI = 0.70-1.04) for the Arg/Pro genotype compared with the Arg/Arg genotype. However, combined analysis of MDM2 and p53 polymorphisms showed that compared with subjects carrying both MDM2 TT and p53 Arg/Arg genotypes, the OR for subjects carrying both MDM2 GG and p53 Pro/Pro genotypes was 2.75 (95% CI = 1.60-4.70), significantly higher than that for subjects carrying both MDM2 TT and p53 Pro/Pro genotypes (OR = 1.09, 95% CI = 0.63-1.88).</p><p><b>CONCLUSION</b>These results suggest that genetic polymorphism in MDM2 may be associated with susceptibility to colorectal cancer in a Chinese population.</p>

Association of genetic polymorphisms in selenoprotein GPX1 and TXNRD2 with genetic susceptibility of gastric cancer / 中华预防医学杂志

<p><b>OBJECTIVE</b>This study examined whether the two polymorphisms of GPX1 (198Pro--> Leu) and TXNRD2 (370Lys-->Arg) contributed alone or in combination, to the risk of gastric cancer development.</p><p><b>METHODS</b>A total of 361 patients with gastric cancer and 363 cancer-free controls were recruited and their genotypes of the two polymorphisms were determined by polymerase chain reaction-based restrictive fragment length polymorphism (PCR-RFLP) method. Odds ratio (OR) and 95% confidence interval (CI) were computed using unconditional logistic regression model.</p><p><b>RESULTS</b>GPX1 and TXNRD2 polymorphisms individually were not associated with the risk of gastric cancer. Gene-gene interaction of GPX1 and TXNRD2 polymorphisms decreased the risk of gastric cancer. Carrying the protective genotype might decrease the risk at 62% (OR = 0.38, 95% CI = 0.26-0.55, P < 0.001) as compared with the risk genotype.</p><p><b>CONCLUSION</b>The GPX1 198 Pro/Pro and TXNRD2 370Arg/Arg genotypes might be associated with the genetic susceptibility of gastric cancer.</p>

Association between mthfr gene polymorphisms and toxicity of HDMTX chemotherapy in acute lymphocytic leukemia / 中国实验血液学杂志

This study was aimed to investigate the association between mthfr gene polymorphisms and toxicity of HDMTX in acute lymphocytic leukemia patients. A total of 44 patients were selected, and DNA was extracted from their peripheral blood. PCR-RFLP was used to determine the genotypes of mthfr. The toxicity response of patients received HDMTX chemotherapy was observed. The results showed that the toxicity of HDMTX to carriers of the variant allele at codon 677 (CT or TT) increased, as compared with individuals with the common CC genotype (OR = 3.75, 95% CI 1 - 14, p = 0.04). In contrast, the toxicity of HDMTX to ALL patients with the variant allele at codon 1298 (AC or CC) decreased as compared with the common AA genotype carriers (OR = 0.12, 95% CI: 0.026 - 0.564, p = 0.007). As compared with carriers of the variant allele at coden 1298 (AC or CC), the toxicity of HDMTX to patients with TT genotype at 677 and AA genotype at 1298 increased (OR = 16.5, 95% CI: 0.026 - 0.564). It is concluded that mthfr gene polymorphisms associate with the toxicity of HDMTX chemotherapy in acute lymphocytic leukemia.

Association between genetic polymorphism in DNA repair genes XRCC3 and risks of laryngeal and hypopharyngeal carcinomas / 中华耳鼻咽喉头颈外科杂志

