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Genetic variants in alcohol dehydrogenase-1B (ADH1B) and aldehyde dehydrogenase-2 (ALDH2) genes modulate acetaldehyde removal upon alcohol ingestion. Although these genetic vulnerabilities have been linked to higher esophageal squamous cell carcinoma (ESCC) risks, it is unclear whether they also determine the time of malignancy presentation. The purpose of this investigation was to unravel genotoxic effects of the two alcohol-metabolizing genes with regard to alcohol and tobacco consumption on the age at ESCC diagnosis and tumor dissemination. ADH1B/ALDH2 genotyping was performed on lymphocyte DNA specimens taken from 406 consecutively registered incident patients with pathology-proven ESCC. To fully utilize individual genetic and survival information, survival analyses and gene-longevity applied approaches were introduced. Among heavy drinkers, the ADH1B Arg/Arg (55 years) and ALDH2 Glu/Lys genotypes (54 years) were found to confer a 15 and 16 years earlier carcinoma diagnosed age than His/His and Glu/Glu nondrinkers (both 70 years), respectively. For drinkers, 1-year age advancement was, separately, associated with a 0.977 and 0.953-fold stepwise reduced likelihood of being ADH1B Arg homozygote and ALDH2 Lys variant. Noticeably elevated hazard-ratio (HR) for drinkers of ADH1B slow-form genotype and ALDH2 inactive-form allele were identified in smokers (HR 5 2.3-2.6), but no in nonsmokers. In smokers, appreciably higher cumulative cancer onset risks were correspondingly recognized from the age of 45 and 49 upward among any 1 Lys allele and Arg/Arg 1 Glu/Glu combined-ADH1B/ALDH2-genotype drinkers than nondrinkers. In conclusion, consumption of tobacco and alcohol, coupled with genetic susceptibilities associated with acetaldehyde elimination, as modulated by ADH1B and ALDH2 genotypes, determines a substantial magnitude of tumorigenetic effect on earlier age ESCC diagnosis. ' 2009 UICC Key words: age factor; alcohol drinking; alcohol dehydrogenase; aldehyde dehydrogenase; areca; esophageal neoplasms; smoking Carcinoma stemming from the esophagus ranks as the eighth most common cancer in the world and is one of the deadliest and, yet, most neglected forms of cancer.1 Given the insidious nature of this neoplasm, it has been found that more than 50% of the eventual patients already have unresectable and/or metastatic conditions at the time of tumor presentation.2 Although recent advances in the diagnosis, staging and treatment of esophageal cancer have brought about noteworthy improvement toward some manner of survival, 75% of the patients still die within 1 year of diagnosis, and currently just 5-14% of such patients survive at least 5 years.2,3 Due, in part, to the high case fatality rate, younger esophageal carcinoma onset has been linked to a shorter life expectancy. This leads to a number of challenging health-related issues for the respective family, as well as to substantial work productivity losses for the country.Alcohol intake is a well-recognized determinant for squamous cell carcinoma (SCC) of the esopha...

The possible association between the risk of rectal cancer and hardness levels in drinking water from municipal supplies was investigated in a matched case-control study in Taiwan. All eligible rectal cancer deaths (986 cases) of Taiwan residents from 1990 through 1994 were compared with deaths from other causes (986 controls), and the hardness levels of the drinking water used by these residents were determined. Data on water hardness throughout Taiwan were collected from Taiwan Water Supply Corporation (TWSC). The control group consisted of people who died from other causes and the controls were pair matched to the cases by sex, year of birth, and year of death. The results show a significant negative relationship between drinking water hardness and rectal cancer mortality. Odds ratio and 95% confidence intervals were 1.24 (1.01-1. 55) and 1.38 (1.10-1.73), respectively, for exposure to moderately hard water and soft water compared with the use of hard water. Trend analyses showed an increasing odds ratio for rectal cancer with decreasing levels of hardness in drinking water. This is an important finding for the Taiwan water industry and human health.

Cervical cancer screening guidelines do not comprehensively define what constitutes high risk. This study developed and validated simple risk-scoring schemes to improve Papanicolaou smear screening for women at high risk. Four cumulative risk score (CRS) schemes were derived respectively for the development of cervical intraepithelial neoplasia grade 1 (CIN1) and grade 2 or worse (CIN21) using community-based case-control data (n 5 1523). By calculating the area under the receiver operating characteristic (AU-ROC) curve, these schemes were validated in a Papanicolaou smear follow-up cohort (n 5 967) and a hospital-based cytology screening population (n 5 217). A high DNA load of high-risk human papillomavirus (HR-HPV) was the main predictor for CIN1 and CIN21, although age, married status combined with the number of sexual partners, active and passive smoking and age at sexual debut also affected associated lesions. In the training set, only the HPVtesting-contained CIN21 CRS scheme presented an excellent discrimination for identifying CIN21 (AU-ROC 5 0.866). Using a CRS cutoff value of 4 to identify CIN21, the sensitivity and specificity of predicting CIN21 for the 3-and 5-year follow-ups were 100% and 90.8%, and 83.3% and 90.4%, respectively, in the validation cohort. In the hospital-based validation population, the CRS scheme showed comparable discrimination for CIN21 detection (sensitivity 88.2% and specificity 84.6%). Women with CRS 4 had a 5.4% and 9.1% of 3-and 5-year cumulative incidence, respectively, and a 40.5-fold hazard ratio of developing CIN21. In conclusion, combined with HR-HPV testing and verified risk factors, a simple CRS scheme could effectively improve the implementation of CIN21 screening.Carcinoma of the cervix uteri was the third most common malignancy and the fourth leading cause of cancer death in women worldwide in 2008.1 In low-resource countries, this neoplasm is the principal cause of cancer deaths among women aged 30 to 50 years.2 Prevention efforts for this carcinoma have centered on screening and detecting women at risk using Papanicolaou cytologic examinations of cervical cells and treating related premalignant lesions. In countries with wide screening coverage at frequent intervals, the incidence of invasive cervical cancer has decreased appreciably.3 However, in many countries-particularly low-and middle-income developing countriesexisting programs resulted in limited benefits to morbidity and mortality of this cancer.4,5 A low cytologic screening rate (estimated at 19%, on average) has been specified as a major reason for this unsuccessful public health care in these areas. 5,6 Recent studies have reported that poor women with higher exposure to smoking, unsafe sex and other cervical cancer risk factors are less likely to receive effective screening.

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