Meta- and pooled analyses of the methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism and colorectal cancer: a HuGE-GSEC review.

Worldwide, over 1 million cases of colorectal cancer (CRC) were reported in 2002, with a 50% mortality rate, making CRC the second most common cancer in adults. Certain racial/ethnic populations continue to experience a disproportionate burden of CRC. A common polymorphism in the 5,10-methylenetetrahydrofolate reductase (MTHFR) gene has been associated with a lower risk of CRC. The authors performed both a meta-analysis (29 studies; 11,936 cases, 18,714 controls) and a pooled analysis (14 studies; 5,068 cases, 7,876 controls) of the C677T MTHFR polymorphism and CRC, with stratification by racial/ethnic population and behavioral risk factors. There were few studies on different racial/ethnic populations. The overall meta-analysis odds ratio for CRC for persons with the TT genotype was 0.83 (95% confidence interval (CI): 0.77, 0.90). An inverse association was observed in whites (odds ratio = 0.83, 95% CI: 0.74, 0.94) and Asians (odds ratio = 0.80, 95% CI: 0.67, 0.96) but not in Latinos or blacks. Similar results were observed for Asians, Latinos, and blacks in the pooled analysis. The inverse association between the MTHFR 677TT polymorphism and CRC was not significantly modified by smoking status or body mass index; however, it was present in regular alcohol users only. The MTHFR 677TT polymorphism seems to be associated with a reduced risk of CRC, but this may not hold true for all populations.

The 15-Country Collaborative Study of Cancer Risk Among Radiation Workers in the Nuclear Industry: design, epidemiological methods and descriptive results.

Radiation protection standards are based mainly on risk estimates from studies of atomic bomb survivors in Japan. The validity of extrapolations from the relatively high-dose acute exposures in this population to the low-dose, protracted or fractionated environmental and occupational exposures of primary public health concern has long been the subject of controversy. A collaborative retrospective cohort study was conducted to provide direct estimates of cancer risk after low-dose protracted exposures. The study included nearly 600,000 workers employed in 154 facilities in 15 countries. This paper describes the design, methods and results of descriptive analyses of the study. The main analyses included 407,391 nuclear industry workers employed for at least 1 year in a participating facility who were monitored individually for external radiation exposure and whose doses resulted predominantly from exposure to higher-energy photon radiation. The total duration of follow-up was 5,192,710 person-years. There were 24,158 deaths from all causes, including 6,734 deaths from cancer. The total collective dose was 7,892 Sv. The overall average cumulative recorded dose was 19.4 mSv. A strong healthy worker effect was observed in most countries. This study provides the largest body of direct evidence to date on the effects of low-dose protracted exposures to external photon radiation.

The 15-Country Collaborative Study of Cancer Risk among Radiation Workers in the Nuclear Industry: estimates of radiation-related cancer risks.

A 15-Country collaborative cohort study was conducted to provide direct estimates of cancer risk following protracted low doses of ionizing radiation. Analyses included 407,391 nuclear industry workers monitored individually for external radiation and 5.2 million person-years of follow-up. A significant association was seen between radiation dose and all-cause mortality [excess relative risk (ERR) 0.42 per Sv, 90% CI 0.07, 0.79; 18,993 deaths]. This was mainly attributable to a dose-related increase in all cancer mortality (ERR/Sv 0.97, 90% CI 0.28, 1.77; 5233 deaths). Among 31 specific types of malignancies studied, a significant association was found for lung cancer (ERR/Sv 1.86, 90% CI 0.49, 3.63; 1457 deaths) and a borderline significant (P = 0.06) association for multiple myeloma (ERR/Sv 6.15, 90% CI <0, 20.6; 83 deaths) and ill-defined and secondary cancers (ERR/Sv 1.96, 90% CI -0.26, 5.90; 328 deaths). Stratification on duration of employment had a large effect on the ERR/Sv, reflecting a strong healthy worker survivor effect in these cohorts. This is the largest analytical epidemiological study of the effects of low-dose protracted exposures to ionizing radiation to date. Further studies will be important to better assess the role of tobacco and other occupational exposures in our risk estimates.

Dietary factors and stomach cancer: a case-control study in Korea.

