Evidence for an important role of alcohol- and aldehyde-metabolizing genes in cancers of the upper aerodigestive tract.

BACKGROUND: Incidence and mortality rates of upper aerodigestive tract cancers in Central Europe are among the highest in the world and have increased substantially in recent years. This increase is likely to be due to patterns of alcohol and tobacco consumption. Genetic susceptibility to upper aerodigestive tract cancer in relation to such exposures is an important aspect that should be investigated among populations in this region. METHODS: A multicenter case-control study comprising 811 upper aerodigestive tract cancer cases and 1,083 controls was conducted in: Bucharest (Romania), Lodz (Poland), Moscow (Russia), Banska Bystrika (Slovakia), and Olomouc and Prague (Czech Republic). We analyzed six SNPs in three genes related to ethanol metabolism: alcohol dehydrogenase 1B and 1C (ADH1B, ADH1C) and aldehyde dehydrogenase 2 (ALDH2). RESULTS: The ADH1B histidine allele at codon 48 was associated with a decreased risk of upper aerodigestive tract cancer; odds ratios (OR) were 0.36 [95% confidence interval (95% CI), 0.17-0.77] for medium/heavy drinkers and 0.57 (95% CI, 0.36-0.91) for never/light drinkers. Moderately increased risks were observed for the ADH1C (350)Val allele (OR, 1.19; 95% CI, 0.98-1.55) and ADH1C (272)Gln allele (OR, 1.24; 95% CI, 0.98-1.55). Medium/heavy drinkers who were heterozygous or homozygous at ALDH2 nucleotide position 248 were at a significantly increased risk of upper aerodigestive tract cancer (OR, 1.76; 95% CI, 1.13-2.75; OR, 5.79; 95% CI, 1.49-22.5, respectively), with a significant dose response for carrying variant alleles (P = 0.0007). Similar results were observed for the ALDH2 +82A>G and ALDH2 -261C>T polymorphisms. When results were analyzed by subsite, strong main effects were observed for squamous cell carcinoma of the esophagus for all six variants. Among the 30% of the population who were carriers of at least one ALDH2 variant, the attributable fraction among carriers (AF(c)) was 24.2% (5.7-38.3%) for all upper aerodigestive tract cancers, increasing to 58.7% (41.2-71.0%) for esophageal cancer. Among carriers who drank alcohol at least thrice to four times a week, the AF(c) for having at least one ALDH2 variant was 49% (21.3-66.8%) for all upper aerodigestive tract cancers, increasing to 68.9% (42.9-83.1%) for esophageal cancer. CONCLUSIONS: Polymorphisms in the ADH1B and ALDH2 genes are associated with upper aerodigestive tract cancer in Central European populations and interact substantially with alcohol consumption.     

Alcohol drinking, cigarette smoking, and the development of squamous cell carcinoma of the esophagus: epidemiology, clinical findings, and prevention

Both cigarette smoking and alcohol drinking are well-established risk factors for esophageal squamous cell carcinoma (ESCC), and the relationship of dose to cancer risk has already been described. Furthermore, the synergistic effect of these two factors has been reported. Our case–control study revealed the odds ratio of ESCC to be 50.1 for those who were both heavy smokers and heavy drinkers in comparison to people who neither drank nor smoked. In patients with ESCC, head and neck cancers as well as dysplastic lesions are frequently observed. Heavy smoking and heavy drinking are closely related to such multicentric carcinogenesis events in the upper aerodigestive tract (UADT), including the esophagus and head andneck region. Polymorphisms in acetaldehyde dehydrogenase 2 (ALDH2) are reported to be a key event in deciding individual susceptibility to UADT cancer. Patients with inactive ALDH2, in whom facial flushing is usually observed after the drinking of alcohol, are at high risk for ESCC as well as multiple UADT cancers. For the early detection of the disease, effective follow up using endoscopy with Lugol staining or narrow band imaging endoscopy is strongly recommended for high-risk populations, such as smokers, heavy drinkers, people with experience of flushing after the drinking of alcohol, and patients with UADT cancer.     

Pipe smoking and cancers of the upper digestive tract

Pipe smoking has been related to the risk of cancers of the upper digestive and respiratory tract, but quantification of the risk for exclusive pipe smokers is still limited. To analyse the association between exclusive pipe smoking and cancers of the upper digestive tract, we used data from a series of case-control studies conducted in Italy and Switzerland between 1984 and 1999. After excluding cigarette and cigar smokers, 41 male oral and pharyngeal cancer cases, 52 male oesophageal cancer cases and 1,032 male controls were included in the present analysis. Odds ratios (OR) of cancers were estimated by the mean of unconditional multivariate logistic regression, including terms for age, study centre, education, body mass index, and alcohol drinking. Compared to never smokers, exclusive pipe smokers had an OR of 8.7 [95% confidence intervals (CI): 4.0-18.9] of all upper digestive tract cancers. The OR was 12.6 for oral and pharyngeal and 7.2 for oesophageal cancer. Pipe smokers who were also heavy alcohol drinkers had an OR of 38.8 (95% CI: 13.6-110.9) as compared to never smokers and light drinkers. Thus, pipe smoking and heavy alcohol drinking appears to interact at least on a multiplicative model.     

