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Jingwen Wang, Jing Jiang,
Yang Zhao,
Vendhan Gajalakshmi,
Kiyonori Kuriki,
Sadao Suzuki,
Teruo Nagaya,
Seiichi Nakamura,
Susumu Akasaka,
Hideki Ishikawa,
Shinkan Tokudome
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ABSTRACT: Susceptibility to sporadic colorectal cancer is multifactorial and arises from interactive combinations of allelic variants in low-penetrance genes and relevant environmental risk factors. Genetic polymorphisms in metabolic enzymes as gene susceptibility factors may modify colorectal cancer risk. We evaluated the risk of colorectal cancer associated with respective or combined glutathione S-transferase (GST) polymorphisms and assessed the interactions between genes and environmental factors in a case-control study in an Indian population.
The study included 59 colon and 243 rectal cancer cases, and 291 cancer-free healthy controls. GST genotypes were detected by multiplex PCR-based and PCR-RFLP methods. The risk of cancer associated with GST polymorphisms was estimated by calculation of odds ratios (ORs) and confidence intervals (95% CIs) using unconditional logistic regression.
The GSTM1 null genotype was found to be associated with a significantly increased rectal cancer risk (OR=1.55; 95% CI, 1.05-2.30), while the GSTT1 null genotype with a greater risk of colon cancer (OR=2.15; 95% CI, 1.04-4.32). A substantial increase of both colon (OR=10.81; 95% CI, 1.11-107.22) and rectal (OR=4.80; 95% CI, 0.94-35.91) cancer risk was shown for the combination of GSTM1 null, GSTT1 null and GSTP1 105Val allele. The combined GSTM1 null and GSTP1 114Val allele also revealed an increased risk for either colon cancer (OR=4.69; 95% CI, 0.84-23.87) or rectal cancer (OR=5.68; 95% CI, 1.79-22.16). Furthermore, the combination of GSTM1 null, GSTT1 null and GSTP1 114Val allele was found in 2 rectal cancer cases.
Our results suggest that co-exist of GSTM1 null, GSTT1 null and the variant GSTP1 105Val or 114Val allele may be predisposing risk factors for colorectal cancer in Indian population.
Cancer epidemiology. 02/2011; 35(1):66-72.
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Jingwen Wang,
Yang Zhao, Jing Jiang,
Vendhan Gajalakshmi,
Kiyonori Kuriki,
Seiichi Nakamura,
Susumu Akasaka,
Hideki Ishikawa,
Sadao Suzuki,
Teruo Nagaya,
Shinkan Tokudome
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ABSTRACT: Genetic polymorphisms in DNA repair genes may influence variations in individual DNA repair capacity, which could be associated with the development of cancer. We detected the distributions of three single-nucleotide polymorphisms (XRCC1 Arg399Gln, XRCC3 Thr241Met and XPD Lys751Gln) in DNA repair genes, and assessed the associations of these genetic polymorphisms with colon and rectal cancer susceptibility as well as evaluated the interactions of gene-gene and gene-environment in a case-control study of an Indian population.
This case-control study was conducted with 302 cases (including 59 colon and 243 rectal cancer patients) and 291 cancer-free healthy controls. Genotypes were determined by PCR-RLFP assays. The effects [odds ratios (ORs) and 95% confidence intervals (95% CIs)] of genetic polymorphisms on colorectal cancer were estimated using unconditional logistic regression.
The XRCC1 399Gln allele was found to be associated with a significantly increased rectal cancer risk among men (OR = 1.65, 95% CI 1.04-2.64). Whereas the XRCC3 241Met allele showed a protective tendency against rectal cancer (OR = 0.68, 95% CI 0.46-1.02) for both men and women. Furthermore, a combination of the XRCC1 399Gln allele with XRCC3 Thr/Thr genotype and the XPD 751Gln allele demonstrated the highest rectal cancer risk (OR = 3.52, 95% CI 1.43-9.44).
The combined effects of putative risk alleles/genotypes for different DNA repair pathways may strengthen the susceptibility to rectal cancer.
Journal of Cancer Research and Clinical Oncology 03/2010; 136(10):1517-25. · 2.56 Impact Factor
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ABSTRACT: To investigate whether the common cyclin D1 (CCND1) A870G polymorphism is a risk factor for colorectal cancer (CRC) in an Indian population.
In this study, 301 newly diagnosed CRC patients and 291 healthy control subjects were genotyped by the PCR-RFLP method. Genotype frequencies were compared between cases and controls, and the association of genotypes with CRC was studied.
