MTHFR polymorphisms, dietary folate intake and risks to breast cancer / 中华预防医学杂志

<p><b>OBJECTIVE</b>To evaluate the relationship between dietary folate intake and genetic polymorphisms of 5, 10-methylenetetrahydrofolate reductase (MTHFR) with reference to breast cancer risk.</p><p><b>METHODS</b>A case-control study was conducted with 669 cases and 682 population-based controls in Jiangsu province of China. MTHFR C677T and A1298C genotypes were identified by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) methods. Dietary folate intake was assessed by using an 83-item food frequency questionnaire. Odds ratios (OR) were estimated with an unconditional logistic model.</p><p><b>RESULTS</b>The frequencies of MTHFR C677T C/C, C/T and T/T genotypes were 32.37% (202/624), 48.88% (305/624) and 18.75% (117/624) in cases and 37.66% (235/624), 48.24% (301/624) and 14. 10% (88/624) in controls, respectively. The difference in distribution was significant (chi2 = 6.616, P = 0.037), the T/T genotype being associated with an elevated OR for breast cancer (1.62, 95% CI: 1.14 -2.30). The frequencies of MTHFR A1298C A/A, A/C and C/C were 71.47% (446/624), 27.08% (169/624) and 1.44% (9/624) in cases and 68.11%(425/624), 30.13% (188/624) and 1.76% (11/624)in controls,with no significant differences found (chi2 = 1.716, P= 0.424). Folate intake of cases [(263.00 +/- 137.38) microg/d] was significantly lower than that of controls [(285.12 +/- 149.61) microg/d] (t = -2. 830, P =0.005). Compared with the lowest tertile (< or = 199.08 microg/d) of folate intake, the adjusted OR for breast cancer in the top tertile (> or = 315.11 microg/d) was 0.70 (95% CI: 0.53 -0.92). Among individuals with the MTHFR A1298C A/A genotype,adjusted OR for breast cancer were 0.89 (95% CI: 0.62 - 1.27) and 1.69 (95% CI: 1.20 - 2.36) for the second to the third tertile of folate intake compared with the highest folate intake group (X2trend = 11.372, P = 0.001).</p><p><b>CONCLUSION</b>The findings of the present study suggest that MTHFR genetic polymorphisms,and dietary intake of folate may modify susceptibility to breast cancer.</p>

Genetic polymorphisms of methylenetetrahydrofolate reductase and susceptibility to colorectal cancer.

OBJECTIVES: To study the relation between genetic polymorphisms of methylenetetrahydrofolate reductase (MTHFR) C677T or A1298C and the susceptibility of colorectal cancer. METHODS: We conducted a case-control study with 315 cases of colorectal cancer and 371 population-based controls in Jiangsu province, China. The epidemiological data were collected, and DNA of peripheral blood leukocytes was obtained from all of the subjects. MTHFR C677T and A1298C genotypes were detected by the PCR-RFLP method. RESULTS: (1) When men and women were assessed together, the frequencies of the MTHFR C677T and A1298 genotypes or their alleles were not significantly different between controls and colon cancer or rectal cancer cases. No significant relation was observed between MTHFR C677T or A1298C polymorphisms and colon or rectal cancer susceptibility. (2) Among males, individuals who had MTHFR C677T T/T genotype were at a significantly higher risk of developing colon cancer (age-, residence-, smoking-, alcohol drinking-, tea consumption-adjusted OR=2.15, 95%CI: 1.07-4.33) compared with those who had C677T C allele. Individuals who had C677T T/T and A1298C A/A genotypes were at an increased risk of developing colon cancer (adjusted OR=2.64, 95%CI: 1.20-5.81) compared with those with C677T C allele and A1298C A/A genotypes among males. On the contrary, individuals who had C677T T/T and A1298C A/A genotypes were at an decreased risk of developing rectal cancer (adjusted OR=0.47, 95%CI: 0.22-1.03). CONCLUSIONS: These results in the present study suggested that polymorphisms of the MTHFR C677T could influence susceptibility to colon or rectal cancer and that there was a coordinated effect between MTHFR A1298C A/A and C677T T/T genotypes among males.

Aberrant promoter methylation profile in pleural fluid DNA and clinicopathological factors in patients with non-small cell lung cancer.