Lifetime risk of distinct upper aerodigestive tract cancers and consumption of alcohol,betel and cigarette

The cancer of upper aerodigestive tract (UADT) is a common cancers in the world. However, its lifetime risk by consumption of alcohol, betel and cigarettes remain to be elucidated. This study aimed to estimate lifetime risk of distinct UADT cancers and assess their associations with alcohol, betel and cigarette consumption. Three cohorts of 25,611 men were enrolled in 1982–1992 in Taiwan. The history of alcohol, betel and cigarette consumption was enquired through questionnaire interview. Newly developed UADT cancers were ascertained through computerized linkage with national cancer registry profile. Lifetime (30–80 years old) risk and multivariate‐adjusted hazard ratio (HR_adj) of distinct UADT cancers by alcohol, betel and cigarette consumption were estimated. A total of 269 pathologically confirmed cases of UADT cancers were newly‐diagnosed during 472,096 person‐years of follow‐up. The lifetime risk of UADT cancer was 9.42 and 1.65% for betel chewers and nonchewers, 3.22 and 1.21% for cigarette smokers and nonsmokers and 4.77 and 1.85% for alcohol drinkers and nondrinkers. The HR_adj (95% confidence interval) of developing UADT cancer was 3.36 (2.51–4.49), 2.02 (1.43–2.84), 1.90 (1.46–2.49), respectively, for the consumption of betel, cigarette and alcohol. Alcohol, betel and cigarette had different effect on cancers at various anatomical sites of UADT. The cancer risk from the mouth, pharynx, esophagus to larynx increased for alcohol and cigarette consumption, but decreased for betel consumption. Alcohol, betel and cigarette consumption are independent risk predictors for distinct UADT cancers.     

Effect of cigarette smoking and alcohol consumption in the etiology of cancers of the digestive tract

This study presents the comparative patterns of risk of selected digestive tract cancers (esophagus, stomach, colon, rectum and liver) for males in relation to cigarette smoking and alcohol drinking, based on the data from case-control studies conducted in the Korea Cancer Center Hospital (KCCH). There was strong positive association between cigarette smoking and esophageal cancer, but none of the other sites was significantly related to cigarette smoking. In esophageal cancer, a dose-dependent effect for cigarette smoking was observed, with the odds ratio ranging from 1.29 for ever smoking up to 1 pack daily to 3.17 for smokers of more than 2 packs per day. The risk declined markedly following cessation of smoking. Cancers of the esophagus, rectum and liver were strongly related to alcohol consumption. Compared with non-drinkers, the OR for heavy drinkers was 9.14 in esophageal cancer, 4.75 in rectal cancer and 2.46 in liver cancer. In cancer of the stomach and colon, however, there was no association with alcohol drinking.     

Dietary risk factors for upper aerodigestive tract cancers

We examined the association between whole-grain intake and incident upper aerodigestive tract cancer in a cohort of 34,651 postmenopausal, initially cancer-free women. We also studied established risk factors for upper aerodigestive cancers, including fruit and vegetable intake, smoking and alcohol intake. A mailed questionnaire at baseline in 1986 included a food-frequency questionnaire and assessment of other cancer risk factors. During the 14-year follow-up period, 169 women developed cancer of the upper aerodigestive tract. For all upper aerodigestive cancers together, significant inverse associations were observed for the highest compared to the lowest tertile of whole grains [relative risk (RR) = 0.53, 95% confidence interval (CI) 0.34-0.81] and yellow/orange vegetables (RR = 0.58, 95% CI 0.39-0.87). In addition, those in the highest compared to lowest tertile of fiber intake from whole grain were less likely to develop upper aerodigestive tract cancer (RR = 0.56, 95% CI 0.37-0.84); fiber intake from refined grain was not significantly associated with upper aerodigestive tract cancer. Findings were generally similar for oropharyngeal (n = 53), laryngeal (n = 21), nasopharyngeal/salivary (n = 18), esophageal (n = 21) and gastric (n = 56) cancers, though numbers of cases were too small for statistical testing within individual cancers. These findings confirm previous observations that high intake of fruits and vegetables and that intake of whole grains and the fiber derived from them may reduce risk of upper aerodigestive tract cancers.     

