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Epidemiologic evidence suggests that chronic inflammatory conditions of the lung may increase lung cancer risk. These chronic conditions, such as chronic obstructive pulmonary disease and asthma, commonly coexist with chronic rhinosinusitis. We prospectively examined if chronic rhinitis or sinusitis was associated with lung cancer risk in the Singapore Chinese Health Study, a population-based cohort of 63,257 Singapore Chinese, who were aged 45-74 years when recruited between 1993 and 1998. Each subject completed a comprehensive interview on medical conditions, dietary and lifestyle factors at recruitment, and cancer occurrence and survival status were determined via linkage to population-based registries. As of 31 December, 2005, 954 cohort participants had developed lung cancer. Compared with subjects without such history, subjects who reported a history of physician-diagnosed rhinitis or sinusitis at baseline, whether allergic or nonallergic, had a statistically significant 59% increase in risk of lung cancer (hazard ratio [HR] = 1.59; confidence interval [CI] = 1.06-2.37). This association was significant and stronger in women (HR = 2.32; 95% CI = 1.23-4.39) compared to men, and for the adenocarcinoma cell type (HR = 1.91; 95% CI = 1.07-3.42) compared to other histologies. Overall, a history of asthma, hay fever, allergic dermatitis, food allergy or any other allergic conditions asked in a single question was not related to lung cancer risk (HR = 1.11; 95% CI = 0.90-1.36). Chronic rhinosinusitis may be a marker of pan-airway inflammation and its association with lung cancer risk provides evidence linking inflammation to lung carcinogenesis, especially among women., (Copyright 2008 Wiley-Liss, Inc.)

Endometrial cancer is the second most common cancer in hereditary nonpolyposis colorectal cancer (HNPCC). It has often been overlooked to explore the possibility of HNPCC in endometrial cancer patients. Our study was to investigate how many HNPCC patients existed among endometrial cancer patients. Among patients who underwent hysterectomy for endometrial cancer at Seoul National University Hospital from 1996 to 2004, 113 patients were included, whose family history and clinical data could be obtained and tumor specimens were available for microsatellite instability (MSI) testing and immunohistochemical (IHC) staining of MLH1, MSH2 and MSH6 proteins. There were 4 (3.5%) clinical HNPCC patients fulfilling the Amsterdam criteria II, and 2 (2/4, 50%) of them carried MSH2 germline mutations. There were also 8 (7.1%) suspected HNPCC (s-HNPCC) patients fulfilling the revised criteria for s-HNPCC, and one (1/8, 12.5%) of them revealed MLH1 germline mutation. In 101 patients, who were not clinical HNPCC or s-HNPCC, 11 patients showed both MSI-high and loss of expression of MLH1, MSH2 or MSH6 proteins, and 2 (2/11, 18.2%) of them showed MSH6 germline mutations. In 113 patients with endometrial cancer, we could find 5 (4.4%) HNPCC patients with MMR germline mutation and 2 (1.8%) clinical HNPCC patients without identified MMR gene mutation. Family history was critical in detecting 3 HNPCC patients with MMR germline mutation, and MSI testing with IHC staining for MLH1, MSH2 and MSH6 proteins was needed in the diagnosis of 2 HNPCC patients who were not clinical HNPCC or s-HNPCC, especially for MSH6 germline mutation., ((c) 2007 Wiley-Liss, Inc.)

