Cratoxylum formosum dyer extract alleviates testicular damage in hypertensive rats.

The effects of a Cratoxylum formosum (Jack) Dyer ssp. (CF) extract on testicular damage were assessed in hypertensive rats. Nω -nitro-L-arginine methyl ester hydrochloride (L-NAME; 40 mg kg-1  day-1 ) was administered for 5 weeks to induce hypertension in male Sprague-Dawley rats, and treated with CF extract (100, 300 or 500 mg kg-1  day-1 ) or sildenafil (5 mg kg-1  day-1 ) during the final 2 weeks (n = 8/group). Biochemical components of the CF extract were identified and mainly contained phenolic compounds. The CF extract significantly reduced systolic blood pressure and alleviated impaired sperm quality and seminiferous tubular morphology in hypertensive rats. CF extract restored reduced serum testosterone and protein expression of steroidogenic acute regulatory protein (StAR), nuclear factor erythroid-related factor 2 (Nrf2), and haem oxygenase 1 (HO-1) in L-NAME rats. Hypertensive rats presented decreased antioxidant enzyme activities, and increased testicular and plasma malondialdehyde (MDA) levels and superoxide production, all of which were normalised by CF extract. Furthermore, endothelial nitric oxide synthase (eNOS) expression in testicular tissue and plasma nitrate/nitrite levels were restored in hypertensive rats administered CF extract. Conclusion: CF extract alleviated testicular damage in hypertensive rats. Potential molecular mechanisms may involve suppression of oxidative stress and restoration of StAR, Nrf2, HO-1 and eNOS expression in hypertensive rats.

Geographical distribution and risk association of human papillomavirus genotype 52-variant lineages.

Human papillomavirus (HPV) genotype 52 is commonly found in Asian cases of cervical cancer but is rare elsewhere. Analysis of 611 isolates collected worldwide revealed a remarkable geographical distribution, with lineage B predominating in Asia (89.0% vs 0%-5.5%; P(corrected) < .001), whereas lineage A predominated in Africa, the Americas, and Europe. We propose that the name "Asian lineage" be used to denote lineage B, to signify this feature. Preliminary analysis suggested a higher disease risk for lineage B, although ethnogeographical confounders could not be excluded. Further studies are warranted to verify whether the reported high attribution of disease to HPV52 in Asia is due to the high prevalence of lineage B.

Geographical distribution and oncogenic risk association of human papillomavirus type 58 E6 and E7 sequence variations.

Human papillomavirus (HPV) 58 accounts for a notable proportion of cervical cancers in East Asia and parts of Latin America, but it is uncommon elsewhere. The reason for such ethnogeographical predilection is unknown. In our study, nucleotide sequences of E6 and E7 genes of 401 HPV58 isolates collected from 15 countries/cities across four continents were examined. Phylogenetic relationship, geographical distribution and risk association of nucleotide sequence variations were analyzed. We found that the E6 genes of HPV58 variants were more conserved than E7. Thus, E6 is a more appropriate target for type-specific detection, whereas E7 is more appropriate for strain differentiation. The frequency of sequence variation varied geographically. Africa had significantly more isolates with E6-367A (D86E) but significantly less isolates with E6-203G, -245G, -367C (prototype-like) than other regions (p ≤ 0.003). E7-632T, -760A (T20I, G63S) was more frequently found in Asia, and E7-793G (T74A) was more frequent in Africa (p < 0.001). Variants with T20I and G63S substitutions at E7 conferred a significantly higher risk for cervical intraepithelial neoplasia grade III and invasive cervical cancer compared to other HPV58 variants (odds ratio = 4.44, p = 0.007). In conclusion, T20I and/or G63S substitution(s) at E7 of HPV58 is/are associated with a higher risk for cervical neoplasia. These substitutions are more commonly found in Asia and the Americas, which may account for the higher disease attribution of HPV58 in these areas.

Limonin ameliorates cardiovascular dysfunction and remodeling in hypertensive rats.