The aim of this study was to investigate the prognostic value of hypermethylation of tumor suppressor genes in patients with non-small cell lung cancer (NSCLC). In samples from 34 lung patients with malignant pleural effusions, we used a methylation-specific polymerase chain reaction to detect aberrant hypermethylation of the promoters of the DNA repair gene O6-methylguanine-DNA methyltransferase (MGMT), p16INK4a, ras association domain family 1A (RASSF1A), apoptosis-related genes, death-associated protein kinase (DAPK), and retinoic acid receptor beta(RARbeta).There is no association between methylation status of five tumor suppressor genes including MGMT, p16INK4a, RASSF1A, DAPK and RARbeta in pleural fluid DNA and clinicopathological parameters including clinical outcome. Aberrant promoter methylation of tumor suppressor genes in pleural fluid DNA could not be a valuable prognostic marker of NSCLC patients with malignant pleural effusion.

The increasing incidence of colorectal cancer and the preventive strategy in Japan.

BACKGROUND: In Japan, the westernization of lifestyle, especially dietary habits, has progressed remarkably since 1950 and is presumably directly related to the increasing incidence of colorectal cancer (CRC). The aim of this epidemiology note was to summarize the most recent trends in CRC incidence and predictions until 2020 for suggesting the preventive strategies in Japanese. METHODS: Using the newest published data in Japan, the most recent trends in CRC incidence and the predicted numbers of incident cases of CRC until 2020 were summarized. RESULTS: Dietary intake of milk, meat, eggs and fat/oil demonstrated remarkable increment through 1950 to 1970, and since then has remained relatively constant. Compared with values for 1975, age-adjusted incidence rates for colon and rectal cancers were estimated to be 3.7 and 1.9 times higher among men and 2.9 and 1.3 times higher among women by 1995 or 2000, respectively, and then to plateau. Considering progression of aging of the society, numbers of incident cases for colon cancer among men and women have been predicted to increase 9.5 and 7.5 times by 2005 and 12.3 and 10.5 times by 2020, respectively, from the 1975 baseline. Likewise, the figures for rectal cancer have been predicted to increase. CONCLUSION: The increment of CRC incidence is assumed to coincide with such changes in dietary intake after approximately 20-years lag. Concrete programs for lifestyle modification and more emphasis of early cancer screening are now needed for prevention purposes.

Overview of existing networks--is there a rationale for an Asian Cancer Registry Network?

Cancer registration is the base for our understanding of the burden of neoplastic disease in our populations at the local level. Comparability of data is essential for interpretation and this in turn depends on standardization of methodology and diagnostic and other criteria applied. If this is to be achieved across Asia, some form of international organization is clearly necessary. The question therefore should be whether the existing arrangement is adequate, and if this is not the case how a network in Asia might be established with due consideration of aims and attainable objectives. The present commentary focuses on the contributions made by the International Agency for Research on Cancer (IARC), the International Association of Cancer Registries (IACR), the European Network of Cancer Registries (ENCR), the North American Association of Central Cancer Registries (NAACCR) and individual country-based or region-based associations already active in Asia. An argument is presented here that there is a rationale for an Asian Network of Cancer Registries, working alongside and learning from the existing international organizations to promote effective cancer registration and disease prevention in Asia.

What do cancer registry and household expenditure data in Japan tell us about variation in tumour burden ?

Data from the total of six Japanese Cancer Registries presently reporting to Cancer Incidence in Five Continents demonstrate marked variation in relative prevalence of cancers at particular sites, despite the genetic homogeneity of the Japanese population. Thus either major differences in registry procedures or local environment must be playing an important role and since the variation is clearly changing with time, the former must be considered likely. Over the last 25 year period, incidence rates for the esophagus have been generally increasing in Japan, except in Miyagi where they have been persistently high. Stomach cancer rates are on the decrease, although the trend is not so clear in Yamagata and Hiroshima, while colon and rectal cancers have both demonstrated consistent increment throughout the period surveyed, with a remarkable correlation between the two sites evident on cross-registry comparisons. Continued increases have also been apparent in lung, kidney, urinary bladder and prostate cancers in males and in breast, endometrium and thyroid neoplasms in females. Cervical cancer, in contrast, is decreasing, although a plateau may now have been reached in Miyagi. In the hepatopancreatic axis, patterns have generally showed elevation followed by a recent reduction, although without correlations among liver, gallbladder and pancreas rates at the cross-registry level. Common lifestyle factors may to some extent underly the increases seen in colon, breast, urinary bladder and thyroid incidence rates, given the significant relations apparent for these in the latest data across registries. Whether analysis of variation in dietary intake and exposure to other risk factors, for example using data for household expenditure, may provide clues to explaining the variation apparent across Japan is a question warranting further consideration. If so an expanded role for the cancer registry could well be envisaged.