Cervical cancer is a major health problem for Korean women, accounting for 9.8% of new female cancer cases, even though incidence rates have been decreasing. The Korean cervical cancer mortality rate for 1993-2002 based on National Statistical Office data shows an increasing trend, but the actual rates are thought to have decreased by epidemiologists, clinicians and other cancer experts. To explain this gap and solve this problem, we corrected the number of cervical cancer deaths by comparing death certificate cases of unspecified uterine cancer data with the national cancer incidence databases of entire cancer registries in Korea. We used 2 different methods to make a correction. First, we considered "uterus, unspecified" deaths previously registered as "cervix, uterine" cases misclassified and added them to the cervical cancer deaths. Alternatively, we multiplied the total number of registered unspecified uterine cancer deaths by age-specific proportions of registered incident cervical cancer cases among all cancers and added the product to cervical cancer deaths. The overall corrected age-standardized cervical cancer mortality rates per 100,000 women decreased from 5.2 in 1993 to 3.9 in 2002 (estimated annual percentage change (EAPC): -4.05%, 95% CI: -4.88, -3.22). While cervical cancer mortality showed a decreasing tendency in women aged 30-69 years, it increased substantially in women aged > or =70 years (EAPC: 3.62%, 95% CI: 1.92-5.35). Results of this study will provide evidence-based foundation for the evaluation of the existing cervical cancer-screening programs., (Copyright 2007 Wiley-Liss, Inc.)

The incidence of cervical adenocarcinoma (CA) is rising, whereas the incidence of cervical squamous cell carcinoma (CSCC) continues to decrease. However, it is still unclear whether different molecular characteristics underlie these 2 types of cervical carcinoma. To better understand the epigenetic characteristics of cervical carcinoma, we investigated the DNA promoter hypermethylation profiles in CA and CSCC. In addition, we investigated whether DNA hypermethylation patterns might be used for the molecular diagnosis of CA and endometrial adenocarcinoma (EA). Using the bisulfite-modification technique and methylation-specific PCR, we examined the aberrant promoter hypermethylation patterns of 9 tumor suppressor genes (APC, DAPK, CDH1, HLTF, hMLH1, p16, RASSF1A, THBS1 and TIMP3) in 62 CSCCs, 30 CAs and 21 EAs. After Bonferroni correction adjustment (statistically significant at p < 0.0055), we found that the aberrant hypermethylations of CDH1 and DAPK were more frequent in CSCCs than in CAs (80.6% vs. 43.3%, p = 0.001; 77.4% vs. 46.7%, p = 0.005), whereas HLTF and TIMP3 were more frequently methylated in CAs (3.2% vs. 43.3%, p < 0.001; 8.1% vs. 53.3%, p = 0.001). The hypermethylations of RASSF1A and APC were more frequent in CAs than in CSCCs, but this was not significant (9.7% vs. 33.3%, p = 0.008; and 14.5% vs. 40.0%, respectively, p = 0.009). In addition, RASSF1A hypermethylation was significantly more frequent in EAs than in CAs (81.0% vs. 33.3%, p = 0.001). In conclusion, the existence of these unique methylation patterns in these cancers suggests that their tumorigenesis may involve different epigenetic mechanisms., (2005 Wiley-Liss, Inc.)

Younger women who develop breast cancer are hypothesized to have poorer survival rates than women who develop it at a later stage in life. Several studies have suggested that differences in biologic characteristics of breast cancer in younger (premenopausal) and older (postmenopausal) women may account for the prognostic variation. This population-based cohort study reports on survival rates of breast cancer in Singapore and examines the hypothesis that younger breast cancer patients have a poorer prognosis. A total of 6,397 breast cancer patients diagnosed from 1968 to 1992 were identified from the population-based cancer registry and followed up through 1997. Outcome measures were relative survival rates (RSRs) calculated using Hakulinen's method and excess hazards ratios (HRs) derived from a regression model based on relative survival. The 2-, 5- and 10-year RSRs were worse among those aged > 75 (65%, 48% and 39%, respectively). The best survival rates were seen among those aged 40-44 (84%, 67% and 56%). Patients younger than 35 years faired reasonably well (79%, 60% and 50%). When the data were stratified according to clinical stage and calendar year, the highest risk of excess deaths was found in women > or = 75 years old. In patients with localized cancer and/or regional metastases, those in the 35-39 age group had the lowest excess risk. In patients with distant metastases, those younger than 35 years of age had the lowest excess risk of death. At the population level, younger women (< 45 years) with breast cancer in Singapore have higher relative survival rates., (Copyright 2003 Wiley-Liss, Inc.)