AIMS: Limonin is a tetracyclic triterpenoid isolated from citrus fruits. Here, the effects of limonin on cardiovascular abnormalities in nitric oxide-deficient rats induced by Nω-Nitrol-arginine methyl ester (L-NAME) were explored. MAIN METHODS: Male Sprague Dawley rats were given L-NAME (40 mg/kg, drinking water) for 3 weeks and then treated daily with polyethylene glycol (vehicle), limonin (50 or 100 mg/kg) or telmisartan (10 mg/kg) for two weeks. KEY FINDINGS: Limonin (100 mg/kg) markedly reduced L-NAME-induced hypertension, cardiovascular dysfunction and remodeling in rats (P < 0.05). Increases in systemic angiotensin-converting enzyme (ACE) activity and angiotensin II (Ang II) and a reduction in circulating ACE2 were restored in hypertensive rats treated with limonin (P < 0.05). Reductions in antioxidant enzymes and nitric oxide metabolites (NOx) and increases in oxidative stress components induced by L-NAME were relieved by limonin treatment (P < 0.05). Limonin suppressed the increased expression of tumor necrosis factor-α (TNF-α) and interleukin (IL)-6 in cardiac tissue and circulating TNF-α in rats that received L-NAME (P < 0.05). Changes in Ang II receptor type I (AT1R), Mas receptor (MasR), nuclear factor kappa-light-chain-enhancer of activated B cells (NF-ĸB) and NADPH oxidase subunit 2 (gp91phox) protein expression in cardiac and aortic tissue were normalized by limonin (P < 0.05). SIGNIFICANCE: In conclusion, limonin ameliorated L-NAME-induced hypertension, cardiovascular dysfunction and remodeling in rats. These effects were relevant to restorations of the renin-angiotensin system, oxidative stress and inflammation in NO-deficient rats. The molecular mechanisms are associated with the modulation of AT1R, MasR, NF-ĸB and gp91phox protein expression in cardiac and aortic tissue.

Identification of human papillomavirus type 58 lineages and the distribution worldwide.

BACKGROUND: Human papillomavirus type 58 (HPV-58) accounts for a much higher proportion of cervical cancers in East Asia than other types. A classification system of HPV-58, which is essential for molecular epidemiological study, is lacking. METHODS AND RESULTS: This study analyzed the sequences of 401 isolates collected from 15 countries and cities. The 268 unique concatenated E6-E7-E2-E5-L1-LCR sequences that comprised 57% of the whole HPV-58 genome showed 4 distinct clusters. L1 and LCR produced tree topologies that best resembled the concatenated sequences and thus are the most appropriate surrogate regions for lineage classification. Moreover, short fragments from L1 (nucleotides 6014-6539) and LCR (nucleotides 7257-7429 and 7540-52) were found to contain sequence signatures informative for lineage identification. Lineage A was the most prevalent lineage across all regions. Lineage C was more frequent in Africa than elsewhere, whereas lineage D was more prevalent in Africa than in Asia. Among lineage A variants, sublineage A2 dominated in Africa, the Americas, and Europe, but not in Asia. Sublineage A1, which represents the prototype that originated from a patient with cancer, was rare worldwide except in Asia. CONCLUSIONS: HPV-58 can be classified into 4 lineages that show some degree of ethnogeographic predilection in distribution. The evolutionary, epidemiological, and pathological characteristics of these lineages warrant further study.

Nobiletin resolves left ventricular and renal changes in 2K-1C hypertensive rats.