Reproducibility of a semi-quantitative food frequency questionnaire in Chaoshan area, China.

OBJECTIVE: To examine reproducibility of assessed intake of foods and nutrients according to a semi-quantitative food frequency questionnaire (SQFFQ) in adult doctors and nurses residing in Chaoshan area of China. SUBJECTS: The SQFFQ was administered first in October to December of 2004 to 120 adult doctors and nurses living in Chaoshan area of China and was then re-administered to 102 three months later between January and March of 2005 (SQFFQ 1 and SQFFQ 2). METHODS: Reproducibility was evaluated in terms of consumption of 10 food groups and energy and 34 macro- and micro-nutrients based on the SQFFQ from the 102 doctors and nurses. RESULTS: For intake of foods, Pearsom's correlation coefficients (CCs) with log-transformation and energy adjustment (minimum - median - maximum) range from 0.43 (eggs) - 0.84 - 0.90 (teas). Spearman's rank CCs with energy adjustment ranged from 0.77 (cereals) - 0.84 - 0.94 (milks). Kappa statistics with energy adjustment ranged from 0.53 (vegetables) - 0.63 - 0.82 (teas). For consumption of nutrients, Pearson's correlation coefficients (CCs) with log-transformation and energy adjustment (minimum - median - maximum) range from 0.83 (docosahexaenoic acid and oryzanin) - 0.88 - 0.90 (linolenic acid, vitamin A, folic acid, vitamin E, calcium, sodium, selenium and magnesium). Spearman's rank CCs with energy adjustment ranged from 0.81 (oryzanin and vitamin C) - 0.86 - 0.90 (sodium). Kappa statistics with energy adjustment ranged from 0.49 (protein) - 0.60 - 0.77 (sodium). CONCLUSION: Substantially high reproducibility was observed; it is possible to use the tailored, relatively simple, but comprehensive, self-administered SQFFQ to facilitate assessment of the association between lifestyle and health/disease in large-scale epidemiological studies.

Comparison of Japanese, American-Whites and African-Americans--pointers to risk factors to underlying distribution of tumours in the colorectum.

Relative incidence rates for colon and rectal cancer vary greatly between populations in the world. While Japanese have historically had low prevalence, immigration to the United States has now resulted in equal if not higher rates than in Caucasian- or African-Americans. Furthermore, recent data from some population-based registries in Japan itself are also pointing to particularly high susceptibility. Of particular interest is the fact that Japanese in both the home country and the US in fact have far higher rates for rectal cancer than the other two ethnic groups. An intriguing question is whether they might also demonstrate variation from Caucasian- and African-Americans in the relative incidence rates for proximal and distal colon cancers, given the clear differences in risk factors like diabetes, physical exercise, smoking, alcohol consumption, meat and fish intake and calcium exposure which have been shown to operate in these two sites. A comprehensive epidemiological research exercise is here proposed to elucidate ethnic variation in colorectal cancer development, based on cross-cancer registry descriptive and case control approaches. It is envisaged that additional emphasis on screened populations should further provide important insights into causal factors and how primary and secondary prevention efforts can be optimized.

Esophageal cancer risk by ALDH2 and ADH2 polymorphisms and alcohol consumption: exploration of gene-environment and gene-gene interactions.