Reasons for the recent trend of increasing breast cancer incidence among Chinese and other Asian women are not well understood. Endogenous estrogen levels are strongly associated with breast cancer risk and its determinants include both genetic and lifestyle factors. We conducted a nested case-control study to investigate, within the Singapore Chinese Health Study Cohort, the relationships between polymorphisms in 2 genes involved in estrogen metabolism, CYP17 and HSD17B1, and the risk of breast cancer. For this analysis, 188 incident breast cancer cases and 671 female cohort control subjects were compared. When the HSD17B1 A allele was considered as the "putative high-risk" allele, there was a modest increased risk (adjusted relative risk, RR=1.37, 95% CI=0.90-2.07 for HSD17B1 AA vs. other); this association was statistically significant in analysis restricted to postmenopausal women (RR=1.86, 95% CI=1.14-3.03). There was no significant association between the CYP17 MspAI polymorphism and risk in all subjects (RR=1.06, 95% CI=0.65-1.74 for CYP17 A2A2 vs. CYP17 A1A1) or in postmenopausal women only. When we evaluated breast cancer risk in relation to the joint stratification of CYP17 and HSD17B1 genotypes and according to the combined number of putative high-risk alleles (range, 0-4), we observed an elevated joint effect of the CYP17 and HSD17B1 genes on risk. Women who possessed all 4 putative high-risk alleles of both genes (CYP17 A2A2 and HSD17B1 AA) vs. less displayed a nearly 2-fold increased risk (RR=1.83, 95% CI=0.97-3.44); this finding was statistically significant in postmenopausal women (RR=2.31, 95% CI=1.07-4.98). Risk of breast cancer was similar among women possessing the other genotypes (i.e., less than 4 putative high-risk alleles in the joint CYP17/HSD17B1 genotypes). In addition, the significant increased risk of breast cancer associated with nulliparity or late age at first live birth (age 31 years or older) was largely limited to women with the high-risk CYP17 A1A2/A2A2 or HSD17B1 AA genotypes (RR=2.41, 95% CI=1.56-3.72; RR=4.39, 95% CI=1.71-11.30, respectively). The latter gene-parity effects were especially pronounced in postmenopausal women., (Copyright 2003 Wiley-Liss, Inc.)

Since the 1980s, colorectal cancer incidence in Singapore has ranked second to lung in males and females. We describe a population-based analysis of survival of colorectal cancer patients diagnosed from 1968 to 1992 in Singapore. Data of colorectal cancer patients diagnosed during 1968-1992 were retrieved from the Singapore Cancer Registry. Patients were passively followed up for death to the end of 1997. The final dataset consisted of 10,114 subjects. Observed and relative survival rates were calculated by stage (localized, regional metastases and distant metastases), age, ethnicity and calendar period for both genders. Over the study period, a significant progress in survival of colorectal cancer patients was observed. For localized cancer of the colon, the 5-year age-standardized relative survival (ASRS) increased from 36% in 1968-1972 to 66% in 1988-1992 for males and from 32 to 71% for females. For localized rectal cancer, the 5-year ASRS improved from 25 to 66% for males and from 23 to 66% in females. Similarly, improvement was observed in colorectal cancer patients with regional metastases, but not in those with distant metastases. Calendar year period and clinical stage of disease were identified as major significant prognostic factors of survival for colorectal cancer. The substantially improved colorectal cancer survival rates reflected the interplay of cancer control activities in various areas, such as health promotion, early diagnosis and treatment. Our study shows a unique changing pattern of survival experience for colorectal patients from a country undergoing rapid economic development., (Copyright 2002 Wiley-Liss, Inc.)