<p><b>OBJECTIVE</b>To study the association between polymorphism of DNA repair gene XRCC3 Thr 241 Met and the risks of developing laryngeal and hypopharyngeal carcinomas.</p><p><b>METHODS</b>One hundred and seventy five patients with laryngeal or hypopharyngeal carcinoma and 525 cancer-free controls were genotyped for the polymorphism by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). The odds ratios (ORs) and 95% confidence intervals (CIs) were calculated using unconditional logistic regression model.</p><p><b>RESULTS</b>The XRCC3 241 Met allele increased the risk of developing laryngeal carcinoma and hypopharyngeal carcinoma. Comparing with subjects having the XRCC3 241 Thr/Thr genotype, the subjects at least having one XRCC3 241 Met allele had OR of 2. 26 (95% CI 1.33 -3.82). Respectively analyzing the risks of laryngeal carcinoma and hypopharyngeal carcinoma, The allele XRCC3 241 Met increased the risks of developing both laryngeal and hypopharyngeal carcinoma. Comparing with the subjects having the XRCC3 241 Thr/Thr genotype, the subjects with laryngeal carcinoma at least having one XRCC3 241 Met genotype had OR of 2.27 (95% CI 1.26 - 4.09); the subjects with hypopharyngeal carcinoma at least having one XRCC3 241 Met genotype had OR of 2. 99 (95% CI 1.27 - 7.04). Smoking may increase the risk of developing laryngeal carcinoma and hypopharyngeal carcinoma. The interaction of smoking and XRCC3 Thr241 Met increased risk of laryngeal carcinoma and hypopharyngeal carcinoma in a super-multiplicative manner. The subjects with heavy smoking and at least having one XRCC3 241Met allele had OR of 19.09 (95% CI 7.38 -49.40) comparing with those having the XRCC3 241 Thr/ Thr genotype and no smoking, which was greater than the multiplication of ORs both of subjects at least having one 241 Met allele meanwhile without smoking (OR, 0.91; 95% CI, 0.20 - 4.21) and of subjects having XRCC3 241 Thr/Thr genotype meanwhile with smoking (OR, 4.13; 95% CI, 2.38 - 7.17).</p><p><b>CONCLUSIONS</b>XRCC3 Thr 241 Met plays an important role in the development of laryngeal and hypopharyngeal carcinoma.</p>

Association between genetic polymorphism in xeroderma pigmentosum G gene and risks of laryngeal and hypopharyngeal carcinomas / 中国医学科学院学报

<p><b>OBJECTIVE</b>To study the association between polymorphism of DNA repair gene xeroderma pigmentosum G (XPG) Asp1104His and the risks of developing laryngeal and hypopharyngeal carcinomas.</p><p><b>METHODS</b>Totally 175 patients with laryngeal or hypopharyngeal carcinoma and 525 cancer-free controls were genotyped for the polymorphism by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). The odds ratio (OR) and 95% confidence interval (CI) were calculated using unconditional logistic regression model.</p><p><b>RESULTS</b>Compared with those having the Asp/Asp genotype, patients having the XPG 1104Asp/His genotype had a higher risk for laryngeal carcinoma (OR = 2.46, 95% CI = 1.15-5.24, P < 0.05), but not for hypopharyngeal carcinoma (OR = 1.36, 95% CI = 0.87-2.12, P > 0.05). In addition, the XPG 1104Asp/His genotype appeared to be associated with well differentiated squamous cell carcinoma in both larynx and hypopharynx (OR = 1.88, 95% CI = 1.05-3.40, P < 0.05 ).</p><p><b>CONCLUSION</b>The XPG Asp1104His polymorphism may play a role in the development of laryngeal and hypopharyngeal carcinomas.</p>

Genetic polymorphisms in the promoter region of cyclooxygenase-2 and their association with risk of gastric cancer / 中国医学科学院学报

<p><b>OBJECTIVE</b>To examine the genetic polymorphisms in the promoter region of cyclooxygenase-2 ( COX-2) and evaluate their association with the risk of gastric cancer.</p><p><b>METHODS</b>Single-strand conformational polymorphism and DNA sequencing were used to screen the genetic variants of the COX-2 promoter region. Total 323 patients with gastric cancer and 646 frequency-matched controls were genotyped by polymerase chain reaction-restriction fragment length polymorphism method. Odds ratios (OR) and 95% confidence intervals (CI) were estimated by logistic regression. Haplotype frequency was estimated using Haplo. stat software.</p><p><b>RESULTS</b>Three single nucleotide polymorphisms, including - 1290A > G, -1195G > A, and -765G > C were identified in the promoter of COX- 2. Case-control analysis showed an increased risk of developing gastric cancer for the -1290AG (OR 1.64; 95% CI 1.03-2.61), -1195AA (OR 2.68; 95% CI 1.65-4.33), and -765CG (OR 2.66; 95% CI 1.53-4.64) genotype carriers, respectively, compared with noncarriers. A greater risk of developing gastric cancer was observed for the A(-1290) -A(-1195) -C(-765) haplotype compared with the A(-1290) -G(-1195) -G(-765) haplotypes (OR 11.80; 95% CI 2.43-57.25).</p><p><b>CONCLUSION</b>Genetic polymorphisms in COX-2 promoter region may play a role in gastric carcinogenesis.</p>

Association between genetic polymorphism in STK15 and risk of colorectal cancer in a Chinese population / 中华肿瘤杂志