Alcohol drinking is a major risk factor for esophageal cancer in Japan and its impact may be modulated by levels of ALDH2, ADH2 and CYP2E1, three representative alcohol-metabolizing enzymes which display genetic polymorphisms altering individual alcohol-oxidizing capacity and drinking behavior. To assess the actual influence of ADH2 Arg47His, ALDH2 Glu487Lys and CYP2E1 variant c2 allele polymorphisms on esophageal cancer risk with conjunction with alcoholic consumption, the present 1:3 matched case-control study was conducted. The 165 histologically diagnosed Japanese esophageal cancer cases were here compared with 495 randomly selected controls, matched with respect to sex and age. Conditional logistic regression was used to calculated Odds Ratios (ORs) and 95% confidence intervals (95% CI). Significant gene-environment interactions between alcohol drinking and both ADH2 and ALDH2 were observed regarding esophageal cancer risk. The ADH2 Arg47His polymorphism showed moderately increased risk (OR for Arg/His and Arg/Arg relative to His/His: 2.01 (1.39-2.90)). In the ALDH2 case, comparing the Glu/Lys with the Glu/Glu genotype, ORs were markedly increased to 9.64 (3.23-28.8) and 95.4 (28.7-317) from 1.88 (0.42-8.37) and 4.62 (0.93-23.1) for moderate drinking and heavy drinking, respectively. No significant alteration in risk was observed with the CYP2E1 polymorphism. In conclusion, the present study revealed a significant gene-environment interaction between alcohol drinking and the ALDH2 polymorphism regarding esophageal cancer risk among a general population in Japan, providing concrete evidence of a role for acetaldehyde in neoplastic development. Interactions between ALDH2 and ADH2 need further clarification.

A unique seroepidemiological pattern of HBV, HCV and HTLV-I in Nenets and Komi in northwestern Russia.

An epidemiological study of hepatitis viruses type B (HBV) and type C (HCV) and human T-cell leukemia virus type I (HTLV-I) was carried out among 105 residents (male:female=19:86) regarded as Nenets partly mixed with Komi, in the region of Krasnoe, the Nenets Autonomous District of the Arkhangelsk Region, in northwestern Russia in 2004. Blood was drawn from apparently healthy volunteers at ages of 41.6+/-16.5 (range 14-85) years. HBsAg, HBsAb, HBcAb, HBeAb and HCV Ab were measured by microparticle enzyme-immunoassay, and HTLV-I Ab was measured by particle agglutination. Prevalences of HBsAg(+), HBsAb(+), HBcAb(+) and HBeAb(+) were 0.0%, 29.5.%, 20.0% and 7.6%, respectively. The overall HBV infection rate (positive HBsAb or HBcAb) was 34.3%, while no positive HCV or HTLV-I Abs could be detected. A serological subgroup with positive HBsAb and negative HBcAb, consisting of 15(14.3%) females, contrasted sharply to other serological subgroups in sex, age, parent's ethnicity, positive HBeAb rate, and HBcAb inhibition%. We conclude that HBV is prevalent with unique serological patterns among the Nenets, while HCV and HTLV-I infections are negligible.

Risk factors for esophageal cancer: a case-control study in South-western China.

Esophageal cancer is a crucial cancer in China. Yanting in Sichuan Province was a key area with highest esophageal cancer mortality in China, but little evidence on esophageal cancer risk factors has been reported for this area and the etiology remains unclear. To clarify risk factors, a 1:1 matched case-control study was conducted. Totals of 185 eligible esophageal cancer patients and 185 healthy residents matched for sex and age were recruited. Conditional logistic regression was used to calculate odds ratios (ORs) and 95% confidence intervals (CIs) for possible risk/protective factors. All ORs were adjusted by family history of esophageal cancer and occupation, and then further adjusted by other possible confounding factors. Our results showed that smoking and alcohol drinking were risk factors for esophageal cancer with dose-response. The ORs (95% CI) compared with never smokers and drinkers were 4.06 (1.55-10.6) and 2.49 (1.06-5.85), respectively. The OR was further increased to 8.86 (95% CI, 3.82-20.5) for both smoking and drinking in combination. Eating food rapidly (OR=5.84, 95% CI, 2.05-16.7), drinking shallow ground water (OR=4.18, 95% CI, 1.30-13.4) and frequent intake of picked vegetables (OR=2.12, 95% CI, 1.00-4.49) appeared to increase the risk, while frequent intake of fresh fruit (OR=0.42, 95% CI, 0.19-0.89), fresh vegetables (OR= 0.62, 95% CI, 0.32-1.17) and eggs (OR=0.59, 95% CI, 0.25-1.39) decreased the risk. In conclusion, smoking and alcohol drinking are common in Yanting and main contributors to esophageal cancer. Consumption of fresh fruit and eggs are not common and high consumption of these two foods as well as fresh vegetables may decrease the risk of esophageal cancer in this area. In addition, drinking shallow ground water and eating food rapidly, as well as frequent intake of pickled vegetables, are also factors increasing the risk.