BACKGROUND: Stomach cancer is the most common cancer among Koreans. There is wide agreement that dietary factors are important in gastric carcinogenesis, but the role of many Korean food items remains unknown. METHODS: A case-control investigation involving 213 incident cases of histologically confirmed stomach cancer and an equal number of controls, matched by age (within 2 years) and sex, was conducted from June 1990 to October 1991. RESULTS: An increased risk of stomach cancer was noted among those with high consumption of stewed foods such as soybean paste stew and hot pepper-soybean stew, broiled fish, and those who liked salty food. However, mung bean pancake, tofu (soybean curd), cabbage, spinach, and sesame oil decreased the risk of stomach cancer. Stratified analysis by salt in combined foods, such as stewed foods and pickled vegetables, disclosed salt as being an important risk factor. Analysis of cooking methods showed that broiling and salting increased the risk of stomach cancer, but that frying tended to decrease the risk. These results suggest that the cooking method might modify the gastric carcinogenicity of foods. As non-dietary factors, smoking and a family history of stomach cancer increased the risk, but use of a refrigerator decreased the risk of cancer. CONCLUSIONS: Heavy salt consumption and cooking methods like broiling and salting seem to play a major role in gastric carcinogenesis among Koreans.

Lack of familial clustering of hepatitis C virus infection.

BACKGROUND: Although transmission of hepatitis C virus (HCV) through parental exposure is well documented, it is still controversial whether familial clustering of HCV occurs. METHODS: To investigate risk factors for HCV infection, 109 cases and 84 non-infected controls were studied. In addition, 250 family members (104 men, 146 women) of cases and 170 family members of controls (64 men, 106 women) were tested for HCV infection using an anti-HCV antibody, alanine aminotransferase (ALT), and reverse transcribed polymerase chain reaction (RT-PCR). RESULTS: In the case-control analysis, people aged > or =60 were almost three times more likely to be infected by HCV than those aged <40. Risk of HCV infection was most strongly related to a history of blood transfusion (OR = 12.6, 95% CI: 4.3-36.5) followed by a history of jaundice (OR = 4.1, 95% CI: 1.3-12.6). Only one family member of cases and no-one related to the controls had HCV infection. CONCLUSIONS: These results suggest that, in Korea, age and parenteral exposure, such as a blood transfusion, are risk factors for HCV infection and familial clustering of HCV infection, if it occurs, is rare.

Hepatitis B and C virus, Clonorchis sinensis for the risk of liver cancer: a case-control study in Pusan, Korea.

BACKGROUND: Liver cancer mortality in Korea is the highest in the world. Hepatitis B and C viruses (HBV, HCV) are known to be the major risk factors of hepatocellular carcinoma (HCC). Cholangiocarcinoma (CLG) accounts for more than 20% of liver cancer in the Pusan area. In Korea, the different roles of known risk factors in the development of HCC or CLG have not been adequately evaluated. METHODS: Case-control studies involved 203 incident HCC cases, 406 controls matched to the HCC cases for age (+/- 4 years) and sex, and 41 CLG cases (the HCC controls were used). They were carried out from August 1990 to August 1993. RESULTS: Relative risk (RR) of HBsAg (87.4; 95% confidence interval [CI]: 22.2-344.3) and RR of anti-HCV positivity (30.3; 95% CI: 6.1-150.6) were significant for the risk of HCC after adjustment for potentially confounding factors. In contrast, RR of Clonorchis sinensis in stool (2.7; 95% CI: 1.1-6.3) and RR of heavy drinking (4.6; 95% CI: 1.4-15.2) were significant for the risk of CLG. Transfusion history, acupuncture history, and cigarette smoking were not associated with the risk of HCC or CLG. CONCLUSIONS: Strong evidence indicated that both HBV and HCV infection were independent risk factors for HCC. In contrast, C. sinensis in stools and heavy drinking were associated with the risk of CLG in Korea.

Hepatitis B vaccination and reduced risk of primary liver cancer among male adults: a cohort study in Korea.