<p><b>OBJECTIVE</b>This case-control study was designed to detect the association between STK15 Phe31Ile polymorphism and colorectal cancer.</p><p><b>METHODS</b>Genotypes were determined in 283 patients with colorectal cancer and 283 controls. The adjusted odds ratios (ORs) and 95% confidence intervals (CIs) were calculated using logistic regression model.</p><p><b>RESULTS</b>The frequency of the STK15 Ile/Ile genotype was significantly higher in cancer cases than in controls (50.2% vs. 36.8%; P = 0.02). Subjects with the Ile/Ile genotype had an increased risk for the occurrence of colorectal cancer compared with those with the STK15 Phe/Phe genotype (adjusted OR, 1.92; 95% CI, 1.13 - 3.27). No significant association was observed between this STK15 polymorphism and risk of metastasis of the cancer.</p><p><b>CONCLUSION</b>These findings suggest that STK15 Phe/Ile polymorphism may be a genetic susceptibility factor for colorectal cancer among Chinese.</p>

Association of the responsiveness of advanced non-small cell lung cancer to platinum-based chemotherapy with p53 and p73 polymorphisms / 中华肿瘤杂志

<p><b>OBJECTIVE</b>It has been proposed that genetic polymorphisms in apoptosis-related genes might be associated with sensitivity of cancer cells to platinum-based chemotherapy. This study examined the relationship between p53 and p73 genetic polymorphisms and the response to platinum-based chemotherapy in patients with advanced non-small cell lung cancer (NSCLC).</p><p><b>METHODS</b>A total of 165 patients with advanced NSCLC treated with platinum-based chemotherapy were genotyped for the p53 codon 72 Pro-->Arg and p73 exon 2 G4C14-->A4T14 polymorphisms using PCR-RFLP and ARMS-PCR assays. Clinical response to the chemotherapy was obtained after 2 to 3 cycles. The adjusted odds ratios (ORs) and 95% confidence intervals (CIs) were calculated using unconditional logistic regression model. All statistical tests were two-sided.</p><p><b>RESULTS</b>The p53 Pro allele carriers had higher response rate than non-carriers (OR = 2.46; 95% CI = 1.11 - 5.45). A higher response rate was also observed for the p73 G4C14/A4T14 or A4T14/A4T14 genotype, compared with the G4C14/G4C14 genotype (OR = 2.22; 95% CI = 1.14 - 4.30). When these two polymorphisms were combined to be analyzed, it was found that the response rate in those carrying the wild-type genotypes at both genes was only 7.7%, whereas the response rates in patients carrying 1, 2, or more than 2 variant alleles of p53 and p73 were 34.8%, 42.2% and 40.7%, respectively.</p><p><b>CONCLUSION</b>Those results suggest that p53 and p73 polymorphisms may be associated with clinical responsiveness to platinum-based chemotherapy in advanced NSCLC.</p>

XRCC1 and XPD genetic polymorphisms predict clinical responses to platinum-based chemotherapy in advanced non-small cell lung cancer / 中华肿瘤杂志

<p><b>OBJECTIVE</b>DNA repair system plays an important role in tumor sensitivity to platinum-based chemotherapy. The purpose of this study was to examine the association between polymorphisms in XRCC1 and XPD, which are involved in DNA repair, and clinical responses to platinum-based chemotherapy in advanced non-small cell lung cancer (NSCLC).</p><p><b>METHODS</b>XRCC1 Arg194Trp and XPD Lys751Gln were genotyped by PCR-RFLP method in 200 patients with advanced NSCLC who received platinum-based chemotherapy. Unconditional logistic regression model was used to analyze the association between genetic polymorphisms and clinical responses.</p><p><b>RESULTS</b>The overall response rate (CR + PR) was 36.0%, including 1 CR, 72 PR, 94 SD and 34 PD. The XRCC1 194Trp allele carriers had higher response rate than the subjects with the Arg/Arg genotype (adjusted OR, 2.48; 95% CI, 1.36 - 4.51, P = 0.003). However, the XPD Lys751Gln polymorphism was not found to be associated with the platinum-based chemotherapy. These two genetic polymorphisms may have some interaction in the drug sensitivity, the P value for the trend was significant (P = 0.004).</p><p><b>CONCLUSION</b>Those results suggest that the XRCC1 Arg194Trp and XPD Lys751Gln genetic polymorphisms may be associated with clinical responses to platinum-based chemotherapy in advanced non-small cell lung cancer.</p>