An epidemiologic study of thyroid cancer in Hawaii

A population-based case-control interview study was designed to test the hypothesis that dietary iodine or the consumption of goitrogenic vegetables increases the risk of thyroid cancer. A total of 191 histologically confirmed cases (64 percent female) and 441 matched controls from five ethnic groups in Hawaii were available for analysis. Among women, intake of seafood (especially shellfish), harm ha (a fermented fish sauce), and dietary iodine were associated with an increased risk of cancer, whereas consumption of goitrogenic (primarily cruciferous) vegetables was associated with a decreased risk. Non-dietary risk factors included miscarriage (especially at first pregnancy), use of fertility drugs, family history of thyroid disease, obesity, and work as a farm laborer. The odds ratio for the combined effect of a high iodine intake and a first-pregnancy miscarriage was 4.8 (95 percent confidence interval [CI]=1.2 – 19.2); and for high iodine intake and use of fertility drugs 7.3 (95 percent CI=1.5 – 34.5). Among men, positive associations were found for obesity, work as a farm laborer, and a past history of benign thyroid disease. Although this study identified several dietary and non-dietary risk factors for thyroid cancer, it could not fully explain the exceptionally high incidence rates among Filipino women in Hawaii.Drs Kolonel, Hankin, and Wilkens are in the Epidemiology Program, Cancer Research Center, University of Hawaii. Dr Fukunaga is at the Kuakini Medical Center, Honolulu, HI, USA. Dr Hinds was with the Epidemiology Program at the time of this work and is now with the Snobomish Health District, Everett, WA, USA. Address correspondence to Dr Kolonel at 1236 Lauhala Street, Room 407, Honolulu, HI 96813, USA. This work was supported in part by grant no. 1 PO1 33619 and contract no. N01 CN 55424 from the National Cancer Institute, US Department of Health and Human Services.     

Effects of alpha-tocopherol and beta-carotene supplementation on upper aerodigestive tract cancers in a large, randomized controlled trial

BACKGROUND: Although smoking and alcohol consumption are the major risk factors for upper aerodigestive tract cancers, observational studies indicate a protective role for fruits, vegetables, and antioxidant nutrients. METHODS: The authors examined whether daily supplementation with 50 mg dl alpha-tocopheryl acetate and/or 20 mg beta-carotene reduced the incidence of or mortality from oral/pharyngeal, esophageal, and laryngeal cancers in the Alpha-Tocopherol, Beta-Carotene Cancer Prevention (ATBC) study, a double-blind, placebo-controlled primary prevention trial conducted in southwestern Finland. A total of 29,133 male smokers, aged 50-69 years and free of cancer at baseline, were randomized in a 2 x 2 factorial design to the supplementation regimen for 5-8 years (median, 6.1 years). Incident cancers of the oral cavity and pharynx (n = 65), esophagus (n = 24), and larynx (n = 56) were identified through the Finnish Cancer Registry. Intervention effects were assessed using survival analysis and proportional hazards models. RESULTS: There was no effect of either agent on the overall incidence of any upper aerodigestive tract cancer. For larynx, however, exploratory subgroup analyses were suggestive of a protective effect of beta-carotene supplementation on the incidence of early stage malignancies (stage I, relative risk [RR], 0.28, 95% confidence interval [CI]: 0.10-0.75). Neither agent affected mortality from these neoplasms. CONCLUSIONS: The results do not provide support for a protective effect of vitamin E or beta-carotene supplementation on upper aerodigestive tract cancers, although beta-carotene supplementation may impact the incidence of some subtypes of laryngeal tumors.     

Coffee and green tea consumption is associated with upper aerodigestive tract cancer in Japan

The impact of coffee and green tea consumption on upper aerodigestive tract (UADT) cancer risk has not been established. Evaluation of the possible anticarcinogenic properties of their ingredients is confounded by the potential increase in risk owing to the high temperatures at which these beverages are generally consumed. We conducted a case–control study to evaluate the association between coffee and tea consumption and the risk of UADT cancer. The study enrolled 961 patients with UADT cancer and 2,883 noncancer outpatients who visited Aichi Cancer Center between 2001 and 2005. Information on coffee and green tea consumption and other lifestyle factors was collected via a self‐administered questionnaire. Consumption of three or more cups of coffee per day had a significant inverse association with UADT cancer [odds ratio (OR) 0.73, 95% confidence interval (CI) 0.55–0.96]. In contrast, consumption of three or more cups of green tea per day had a significant positive association with UADT cancer (OR 1.39, 95% CI 1.13–1.70). These associations were evident for head and neck cancer but not for esophageal cancer. The association of coffee consumption with head and neck cancer was observed only among never smokers and alcohol drinkers. Similarly, the association of green tea consumption was observed among never smokers and never alcohol drinkers. No change in these associations was seen on stratification by each confounding factors. These findings suggest that consumption of coffee might be associated with a decreased risk of UADT cancer, whereas that of green tea might be associated with an increased risk.     