BACKGROUND: Primary liver cancer is an important health problem in Korea, where hepatitis B virus (HBV) infection is prevalent. The authors conducted a prospective cohort study to evaluate the protective effect of HBV vaccination against liver cancer in adults. METHODS: A total of 370,285 males aged > or = 30 comprised the study population. They were clinically free of liver diseases, and had not been vaccinated against HBV at enrolment. The results of HBV surface antigen (HBsAg) and antibody to HBsAg (anti-HBs) marker positivity and those of the vaccination programme which took place during 1985 were used for the construction of the cohort. About 5% (n = 18,914) were HBsAg positive, 78,094 were anti-HBs positive, and 273,277 were negative for both. Among the candidates for HBV vaccination (n = 273,277), 35,934 (13.2%) people had been vaccinated against HBV during 1985. Cases of liver cancer were ascertained by record linkage and from medical records covering 1986-1989. A multivariate log-linear model was used to test statistical significance and to estimate relative risks (RR). RESULTS: The total follow-up period was 1,404,566 person-years, with an average of 3 years and 10 months. A total of 302 incident cases were ascertained. The overall incidence rate of liver cancer was 21.7 per 100,000 person-years. With reference to the incidence level among the unvaccinated and uninfected, the RR of primary liver cancer among the chronically infected and that of the unvaccinated and infected was 18.1 (95% CI: 14.2-22.9) and 0.34 (95% CI: 0.19-0.60), respectively. The RR among the vaccinated group was 0.58 (95% CI: 0.31-1.09). CONCLUSIONS: This study suggested that artificial immunization through HBV vaccination, even in adulthood, reduces the risk of liver cancer. It might also offer a practicable means of primary prevention, especially in areas with hyperendemicity of HBV infection.

Vegetables, cereals and colon cancer mortality: long-term trend in Japan.

Vegetables, cereals and meat are foods of interest in the aetiology of colon cancer. While vegetable consumption is considered to be protective against colon cancer, the role of cereals in colon carcinogenesis remains controversial. Colon cancer mortality has rapidly increased in Japan since the 1950s. We examined the trend of consumption of vegetables, cereals and meat in Japan during the period from 1950 to 1995. Vegetable consumption has been almost constant during the period, whereas cereal consumption has declined drastically. Meat consumption increased up until the 1970s, but the increase has been minimal thereafter. These consumption patterns suggest that cereals are an important dietary factor determining the risk of colon cancer in Japan.

Cancer survival in Seoul, Republic of Korea, 1993-1997.

The Seoul cancer registry was established in 1991. Cancer is a notifiable disease, and registration of cases is done by passive and active methods. The registry contributed survival data for 56 cancer sites or types registered during 1993-1997. Follow-up information has been gleaned predominantly by passive methods with median follow-up ranging between 5-82 months for various cancers. The proportion with histologically verified diagnosis for different cancers ranged between 23-99%; death certificates only (DCOs) comprised 0-67%; 33-100% of total registered cases were included for survival analysis. The top-ranking cancers on 5-year age-standardized relative survival rates were testis and placenta (95%), thyroid (93%), non-melanoma skin (93%), corpus uteri (79%), renal pelvis (77%), cervix (76%), Hodgkin lymphoma (75%), breast (74%) and prostate (74%). Five-year relative survival by age group showed a decreasing trend with increasing age groups for cancers of the small intestine, colon, gall bladder, cervix, corpus uteri, ovary, kidney, urinary bladder and thyroid, or was fluctuating for other cancers.

Folate intake and the risk of colorectal cancer in a Korean population.