The factors associated with risk of lung cancer among nonsmokers have not been fully elucidated, but dietary factors have consistently been shown to play a role. Chinese women are unique in having a high incidence of lung cancer despite a low smoking prevalence. This population is also known to have a high intake of soy, a dietary source of phytoestrogens. We conducted a hospital-based case-control study among Singapore Chinese women, comprising 303 cases and 765 age-matched controls, of whom 176 cases and 663 controls were lifetime nonsmokers. Data on demographic background, reproductive factors and dietary intake of fruit, vegetables and soy foods were obtained by in-person interview. We observed an inverse association between intake of total, cruciferous and non-cruciferous vegetables and risk of lung cancer among smokers. Although smokers in the highest tertile of fruit intake also had a lower risk, this was not statistically significant. Higher intake of soy foods significantly reduced risk of lung cancer among lifetime nonsmokers, but not among smokers. When soy isoflavonoid intake in mg/week was computed based on frequency and portion size of intake of eight common local soy foods, the adjusted OR among nonsmokers for the highest tertile compared to the lowest was 0.56, 95% CI 0.37-0.85 (p for trend <0.01). Fruit intake was also significantly associated with reduced lung cancer risk among nonsmokers, but the effect was not significant after adjustment for soy intake. On the other hand, soy intake remained an independent predictor of risk after controlling for fruit intake. Reproductive effects were also primarily confined to lifetime nonsmokers, among whom having 3 or more livebirths (adjusted OR 0.65, 0.44-0.96) and a menstrual cycle length of more than 30 days (OR 0.46, 0.25-0.84) accorded a significantly reduced risk of lung cancer. Place of birth was significantly associated with risk among nonsmokers (OR 2.6, 1.7-3.9 for China-born vs. local born) but not among smokers. When analysis was restricted to nonsmokers with adenocarcinomas, the dietary effects were consistent or enhanced. On stepwise regression, soy intake and cycle length emerged as the independent dietary and reproductive predictors of lung cancer risk in nonsmokers. These findings are consistent with other evidence suggesting an involvement of estrogen-related pathways in lung cancer among non-smoking women., (Copyright 2001 Wiley-Liss, Inc.)

The Singapore Cancer Registry has provided comprehensive population-based incidence data since 1968. This paper describes the population-based survival analysis of the registry data. All invasive primary cancers diagnosed from January 1, 1968 to December 31, 1992 were passively followed up until December 31, 1997. Only 5.8% were lost to follow-up. Cumulative and observed survival rates were calculated using Hakulinen's method. Overall 5-year relative survival rates have increased dramatically over the 25-year period in both genders. Significant increases are seen with nasopharynx, stomach and colo-rectum cancers, non-Hodgkin's lymphoma, leukemias and cancers of the testis, cervix, ovaries and breast. When compared with the Surveillance, Epidemiology and End Results (SEER) rates in the United States, the 5-year relative survival rates in Singapore are generally lower. However, the rate of change between the two countries is fairly similar. On the average, the rates are 10 to 15 years behind the SEER rates and 5 to 10 years behind Finland, Switzerland and Japan, but they are close to the UK rates. The age-standardized 5-year survival rate for Singapore is higher for most sites compared with other developing countries like Qidong (China), Madras (India), Bombay (India) and Chiang Mai (Thailand). The 25-year trend in cancer survival in Singapore showed two extreme groups: those showing no change and those showing significant improvements. Reducing the incidence of cancers belonging to the first group remains the only viable mode of cancer control. For cancers in the second group, improvement in survival is due to a combination of successful early detection measures and effective treatment services in Singapore., (Copyright 2001 Wiley-Liss, Inc.)

The association between the consumption of preserved foods in infancy, childhood and adulthood and the risk of nasopharyngeal carcinoma was investigated in a case-control study among Singapore Chinese: 200 cases (73% male) were compared with 406 hospital controls (71% male). Significantly increased risks were observed in association with frequent adult consumption of salted soy beans (OR 7.3 for consumption 4 or more times per week, compared with never), canned pickled vegetables (p = 0.01; OR 4.5 for 4 or more times per week), "sze chuan chye", a salted Chinese tuber, (OR 2.4 for 4 or more times per month) and "kiam chye", salted mustard greens (OR 2.7 for 4 or more times per week). A protective effect of high vitamin-E intake in adulthood was observed (OR 0.5 for the highest third of the control range, as compared with the lowest).