Relation of the CD36 gene A52C polymorphism to the risk of colorectal cancer among Japanese, with reference to with the aldehyde dehydrogenase 2 gene Glu487Lys polymorphism and drinking habit.

High consumption of white meat (or saturated fatty acids) and alcohol has been demonstrated to have a tendency to increase the risk of colorectal cancer, according to the level of malondialdehyde-deoxyguanosine adducts derived from lipid per-oxidation in the colorectal mucosa. CD36 plays important roles as a long-chain fatty acid translocase and oxidized low-density lipoprotein (LDL) scavenger, while alcohol is metabolized by aldehyde dehydrogenase 2 (ALDH2) and decreases transiently metabolism of dietary fat and serum lipids. To examine associations between the risk of colorectal cancer and the CD36 gene A52C polymorphism according to the ALDH2 gene Glu487Lys polymorphism and drinking habit, a hospital-based case-control study was conducted with 128 colorectal cancer cases and 238 cancer-free controls. Odds ratios (ORs) for the C/C genotype relative to the A/A genotype were 1.70 [95% confidence interval (CI), 0.76-4.11] and 4.24 (95% CI, 1.42-22.66) for men and women, respectively, with the low-activity (Glu/Lys + Lys/Lys) ALDH2 genotype. The high-activity (Glu/Glu) genotype for men and women had no associations. On the other hand, the OR for the C/C genotype with high frequency of drinking habit relative to the A/A genotype with low frequency of drinking habit among men was 3.63 (95% CI, 1.29-13.15). The number of women with a high frequency drinking habit was too small for any corresponding analyses. Our findings suggest a significant interaction between alcohol consumption and the CD36 gene A52C polymorphism related to the metabolism of long-chain fatty acids and oxidized LDL in the etiology of colorectal cancer.

An epidemiological study of HBV, HCV and HTLV-I in Sherpas of Nepal.

An epidemiological study of hepatitis viruses type B (HBV) and type C (HCV) and human T-cell leukemia virus type I (HTLV-I) was carried out among 103 residents (male:female=61:42) regarded as Sherpas, at Lukla (Solukhumbu district), Nepal in 2004. Blood was drawn from apparently healthy volunteers at ages of 28.8+12.3 (range 15-66) years. HBsAg, HBsAb, HBcAb, and HCV Ab were measured by microparticle enzyme-immunoassay, and HTLV-I Ab was measured by particle agglutination. Prevalence of HBsAg(+), HBsAb(+), HBcAb(+), and HBsAb(+) or HBcAb(+) were 1.9% 22.3%, 24.3%, and 28.2%, respectively. For HCV Ab, only a borderline reaction was observed in one sample, and for HTLV-I Ab all samples were negative. Nucleotide sequencing of the PreS1, PreS2, and S genes revealed that HBV among Sherpas to be of the A' (or Aa) genotype, which is prevalent among Nepalese but rare in native Tibetans, suggesting transmission within Nepal rather than association with ancestors' migration from Tibet as the origin. This is the first report of Himalayan Sherpas' state of infection with HBV, HCV, and HTLV-I.

Cervical cancer in the asian pacific-epidemiology, screening and treatment.