BACKGROUND: Folate, a water-soluble B vitamin and one of the major micronutrients in vegetables, is known as an essential factor for the de novo biosynthesis of purines and thymidylate, and it plays an important role in DNA synthesis and replication. Thus, folate deficiency results in ineffective DNA synthesis, and has been shown to induce the initiation and progression of colorectal cancer (CRC). Recently, the incidence of CRC in Korea has increased markedly in both men and women; this trend may be related to the adoption of a more 'westernized' lifestyle, including dietary habits. OBJECTIVE: A hospital-based case-control study was conducted to examine the relationship between folate intake and the risk of CRC within a Korean population. METHODS: A total of 596 cases and 509 controls, aged 30-79 years, were recruited from two university hospitals. Site- and sex-specific odds ratios (ORs) were estimated using logistic regression models. RESULTS: Cases were more frequently found to have a family history of CRC among first-degree relatives, to consume more alcohol, to be more likely current smokers and less likely to participate in vigorous physical activity than the controls. In the overall data for men and women combined, multivariate ORs (95% confidence interval (CI), P for trend) comparing the highest vs the lowest quartile of dietary folate intake were: 0.47 (0.32-0.69, <0.001) for CRC, 0.42 (0.26-0.69, <0.001) for colon cancer and 0.48 (0.28-0.81, 0.007) for rectal cancer. An inverse association was also found in women with dietary folate intake: 0.36 (0.20-0.64, <0.001) for CRC, 0.34 (0.16-0.70, 0.001) for colon cancer and 0.30 (0.12-0.74, 0.026) for rectal cancer, but not in men. In addition, the total folate intake of women was strongly associated with a reduced risk of rectal cancer (OR, 0.38; 95% CI, 0.17-0.88; P for trend=0.04). CONCLUSION: We found a statistically significant relationship between higher dietary folate intake and reduced risk of CRC, colon cancer and rectal cancer in women. A significant association is indicated between higher total folate intake and reduced risk of rectal cancer in women.

Risk of cancer after low doses of ionising radiation: retrospective cohort study in 15 countries.

OBJECTIVES: To provide direct estimates of risk of cancer after protracted low doses of ionising radiation and to strengthen the scientific basis of radiation protection standards for environmental, occupational, and medical diagnostic exposures. DESIGN: Multinational retrospective cohort study of cancer mortality. SETTING: Cohorts of workers in the nuclear industry in 15 countries. PARTICIPANTS: 407 391 workers individually monitored for external radiation with a total follow-up of 5.2 million person years. MAIN OUTCOME MEASUREMENTS: Estimates of excess relative risks per sievert (Sv) of radiation dose for mortality from cancers other than leukaemia and from leukaemia excluding chronic lymphocytic leukaemia, the main causes of death considered by radiation protection authorities. RESULTS: The excess relative risk for cancers other than leukaemia was 0.97 per Sv, 95% confidence interval 0.14 to 1.97. Analyses of causes of death related or unrelated to smoking indicate that, although confounding by smoking may be present, it is unlikely to explain all of this increased risk. The excess relative risk for leukaemia excluding chronic lymphocytic leukaemia was 1.93 per Sv (< 0 to 8.47). On the basis of these estimates, 1-2% of deaths from cancer among workers in this cohort may be attributable to radiation. CONCLUSIONS: These estimates, from the largest study of nuclear workers ever conducted, are higher than, but statistically compatible with, the risk estimates used for current radiation protection standards. The results suggest that there is a small excess risk of cancer, even at the low doses and dose rates typically received by nuclear workers in this study.

Diet and stomach cancer in Korea.

Stomach cancer is the most prevalent malignant neoplasm in Korea. As of 1991-1992 in Seoul, the cumulative rates reported for the age span 0-74 were 7.6% in males and 3.1% in females. A recent case-control study reported that several food items and cooking methods are associated with increased or decreased risk of stomach cancer among Koreans. An increased risk of stomach cancer was noted among people who frequently consume broiled meats and fishes, salted side dishes (salted/fermented fish products) and salty stewed foods, such as soybean paste thick stew. Frequent consumption of mung bean pancake, tofu, cabbage, spinach and sesame oil decreased the risk. Analysis by cooking method showed that risk of stomach cancer from the same foods varied with preparation. For meat and fish, pan frying was associated with decreased risk, whereas stewing or broiling was associated with increased risk. Pickled vegetables increased the risk, whereas fresh vegetables did not. In a recent cohort study in Seoul, green vegetables and soybean foods were associated with a decreased risk of stomach cancer. Case-control and cohort studies have reported that ginseng intake decreased the risk of gastric cancer.

Strategy for vaccination against hepatitis B in areas with high endemicity: focus on Korea.