This study investigated the effects of nobiletin on cardiorenal changes and the underlying mechanisms involved in two-kidney, one-clip (2K-1C) hypertension. 2K-1C rats were treated with nobiletin (15 or 30 mg/kg/day) or losartan (10 mg/kg/day) for 4 weeks (n = 8/group). Nobiletin (30 mg/kg) reduced high levels of blood pressure and circulating angiotensin II and angiotensin-converting enzyme activity in 2K-1C rats. Left ventricular (LV) dysfunction and remodelling in 2K-1C rats were alleviated in the nobiletin-treated group (P < 0.05). Nobiletin reduced the upregulation of Ang II type I receptor (AT1R)/JAK (Janus kinase)/STAT (signal transducer and activator of transcription) protein expression in cardiac tissue of 2K-1C rats (P < 0.05). The reduction in kidney function, and accumulation of renal fibrosis in 2K-1C rats were alleviated by nobiletin (P < 0.05). Overexpression of AT1R and NADPH oxidase 4 (Nox4) protein in nonclipped kidney tissue was suppressed in the nobiletin-treated group (P < 0.05). The elevations in oxidative stress parameters and the reductions in antioxidant enzymes were attenuated in 2K-1C rats treated with nobiletin (P < 0.05). In summary, nobiletin had renin-angiotensin system inhibitory and antioxidant effects and attenuated LV dysfunction and remodelling via restoration of the AT1R/JAK/STAT pathway. Nobiletin also resolved renal damage that was related to modulation of the AT1R/Nox4 cascade in 2K-1C hypertension.

Genistein alleviates renin-angiotensin system mediated vascular and kidney alterations in renovascular hypertensive rats.

Genistein is a bioflavonoid mainly found in soybean. This study evaluated the effect of genistein on vascular dysfunction and kidney damage in two-kidney, one-clipped (2K1C) hypertensive rats. Male Sprague-Dawley-2K1C hypertensive rats were treated with genistein (40 or 80 mg/kg) or losartan 10 mg/kg (n = 8/group). Genistein reduced blood pressure, attenuated the increase in sympathetic nerve-mediated contractile response and endothelial dysfunction in the mesenteric vascular beds and aorta of 2K1C rats. Increases in the intensity of tyrosine hydroxylase (TH) in the mesentery and plasma norepinephrine (NE) were alleviated in the genistein-treated group. Genistein also improved renal dysfunction, hypertrophy of the non-clipped kidney (NCK) and atrophy of the clipped kidney (CK) in 2K1C rats. Upregulation of angiotensin II receptor type I (AT1R), nicotinamide adenine dinucleotide phosphate (NADPH) oxidase subunit 4 (Nox4) and Bcl2-associated X protein (BAX) and downregulation of B-cell lymphoma 2 (Bcl2) protein found in CK were restored by genistein. It also suppressed the overexpression of AT1R, transforming growth factor beta I (TGF-ß1), smad2/3 and p-smad3 in NCK. Genistein reduced serum angiotensin converting enzyme (ACE) activity and plasma angiotensin II (Ang II) in 2K1C rats. Low levels of catalase activity as well as high levels of superoxide generation and malondialdehyde (MDA) in 2K1C rats were restored by genistein treatment. In conclusion, genistein suppressed renin-angiotensin system-mediated sympathetic activation and oxidative stress in 2K1C rats. It alleviated renal atrophy in CK via modulation of AT1R/NADPH oxidase/Bcl-2/BAX pathways and hypertrophy in NCK via AT1R/TGF-ß1/smad-dependent signalling pathways.

A scan for genetic determinants of human hair morphology: EDAR is associated with Asian hair thickness.

Hair morphology is one of the most differentiated traits among human populations. However, genetic backgrounds of hair morphological differences among populations have not been clarified yet. In addition, little is known about the evolutionary forces that have acted on hair morphology. To identify hair morphology-determining genes, the levels of local genetic differentiation in 170 genes that are related to hair morphogenesis were evaluated by using data from the International HapMap project. Among highly differentiated genes, ectodysplasin A receptor (EDAR) harboring an Asian-specific non-synonymous single nucleotide polymorphism (1540T/C, 370Val/Ala) was identified as a strong candidate. Association studies between genotypes and hair morphology revealed that the Asian-specific 1540C allele is associated with increase in hair thickness. Reporter gene assays suggested that 1540T/C affects the activity of the downstream transcription factor NF-kappaB. It was inferred from geographic distribution of 1540T/C and the long-range haplotype test that 1540C arose after the divergence of Asians from Europeans and its frequency has rapidly increased in East Asian populations. These findings lead us to conclude that EDAR is a major genetic determinant of Asian hair thickness and the 1540C allele spread through Asian populations due to recent positive selection.

Epstein-Barr virus strains defined by the latent membrane protein 1 sequence characterize Thai ethnic groups.