Squamous cell carcinoma (SCC) of the cervix continues to be a major problem in many areas of the Asian-Pacific, particularly in the Indian subcontinent and Papua New Guinea, and to a lesser extent in South-East Asia, Korea and Mongolia. In contrast, levels in the developed countries of the region are low, as is also the case for the Muslim countries of Western Asia, and mainland China. Incidence generally mirrora associated mortality, although with some exceptions reflecting facilities and infrastructure for early detection. Over the last 25 years there has been a marked decrease in incidence rates across most of the Asian Pacific, although less pronounced in India than elsewhere, and there are exceptions where the incidence is on the increase. The predominant risk factor is well established to be persistent infection with a high risk 'oncogenic' type of human papilloma virus (HPV), along with multiple partners, other sexually transmitted diseases and smoking. Consumption of vegetables, in contrast, appears to be protective. Hormonal factors may also play some role. Modifying factors may either impact on neoplasia by directly influencing the processes underlying carcinogenesis, or indirectly by affecting persistence of viral infections. For primary prevention, avoidance of repeated infections and smoking, as well as a high antioxidant intake may be beneficial. Vaccines against HPV also have promise for the future, but a better understanding of the mechanisms underlying spontaneous clearance of both infection and cervical intraepithelial neoplasia (CIN) of different grades is also essential for optimal intervention. For screening, the choice of whether the PAP smear, HPV testing or some form of visual inspection are utilized depends on the resources which are available, all approaches having their own advantages and disadvantages, but with similar sensitivity and specificity. One complication is the increase in adenocarcinoma of the cervix which has been reported in some countries, for which risk factors and most effective screening may differ from the SCC case. A focus on high risk groups like sex workers might be warranted where financial and technical support are limited. If cervical intraepithelial neoplasias are detected then cryotherapy or the loop electrosurgical excision procedure (LEEP) are effective for their removal. Control of cancer of the cervix, however, demands that a comprehensive approach to screening and management is adopted, necessitating major training of personnel and provision of appropriate resources.

Comparison of lifestyle risk factors by family history for gastric, breast, lung and colorectal cancer.

To assess the theoretical impact of lifestyle of a cancer family history in first-degree relatives (CFH) and clarify interactions between CFH and lifestyle factors, hospital-based comparison and case-reference studies were conducted in Nagoya, Japan. Totals of 1988 gastric, 2455 breast, 1398 lung and 1352 colorectal cancer patients, as well as 50,706 non-cancer outpatients collected from 1988 to 1998, were checked for lifestyle factors, which included dietary and physical exercise habits, as well as smoking/drinking status. General lifestyle factors with non-cancer outpatients did not differ by the CFH status. Case-reference analyses showed that frequent intake of fruits, raw vegetables, carrots, pumpkin, cabbage and lettuce, as well as frequent physical exercise, were associated with decreased risk for all four sites of cancer, while habitual smoking increasing the risk of gastric, and more particularly, lung cancer. Interestingly, the study revealed the magnitude of odds ratios for the above lifestyle factors obtained from CFH positives to be similar to those from CFH negatives for these four sites of cancer. There were no significant interactions between CFH and any particular lifestyle factor. In conclusion, our results suggest no appreciable influence of CFH on lifestyle related risk factors for gastric, breast, lung, and colorectal cancer. Habitual smoking increased, while frequent physical exercise and raw vegetables intake decreased cancer risk, regardless of the CFH status.

Estimation of cancer incidences in Aichi prefecture: use of a model area with good quality registry data.

In Japan, local government is responsible for organization of population-based cancer registries and the quality of the registration remains modest, mainly due to dependence on voluntary-based operations without legal obligations. Aichi Prefecture cancer registry covers a large population, estimated at 7 million, and its quality has yet to reach the level required internationally. The derived cancer incidences for Aichi Prefecture therefore tend to be underestimated. In the present study we set up a model area, located in the central part of Aichi Prefecture, with a good quality of registry data, covering a reasonable population, including both urban and rural areas. Our model area has typical demographic features of Aichi Prefecture. The materials were data on cancer incidence and deaths during the period of 1996-2000 in this model area of Aichi prefecture, with a population of approximately one million, under the jurisdiction of three public health centers, covering nine municipalities. The percentage of death certificated notified (DCN) cases for all sites was around 14% and the incidence/death ratio was around 1.9. Estimated age-adjusted incidence rates were found to be 256.0 (per 100,000) for males and 177.6 for females, these values being 10-15 % higher than those generated using data for the whole prefecture, and quite close to incidence rates in Japan estimated from the highest quality of data available. It is suggested that the cancer incidence in the Aichi prefecture is indeed being underestimated and that the actual figures may be closer to the estimates provided here.