Hepatitis B vaccination strategies may vary from country to country depending on hepatitis B virus (HBV) endemicity, predominant modes of infection, age of infection, and health care resources. In areas with high endemicity like Korea, transmission of virus from carrier mothers to infants during the perinatal period, and from other horizontal sources to infants and children, account for most cases of HBV infection. The consequences of HBV infection at an early age are serious, as more than 70% remain chronic carriers of the virus. These chronic carriers are the principal source of infection for other susceptible people, and are themselves at high risk of developing other serious diseases, such as chronic hepatitis, liver cirrhosis, and hepatocellular carcinoma. Theoretically, therefore, routine infant immunisation supplemented with prenatal screening of pregnant women for HBsAg or HBeAg and mass immunisation of children is the appropriate strategy for control of hepatitis B in these countries. To prevent primary liver cancer associated with HBV infection, however, immunisation of adults at high risk would also be prudent. Mandatory vaccination of all neonates is recommended in highly endemic areas, together with hepatitis B immune globulin in babies born to HBsAg carrier mothers.

Factors associated with intrafamilial transmission of hepatitis B virus infection in Korea.

Epidemiologic and serologic data on 137 household contacts of 51 chronic carriers of HBsAg and 111 household contacts of 38 controls who were negative for serologic markers of hepatitis B virus (HBV) were obtained from March 1990 to August 1991. Using this data, possible routes of intrafamilial transmission of hepatitis B virus among household contacts of chronic carriers of hepatitis B surface antigen (HBsAg) were evaluated and analyzed. The HBsAg prevalence among the household contacts of carriers was 14. 1% (95% CI 7.8-24.0) compared to 0.0% (95% CI 0.0-7.0) among those of controls (P < 0.01). The offspring of carriers showed significantly higher risk of HBV infection(relative risk; 6.6). Sharing of towels and handkerchieves, and drinking vessels was associated with an increased risk of HBV infection via intrafamilial transmission in Korea (relative risk 11.5 for towel and handkerchief, 12.1 for drinking vessels).

Incidence pattern of colorectal cancer in Korea by subsite of origin.

It has been suggested that colorectal cancer might not be one homogenous disease entity, based on the distinctive characteristics of its subsite of origin. Incidence data on 4,987 colorectal cancer were obtained from the Seoul Cancer Registry between 1993 and 1995. Age, sex, and subsite-specific incidence rates were compared. The age-standardized annual incidence rates of total colorectal cancer were 26.1 and 18.0 per 100,000 for men and women, respectively. There were no appreciable difference in the rates of colon and rectal cancer for either sex (colon vs rectum: 12.8 vs. 13.2 for men, 9.3 vs. 8.6 for women). The incidence rate of right colon was slightly higher in men than in women, and this discrepancy became even greater in left colon (men vs women: 3.5 vs. 3.0 for right colon, 4.7 vs. 2.9 for left colon). When the incidence rate of right colon was compared with that of left colon, women had a higher rate in the right colon among the elderly, aged 60 yr and over and a lower rate at age 40 yr or less, while the opposite was observed for men. More analytic approaches are needed to identify which factors are related with these descriptive results in colorectal cancer incidence.

Familial clustering of hepatitis B and C viruses in Korea.

In order to evaluate the familial clustering of hepatitis B virus(HBV) and hepatitis C virus(HCV) infections and to elucidate the possible routes of HCV transmission among Korean adults with chronic liver disease, 137 household contacts of 51 chronic carriers of HBsAg and 111 household contacts of 38 controls, and 181 household contacts of 96 anti-HCV positives and 102 household contacts of 76 anti-HCV negatives were tested from July 1990 to March 1994. Of 71 non-vaccinated household contacts of HBsAg carriers, 10 gave positive result for HBsAg(14.1%), but none of the household contacts of the controls were positive for HBsAg(p < 0.05). Familial clustering of HBV infection was found, when the offspring of carriers and controls were compared. A significantly higher percentage of the offspring of carriers were positive for HBV infection(54.6% vs 15.4%, p < 0.05) with OR of 6.6(95% Cl; 1.3-34.5). No evidence of familial clustering of HCV infection was found with 2.2%(4/181) anti-HCV positivity among the household contacts of index cases, similar to 1.0%(1/102) among those of controls. History of acute hepatitis(OR 3.2), transfusion(OR 3.2), and acupuncture(OR 2.5) were associated with an increased risk of HCV infection. In conclusion, HBV has strong familial clustering whereas HCV does not in Korea.

Epidemiologic and clinical characteristics of migraine and tension-type headache in Korea.