Epstein-Barr virus (EBV) is ubiquitous in the human population and seroepidemiological studies have revealed that more than 90% of adults are infected with the virus in Thailand. It has been suggested that latent membrane protein 1 (LMP1) variants may differ in their tumorigenicity and geographical localization. The distribution of LMP1 variants of EBV in the Thai population was studied. A total of 259 LMP1 sequences from ten Thai ethnic groups (Lahu, Lisu, Shan, Red Karen, White Karen, Hmong, Akha, Mlabri, Moken and Urak Lawoi) were studied using direct PCR sequencing. Nucleotide sequences corresponding to the C terminus of the LMP1, including previously published sequences from central and southern Thais, were used in the phylogenetic analysis. Five strains--the B95-8 prototype, China 1, China 2, Mediterranean (Med) and SEA 2--were identified in ethnic groups in Thailand. The major strain and the distribution pattern differed by group and location. When the ethnic groups were classified by linguistic group, the prevalence of the SEA 2 strain was significantly different between Austro-Thais and other linguistic groups (P=0.0001), whereas, among Tibeto-Burman linguistic groups, the prevalence of the Med strain was different between matrilocal and patrilocal groups (P=0.0245). The distribution of LMP1 strains in ethnic minorities in Thailand is associated with ethnogeographical factors and the social/marriage system. This study thus provides evidence for the importance of interactions between populations in virus diversity.

TP53 codon 72 polymorphism and cervical cancer: a pooled analysis of individual data from 49 studies.

BACKGROUND: Cervical cancer is caused primarily by human papillomaviruses (HPV). The polymorphism rs1042522 at codon 72 of the TP53 tumour-suppressor gene has been investigated as a genetic cofactor. More than 80 studies were done between 1998 and 2006, after it was initially reported that women who are homozygous for the arginine allele had a risk for cervical cancer seven times higher than women who were heterozygous for the allele. However, results have been inconsistent. Here we analyse pooled data from 49 studies to determine whether there is an association between TP53 codon 72 polymorphism and cervical cancer. METHODS: Individual data on 7946 cases and 7888 controls from 49 different studies worldwide were reanalysed. Odds ratios (OR) were estimated using logistic regression, stratifying by study and ethnic origin. Subgroup analyses were done for infection with HPV, ethnic origin, Hardy-Weinberg equilibrium, study quality, and the material used to determine TP53 genotype. FINDINGS: The pooled estimates (OR) for invasive cervical cancer were 1.22 (95% CI 1.08-1.39) for arginine homozygotes compared with heterozygotes, and 1.13 (0.94-1.35) for arginine homozygotes versus proline homozygotes. Subgroup analyses showed significant excess risks only in studies where controls were not in Hardy-Weinberg equilibrium (1.71 [1.21-2.42] for arginine homozygotes compared with heterozygotes), in non-epidemiological studies (1.35 [1.15-1.58] for arginine homozygotes compared with heterozygotes), and in studies where TP53 genotype was determined from tumour tissue (1.39 [1.13-1.73] for arginine homozygotes compared with heterozygotes). Null results were noted in studies with sound epidemiological design and conduct (1.06 [0.87-1.29] for arginine homozygotes compared with heterozygotes), and studies in which TP53 genotype was determined from white blood cells (1.06 [0.87-1.29] for arginine homozygotes compared with heterozygotes). INTERPRETATION: Subgroup analyses indicated that excess risks were most likely not due to clinical or biological factors, but to errors in study methods. No association was found between cervical cancer and TP53 codon 72 polymorphism when the analysis was restricted to methodologically sound studies. FUNDING: German Research Foundation (DFG).

Genetic Polymorphisms of Vitamin D Receptor Gene are Associated with Cervical Cancer Risk in Northeastern Thailand.