The CCND1 870 A allele was more frequently observed in CRC patients than controls (0.63 vs. 0.56, P=0.01), and after adjustment for age, sex, smoking habits, family history, family income and the consumption of meat, fish, vegetables and fruit, an increased risk was observed for the AA genotype compared to the GG+AG genotype (OR=1.56; 95% CI: 1.10-2.21). The increased risk were also found for colon (OR=1.96; 95% CI: 1.08-3.57) and rectal cancer (OR=1.51; 95% CI: 1.04-2.19). No correlation was observed between genotypes and age of diagnosis of CRC (49.9, 48.7 and 49.4 years for the GG, AG and AA genotypes, respectively; P=0.84). Multivariate analysis also revealed a stronger positive association with the AA genotype among patients with high meat intake (OR=2.67; 95% CI: 1.29-5.51), and particularly significant inverse associations with the GG+AG genotypes were also found for those with high vegetable consumption (OR=0.46; 95% CI: 0.27-0.79 of 2-3 servings/day, and OR=0.31; 95% CI: 0.18-0.53 for >3 servings/day) and fish intake (OR=0.48; 95% CI: 0.28-0.82).
These data support the hypothesis that the CCND1 A870G polymorphism may increase the risk of CRC in our Indian population.
Journal of Cancer Research and Clinical Oncology 03/2006; 132(3):193-9. · 2.56 Impact Factor
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ABSTRACT: Although the incidence rate of colorectal cancer is very low, and rectal cancer remains more common in India, a significant increase in its incidence has been reported for both men and women over the last 2 decades. We evaluated MTHFR genetic susceptibility and common environmental risk factors in the development of colon and rectal cancer, and assessed the interactions between gene and environmental factors with colorectal cancer in a case-control study in the Indian population. The study included 59 colon cancer cases, 243 rectal cancer cases and 291 controls. The variant MTHFR 677T allele is rare, while the 1298C allele is common among Indians. MTHFR 677T showed no association with colon cancer (OR = 0.82; 95% CI 0.28-2.05) and a nonstatistically significantly elevated risk with rectal cancer (OR = 1.51; 95% CI 0.86-2.68), and MTHFR 1298 CC genotype was found to be associated with a significantly decreased risk for both colon cancer (OR = 0.30, 95% CI 0.09-0.81) and rectal cancer (OR = 0.43, 95% CI 0.23-0.80). High intake of nonfried vegetables or fruits was inversely associated with both colon and rectal cancer risk. Especially, the combination of a high intake of nonfried vegetables and MTHFR 1298CC genotype was associated with the lowest rectal cancer risk (OR = 0.22, 95% CI 0.09-0.52). Regarding alcohol consumption, indigenous Indian alcohol drinkers (OR = 2.26, 95% CI 0.86-6.36), and those consuming alcohol for duration more than 20 years (OR = 1.55, 95% CI 0.73-3.33), were at a somewhat higher rectal cancer risk. Moreover, the consumed alcohol amount (gram-years) may be also associated with colon or rectal cancer risk.
International Journal of Cancer 03/2006; 118(4):991-7. · 5.44 Impact Factor
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ABSTRACT: The aim of the present study was to investigate associations between Pro12Ala and C161T polymorphisms in the peroxisome proliferator-activated receptor-gamma (PPAR-gamma) gene and colorectal cancer (CRC) risk. We recruited 301 newly diagnosed CRC patients and 291 healthy control subjects at the Madras Cancer Institute in Chennai, India, from 1999 to 2001. Genotypes of the Pro12Ala and C161T polymorphisms were determined using the PCR-RFLP method. After adjustment for age, sex, smoking habit, family history and family income, an increased risk of CRC was observed for the C/T + T/T genotype compared to the C/C genotype of the C161T polymorphism (odds ratio = 1.61, 95% confidence interval: 1.10-2.36), whereas no significant association was found for Pro12Ala (odds ratio = 1.06, 95% confidence interval: 0.70-1.61). Analysis with estimated haplotypes showed a significant difference in haplotype frequencies between cases and controls (chi(2) = 11.62, P = 0.009, d.f. = 3). The relationship between the two polymorphisms and CRC risk was not significantly modified by dietary intake of fish. Although the biological mechanisms of the observed association remain to be elucidated, our findings suggest that the C161T polymorphism of the PPAR-gamma gene is related to risk of CRC. Further research is needed to investigate functional implications of polymorphisms of the PPAR-gamma gene in CRC development.