This is the first population-based epidemiologic study of chronic headache in South Korea. The diagnosis and classification of headache was according to the criteria of the International Headache Society. Sixty-eight percent of the studied population experienced headache during the preceding year. The estimated prevalences were 22.3% for migraine (male 20.2%, female 24.3%) and 16.2% for tension-type headache (male 17.8%, female 14.7%). In migraine, the 15- to 19-year age group showed maximal prevalence in both sexes (male 28.5%, female 34.7%). The prevalence of tension-type headache was highest in the 50- to 59-year age group in men (24.2%) and in the 20- to 29-year age group in women (20.2%). In migraine, headache intensity was more severe in women than in men, but in tension-type headache there was no difference in the severity of headache between the sexes. Phonophobia was the most common associated symptom of migraine (65.1%). In the migraine with aura group, the most common aura was visual disturbance, including scintillation and image distortion (82.3%). Only 24.4% of migraineurs and 12.3% of patients with tension-type headache had ever consulted a doctor for headache. The prevalence of migraine was not lower than in western countries and much higher than in previous studies conducted in other Asian countries.

A case-control study on the risk factors of hepatitis C virus infection among Koreans.

In order to identify the risk factors for hepatitis C virus (HCV) infections, a case-control study was conducted from September 1993 to April 1994. HCV infection was confirmed by the second generation of recombinant immunoblot assay. Sixty-four cases and 128 controls matched for age and sex with a 1:2 ratio of cases to controls were enrolled. Exposure data were obtained from all participants by self-administered questionnaire and the odds ratios of possible risk factors of HCV infection analysed. Sixty-four cases consisted of forty-two patients with chronic hepatitis, nine with cirrhosis, one with hepatocellular carcinoma, and twelve with normal liver function. History of acute hepatitis (OR 3.9) and transfusion (OR 2.4) were associated with an increased risk of HCV infection. Operation, acupuncture, endoscopy, tooth extraction, tattooing, ear piercing, needle sharing and family history of hepatitis were not associated with an increased risk of HCV infection. In conclusion, transfusion remains the major route of transmission of HCV in Korea.

Factors associated with positive predictability of the anti-HCV ELISA method with confirmatory RT-PCR.

The positive predictability of anti-HCV ELISA is low, especially, in blood donors and in healthy populations. False positive anti-HCV results pose some difficulties in medical practice and in blood screening. The aim of this study was to identify the factors associated with true hepatitis C virus (HCV) infection among anti-HCV ELISA-positives. A case-control analysis was conducted using 354 subjects who were positive for anti-HCV ELISA. All subjects were tested for true HCV infection using the reverse transcriptase polymerase chain reaction (RT-PCR). Tests for serum alanine aminotransferase (ALT), fasting glucose, HBsAg, anti-HBc antibody, alpha-fetoprotein, platelet count and ultrasound of liver were also performed. Epidemiological data were obtained by self-administered questionnaires. Out of 354 subjects, 202 (57.1%) were positive for HCV by RT-PCR and 152 were negative and used as the control group. In multivariate analysis, blood transfusion (odds ratio, OR 2.3, 95% confidence interval, CI 1.3-4.0), elevated ALT (OR 2.2, 95% CI 1.2-4.3) and higher anti-HCV ELISA ratios (more than 3; OR 1.7, 95% CI 1.3-2.1) were associated with true HCV infection. Thrombocytopenia was also associated with the presence of HCV in univariate analysis. These results suggest that a history of blood transfusion, elevated ALT and a high score on anti-HCV ELISA ratios are associated with true HCV infection among anti-HCV ELISA-positives.

Cancer and other causes of death among Koreans in Fukuoka, Japan, 1976-1986.

Mortalities from cancer and other causes among Koreans living in Fukuoka, Japan, between 1976 and 1986 were examined as compared with those of Japanese in the prefecture. Korean males had a marked excess in all-cause mortality, while the excess among females was less prominent. In both sexes, mortalities from liver cancer, liver cirrhosis, accident and suicide were markedly increased in the Korean population. These findings are in agreement with those observed among Koreans in Osaka. Although 20-30% lower-than-Japanese mortality from stomach cancer has been reported for Koreans in Osaka, those in Fukuoka had a risk of this cancer comparable to that of Japanese. A life-style survey of Koreans in Japan might provide a better understanding of the disease patterns observed in this population.