OBJECTIVE: This study aimed to explore whether VDR polymorphisms (Fok1, Apa1 and Taq1) are associated to the cervical cancer in Thai population. MATERIALS AND METHODS: Subjects of 204 cervical cancer patient and 204 age-matched healthy control were enrolled in the case-control study. VDR polymorphisms were detected by using real-time PCR. Haplotype analysis of three loci was applied to the obtained genotypes. RESULTS: Significantly increased risk for cervical cancer was observed in carriers of TT genotype (p = 0.0388) and T allele (p = 0.0357) of Fok1 and TC genotype (p = 0.0001), CC genotype (p = 0.0160) and the C allele of Taq1 (p = 0.0001). Haplotype analyses revealed a significant correlation between C-T-C, T-G-C and T-T-C haplotypes and elevated risk for cervical cancer (OR = 2.06; 95%CI = 1.06-4.00; p = 0.0313, OR = 2.15; 95%CI = 1.22-3.80; p = 0.0078 and OR = 2.81; 95%CI = 1.53-5.16; p = 0.0006, respectively). Furthermore, haplotype carrying C allele of Taq1 (C-G-C + C-T-C + T-G-C + T-T-C) significantly increased cervical cancer risk with OR of 1.92 (95%CI = 1.32-2.79, p = 0.0006). CONCLUSION: Our finding revealed an association between VDR polymorphisms and cervical cancer risk. Taq1 C allele might be a molecular marker for cervical cancer development.
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FGFR2 is associated with hair thickness in Asian populations.

Hair morphology is one of the most differentiated traits among human populations. A previous study has shown that a nonsynonymous single nucleotide polymorphism (SNP) in the EDAR gene, EDAR 1540T/C, is strongly associated with hair thickness in Asian populations. However, the contributions of other genes remain to be elucidated. In this study, 12 SNPs on 10 hair formation-related genes with high differentiation between Asian and other populations were examined to further identify genes associated with hair morphology. A multiple regression analysis adjusted for age, sex, population and the effect of EDAR 1540T/C revealed an SNP in intron 9 of FGFR2, rs4752566, to be significantly associated with hair thickness (cross-sectional area; P-value=0.0052, small diameter; P-value=0.029 and large diameter; P-value=0.0015). In the genomic region containing the FGFR2 gene, rs4752566 was not in strong linkage disequilibrium (LD) with the surrounding SNPs, indicating that the significant association of rs4752566 with the hair thickness is not due to LD with polymorphisms of the other genes. The rs4752566-T allele of FGFR2, associated with thicker hair, was also shown to be associated with higher mRNA level of FGFR2 (P-value=0.0270). These results suggest that the FGFR2 polymorphism affects the variation in hair thickness in Asia through alteration in the expression level of FGFR2.

Recent origin and cultural reversion of a hunter-gatherer group.

Contemporary hunter-gatherer groups are often thought to serve as models of an ancient lifestyle that was typical of human populations prior to the development of agriculture. Patterns of genetic variation in hunter-gatherer groups such as the Kung and African Pygmies are consistent with this view, as they exhibit low genetic diversity coupled with high frequencies of divergent mtDNA types not found in surrounding agricultural groups, suggesting long-term isolation and small population sizes. We report here genetic evidence concerning the origins of the Mlabri, an enigmatic hunter-gatherer group from northern Thailand. The Mlabri have no mtDNA diversity, and the genetic diversity at Y-chromosome and autosomal loci are also extraordinarily reduced in the Mlabri. Genetic, linguistic, and cultural data all suggest that the Mlabri were recently founded, 500-800 y ago, from a very small number of individuals. Moreover, the Mlabri appear to have originated from an agricultural group and then adopted a hunting-gathering subsistence mode. This example of cultural reversion from agriculture to a hunting-gathering lifestyle indicates that contemporary hunter-gatherer groups do not necessarily reflect a pre-agricultural lifestyle.