Benzene exposure causes leukemia and lymphomas. Recent epidemiological findings have also shown an association between cigarette smoking and an increased risk of leukemia. However, further evidence is required to document the biological plausibility of this association. In evaluating this link, it is important to note that cigarette smoke contains benzene and various pyrolytic compounds, among other carcinogens. This study aims to determine the uptake of benzene by measuring 3 benzene-related compounds in cigarette smokers and non-smokers. Urinary concentrations of catechol (CAT), hydroquinone (HQ), and trans,trans-muconic acid (tt-MA) were measured by high-performance liquid chromatography (HPLC) with fluorimetric and UV detection, respectively. The results showed that these compounds were present in all urine samples. However, the concentrations were significantly higher in smokers than in non-smokers. The mean level of urinary tt-MA was 0.19 +/- 0.09 mg/g creatinine for 46 male smokers and the corresponding value for 40 non-smokers was 0.14 +/- 0.07 mg/g creatinine. The mean concentrations of HQ and CAT were 0.81 +/- 0.4 and 3.51 +/- 2.6 mg/g creatinine for smokers, and 0.45 +/- 0.4 and 1.94 +/- 1.2 mg/g creatinine for non-smokers, respectively. These results suggest that cigarette smoking is associated with a significant additional exposure to benzene and its related compounds. Furthermore, significant correlations were observed between the concentrations of cotinine, the metabolite of nicotine, and the above compounds. These findings suggest that the exposure originated from cigarette smoking.

Since the inception of cancer registration in Singapore in 1968, the incidence rates of malignancies have been monitored among the 3 major ethnic groups--Chinese (77% of population), Malays (15%) and Indians (6%). Substantial changes in incidence at various sites were observed in the period 1968-1982, which seem to represent a shift from the pattern of cancer incidence in China towards that prevailing in the West. We now report on the Singapore Chinese experience, in which the following changes were notable: decreases in rates of cancers of the stomach and oesophagus and increases in rates of cancers of the lung, colon, rectum, skin (excluding melanoma), breast and ovary. For several sites, the secular changes differed among age groups; among women under 50 years of age breast cancer increased particularly sharply and lung cancer decreased. Environmental and personal factors, potentially responsible for the change, are discussed.

A hospital-based case-control study of diet and colorectal cancer was conducted among Chinese in Singapore (who constitute 77% of the population). A total of 203 cases and 425 controls were included. A history of the usual dietary intake one year prior to interview was taken using a quantitative food frequency questionnaire. Daily intakes of nutrients and selected food items were computed and stratified by tertiles of the control range, to assess risk in low-, medium- and high-intake categories. Effects were adjusted in analysis for age, sex, Chinese dialect group and occupation. For cancers of colon and rectum combined, significant observations were a protective effect of high cruciferous vegetable intake (OR = 0.50, p less than 0.01) and a predisposing effect of a high meat/vegetable consumption ratio (OR = 1.77, p less than 0.05). Similar results were observed for colon cancer alone. For rectal cancer alone (only 71 cases), significant (p less than 0.05) protective effects were observed for high intakes of protein (OR = 0.61), fibre (OR = 0.46), beta-carotene (OR = 0.54), cruciferous vegetables (OR = 0.51) and total vegetables (OR = 0.51). When further assessed by multiple logistic regression, tests for trend and assessment of risk in the extreme highest and lowest quintiles of the control range, the factors consistently significant were cruciferous vegetable intake and the meat/vegetable ratio. A particularly high relative risk was also noted in association with low coffee consumption (OR = 1.59, with p less than 0.05 for trend). No consistent trends were noted for fat or fibre intakes. For non-dietary variables investigated, a history of cholecystectomy increased the risk of both cancers combined (OR = 3.43, p less than 0.05) and colon cancer alone (OR = 4.39, p less than 0.01). This study in an Asian population of countries of Southern and Eastern Asia newly undergoing industrialization and in which rapid economic change is reflected in changing cancer patterns, suggests that the protective effects of certain dietary constituents, notably the cruciferous vegetables, may be more important than the hitherto stressed carcinogenic potential of fat and protein.