Cancer Science 09/2005; 96(8):507-12. · 3.33 Impact Factor
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Jing Jiang,
Sadao Suzuki,
Jin Xiang,
Kiyonori Kuriki,
Akihiro Hosono,
Kazuyuki Arakawa,
Jingwen Wang,
Teruo Nagaya,
Masayo Kojima,
Nobuyuki Katsuda,
Shinkan Tokudome
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ABSTRACT: To investigate associations between plasma carotenoids, alpha-tocopherol and retinol with colorectal adenomas risk, we measured concentrations in 224 asymptomatic colorectal adenoma cases and 230 population-based controls matched for age and sex. After adjustment for age, history of colorectal adenomas and cancers, BMI, smoking, drinking status, multivitamin consumption and plasma total cholesterol, the risk of colorectal adenomas in the highest quartile was approximately half of that of men in the lowest quartile for alpha-carotene (OR=0.38; 95% CI: 0.18-0.84; P(trend)=0.01), beta-carotene (OR=0.51; 95% CI: 0.24-1.07; P(trend)=0.03) and total carotenoids (OR=0.48; 95% CI: 0.22-1.03; P(trend)=0.04). In addition, a protective association for alpha-carotene in women was also indicated, but which did not reach statistical significance (OR=0.53; 95% CI: 0.19-1.52; P(trend)=0.35). Our findings suggest a protective effect of carotenoids against the development of colorectal adenomas.
Cancer Letters 09/2005; 226(2):133-41. · 4.24 Impact Factor
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Jingwen Wang,
Yifu Deng,
Li Li,
Kiyonori Kuriki,
Jianmin Ding,
Xiaochun Pan,
Xin Zhuge, Jing Jiang,
Chenhong Luo,
Peng Lin,
Shinkan Tokudome
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ABSTRACT: A case-control study of 164 lung adenocarcinoma (AC) patients with 181 age- and gender-matched healthy controls was conducted in order to assess any associations between glutathione-S-transferase M1 (GSTM1), cytochrome P4501A1 (CYP1A1) and cyto-chrome P4502E1 (CYP2E1) polymorphisms and susceptibility to lung AC in Chinese. The presence of CYP2E1 variant allele was significantly less frequent in cases than in controls, while the distribution of GSTM1 null genotype and variant CYP1A1 Msp1 allele did not vary between cases and controls. After adjustment for age, gender, smoking and all other genotypes, the CYP2E1 Rsa1 variant allele was significantly associated with decreased risk of lung AC [odds ratio 0.534 (95% confidence interval, 0.340–0.837)]. Furthermore, 3.0-fold increased risk was found in individuals with combined GSTM1 null genotype and CYP2E1 Rsa1 wild type versus those with combined GSTM1 non-null type and CYP2E1 variant allele. Our results suggest that CYP2E1 Rsa1 variant allele is associated with a decreased risk of lung AC, and combined GSTM1 null genotype and CYP2E1 Rsa1 wild type has a promoting effect on susceptibility to lung AC. (Cancer Sci 2003; 94: 448–452)
Cancer Science 08/2005; 94(5):448 - 452. · 3.33 Impact Factor
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Jingwen Wang,
Yifu Deng,
Li Li,
Kiyonori Kuriki,
Jianmin Ding,
Xiaochun Pan,
Xin Zhuge, Jing Jiang,
Chenhong Luo,
Peng Lin,
Shinkan Tokudome
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[hide abstract]
ABSTRACT: A case-control study of 164 lung adenocarcinoma (AC) patients with 181 age- and gender-matched healthy controls was conducted in order to assess any associations between glutathione-S-transferase M1 (GSTM1), cytochrome P4501A1 (CYP1A1) and cytochrome P4502E1 (CYP2E1) polymorphisms and susceptibility to lung AC in Chinese. The presence of CYP2E1 variant allele was significantly less frequent in cases than in controls, while the distribution of GSTM1 null genotype and variant CYP1A1 Msp1 allele did not vary between cases and controls. After adjustment for age, gender, smoking and all other genotypes, the CYP2E1 Rsa1 variant allele was significantly associated with decreased risk of lung AC [odds ratio 0.534 (95% confidence interval, 0.340-0.837)]. Furthermore, 3.0-fold increased risk was found in individuals with combined GSTM1 null genotype and CYP2E1 Rsa1 wild type versus those with combined GSTM1 non-null type and CYP2E1 variant allele. Our results suggest that CYP2E1 Rsa1 variant allele is associated with a decreased risk of lung AC, and combined GSTM1 null genotype and CYP2E1 Rsa1 wild type has a promoting effect on susceptibility to lung AC.
Cancer Science 06/2003; 94(5):448-52. · 3.33 Impact Factor