Genetic Polymorphism of the Glutathione S-transferase Pi 1 (GSTP1) and Susceptibility to Cervical Cancer in Human Papilloma Virus Infected Northeastern Thai Women

Objective: We aimed to investigate any association between a genetic polymorphism of the detoxification GSTP1 gene and risk of cervical cancer in northeastern Thailand. Materials and Methods: Genotyping of GSTP1 was performed for 198 squamous cell cervical cancer (SCCA) patients and 198 age-matched healthy controls with the PCR-RFLP method. Results: The respective frequencies of the G allele were 0.33 and 0.26 in the controls and cases, the difference being significant (OR = 0.69 [95% CI: 0.50-0.95, p=0.0192]). Among women infected with high-risk types of HPV, being a heterozygous carrier was associated with a reduced risk of cervical cancer (adjusted OR = 0.32 [95% CI: 0.12-0.91, p=0.031]). Similarly, a decreased risk was observed in heterozygous women with a non-smoking partner (adjusted OR = 0.27 [95% CI: 0.09-0.83, p=0.023]). Conclusions: GSTP1 polymorphism could influence susceptibility to cervical cancer among northeast Thai women; either as a independent factor or in combination with high-risk HPV infection. Dual-testing of HPV and the GSTP1 might prove an effective screening tool for cervical cancer.

Haplotype Analysis of MDR1 and Risk for Cervical Cancer in Northeastern Thailand

Objective: The aim of this study was to investigate the association between genotype and haplotype of MDR1 (C1236T, G2677T/A and C3435T) and the risk for cervical cancer in Northeastern Thai women. Methods: An age-matched case-control study involving squamous cell cervical cancer (SCCA) patients (n=204) and healthy controls (n=204) was enrolled for MDR1 genotyping by real-time PCR method. Results: The genotype distribution of MDR1 in both patients and controls was not significantly different (p>0.05). The haplotype analysis showed that T-T-T was the most common haplotype in this population. Significantly increased risk of cervical cancer was observed in carriers of T-T-C and C-G-T haplotypes with ORs of 1.86 (95%CI=1.02-3.39, p=0.0416) and 2.00 (95%CI=1.18-3.40, p=0.0140), respectively. Analysis of 2677-3435 haplotype showed increased risk for cervical cancer in G-T (OR=1.55; 95% CI=1.12-2.13, p=0.0432) and T-C (OR=1.91; 95%CI=1.05-3.47, p=0.0325). Conclusion: The results provide evidence that haplotype of MDR1 may be an important risk factor for cervical cancer development in Northeastern Thai women.

Analysis of LMP1 variants of EBV in Southern Thailand: evidence for strain-associated T-cell tropism and pathogenicity.

BACKGROUND: The latent membrane protein 1 (LMP1) of Epstein-Barr virus (EBV) has sequence heterogeneity. Some of the variants are associated with altered tumorigenic activity and show geographically specific localization. In Thailand, the EBV genome is frequently detected in circulating T cells of T-cell diseases. OBJECTIVE: To determine the role of EBV LMP1 variation in the genesis of T-cell diseases, we focused on virus factors and analyzed EBV strains in Thailand. STUDY DESIGN: EBV DNA was extracted from 18 healthy individuals and 45 patients with T-cell diseases in Southern Thailand and 30 healthy individuals in Central Thailand. By using PCR-direct sequencing method, nucleotide sequences corresponding to the carboxyl terminus of the LMP1 were determined. RESULTS: Four known strains, B95-8 prototype, China 1, China 2 and Mediterranean (Med) and two novel strains, Southeast Asia 1 (SEA 1) and Southeast Asia 2 (SEA 2) were identified. The prevalence of China 2 strain was significantly different (p=0.006) between Central and Southern Thailand. Higher prevalence (p=0.026) of 30-bp deletion type in the Southern Thais was observed. The LMP1 Med strain was associated with the worse prognosis (p=0.029). Among T-cell diseases patients, CD3(+)-cell oriented infection was recognized in SEA1 strain (p=0.025). CONCLUSION: The distribution of EBV strains may be associated with geographic/ethnic and clinical background in the Thai population. Certain EBV strains defined by their LMP1 sequence may influence cell tropism, disease association, or disease severity.

Selected risk factors, human papillomavirus infection and the p53 codon 72 polymorphism in patients with squamous intraepithelial lesions in northeastern Thailand.

Risk factors for cervical squamous intraepithelial lesions (SIL) including human papillomavirus (HPV) infection and the p53 codon 72 polymorphism were investigated in a case-control study with 103 cases and 105 controls in Northeastern Thailand. Increased risk for SIL was observed for age at menarche (odds ratio (OR) = 2.2; p< 0.005), age at the first sexual intercourse (OR=2.4; p< 0.05), number of sexual partners (OR=2.7; p< 0.005) and partners' smoking history (OR=2.3-3.2; p< 0.01). Prevalence of malignant type of HPV infection in the control and SIL groups was 18.1% and 60.2%, respectively. HPV infection significantly increased risk for SIL 6.8-fold (p< 0.001). HPV-16 infection was the commonest (31 out of 62 carriers) in SIL patients and highly associated with risk. The p53 codon 72 polymorphism was not identified as a genetic risk for SIL in this study, as demonstrated in Thai cervical cancer. Therefore, to prevent cervical neoplasia or HPV infection, inclusion of knowledge on sexual behavior and effects of smoking into public health programs is important and, at the same time, a nation-wide screening scheme for cervical abnormalities including HPV-typing is a high priority in Thailand.

Preliminary Study of the GSTM1 Null Polymorphism and History of Tobacco Smoking among Oral Cancer Patients in Northeastern Thailand.

Risks with GSTM1 genotypes and potential roles of smoking in the susceptibility to oral squamous cell carcinoma (OSCC) were studied in Northeastern Thailand. Study subjects were 79 histologically-confirmed OSCC cases (31 men, 48 women) and 79 age- and sex-matched healthy controls ranging in age from 25 to 84 years. GSTM1 genotyping was achieved by two independent PCR assays. The GSTM1 null allele and the homozygous genotype did not increase risk of OSCC vs the wild type allele and the remaining genotypes. When the focus was on the smoking habit, male subjects who smoked ≥10 or ≥35 years were at significantly increased risk for OSCC with adjusted ORs of 4.88 [95%CI, 1.41-16.87, p=0.012] or 4.94 [95%CI, 1.62-15.12, p=0.005], respectively. A higher risk for OSCC was found for smoking amount; those who smoked >5 or >10 pack-years were at a higher risk with adjusted OR of 4.46 [95%CI; 1.45-13.74, p=0.009] or 3.89 [95%CI; 1.34-11.28, p=0.012], respectively. There are certain smoking patterns that give greater risks and thus both smoking duration and pack-years should be taken into consideration in tobacco related cancer prevention.

Lack of participation of the GSTM1 polymorphism in cervical cancer development in Northeast Thailand.

The potential association between the GSTM1 deletion polymorphism and risk of cervical cancer was investigated in Northeastern Thailand. DNA was extracted from buffy coat specimens of 198 patients with squamous cell carcinoma of the cervix and 198 age-matched healthy controls. Genotyping of the GSTM1 was conducted by using two PCR methods, a short- and a long-PCR. Distribution of the GSTM1 genotypes in between the cases and the controls was not significantly different (p>0.5 by χ2 test). The results suggest that the GSTM1 deletion polymorphism is not a risk factor for squamous cell carcinoma of the cervix in the northeast Thai women.

Contribution of epigenetic risk factors but not p53 codon 72 polymorphism to the development of cervical cancer in Northeastern Thailand.

Relationships between cervical cancer and risk factors were investigated in Northeastern Thailand. Cases (n = 90) with squamous cell cervical cancer (SCCA) and age matched healthy controls (n = 100) were recruited. The p53 codon 72 polymorphism, proline and arginine allele, was studied by the polymerase chain reaction-restriction fragment length polymorphism. There was no significant difference in the allele and the genotype distribution between the SCCA and the control groups (P > 0.05). Significant difference was observed in the number of sexual partners (P < 0.003) age at the first sexual intercourse (P < 0.03) and number of parities ( P< 0.006). After adjusted by age and p53 genotype, significant difference was still observed in the number of sexual partners (P = 0.017) The partners' smoking increased the risk to develop SCCA. Increased odds ratios were observed when the partner had smoking history both at present (3.31; P < 0.003) and in the past (3.36; P < 0.003). The p53 polymorphism itself may not be a risk factor for cervical cancer in Northeastern Thailand. Much attention should be paid to the presence of other risk factors such as sexual behaviors and smoking habits in the prevention of cervical cancer in this region.