Familial upper aerodigestive tract cancers: incidence trends,familial clustering and subsequent cancers

Familial risks in upper aerodigestive tract cancer have been assessed mainly through case-control studies based on reported but not medically verified cancers in family members. The nationwide Swedish Family-Cancer Database was used to describe the incidence trends for all subsites of upper aerodigestive tract cancer and to calculate standardized incidence ratios (SIRs) and 95% confidence intervals (CIs) for the cancer in 0-66-year-old offspring by cancers in family members. Additionally, SIRs for second primary cancer after upper aerodigestive tract cancers were analysed. SIRs in offspring for all upper aerodigestive tract cancer were not significant when a parent presented with concordant cancer. The population attributable fraction of familial upper aerodigestive tract cancer was 0.43%. Risk for subsequent cancers in men and women after upper aerodigestive tract cancer were increased in smoking, alcohol and other life-style related sites and in skin cancer and non-Hodgkin's lymphoma.     

Alcohol and tobacco, and the risk of cancers of the upper aerodigestive tract in Latin America: a case�Ccontrol study

Background

Cancers of the upper aerodigestive tract (UADT; including oral cavity, pharynx, larynx and oesophagus) have high incidence rates all over the world, and they are especially frequent in some parts of Latin America. However, the data on the role of the major risk factors in these areas are still limited.

Methods

We have evaluated the role of alcohol and tobacco consumption, based on 2,252 upper aerodigestive squamous-cell carcinoma cases and 1,707 controls from seven centres in Brazil, Argentina, and Cuba.

Results

We show that alcohol drinkers have a risk of UADT cancers that is up to five times higher than that of never-drinkers. A very strong effect of aperitifs and spirits as compared to other alcohol types was observed, with the ORs reaching 12.76 (CI 5.37?C30.32) for oesophagus. Tobacco smokers were up to six times more likely to develop aerodigestive cancers than never-smokers, with the ORs reaching 11.14 (7.72?C16.08) among current smokers for hypopharynx and larynx cancer. There was a trend for a decrease in risk after quitting alcohol drinking or tobacco smoking for all sites. The interactive effect of alcohol and tobacco was more than multiplicative. In this study, 65% of all UADT cases were attributable to a combined effect of alcohol and tobacco use.

Conclusions

In this largest study on UADT cancer in Latin America, we have shown for the first time that a prevailing majority of UADT cancer cases is due to a combined effect of alcohol and tobacco use and could be prevented by quitting the use of either of these two agents.     

Multiple occurrence of carcinoma in the upper aerodigestive tract associated with esophageal cancer: Reference to smoking,drinking and family history

Smoking and drinking habits as well as family history were examined in 143 men with esophageal cancer, including 30 who had associated second cancers of the upper aerodigestive tract (UADT) and 113 who did not. The risk of second cancers of UADT associated with the main lesions of the esophagus was evaluated, using odds ratios (ORs). As a result, the ORs of second cancers for current smoking and drinking were 5.3 and 7.6 respectively. The ORs significantly increased to 12.7 and 14.7 in heavy smokers and in heavy drinkers respectively. Furthermore, the risk of second cancer also significantly increased (8-fold) in patients who had close relatives with UADT cancer, compared to those without family history of any cancer. However, there were no differences in smoking or drinking habits regardless of family history. Our data thus suggest that a family history of UADT cancer as well as heavy smoking and drinking are clearly associated with multiple occurrence of UADT cancer. Therefore, careful and frequent examination for appearance of any second lesions are required for patients in these high-risk groups.     

Hepatitis B virus, cigarette smoking and alcohol consumption in the development of hepatocellular carcinoma: a case-control study in Fukuoka, Japan.

The roles of the hepatitis B virus (HBV), cigarette smoking and alcohol consumption in the etiology of hepatocellular carcinoma (HCC) were examined in a case-control study involving 204 patients with HCC and 410 control subjects in Fukuoka prefecture, where HCC risk is among the highest in Japan. Information on smoking and drinking habits was obtained by a detailed interview survey, and the results were analyzed in conjunction with serum hepatitis B surface antigen (HBsAg) status after adjustment for sex, age and other possible confounding factors. Individuals positive for serum HBsAg showed a relative risk (RR) for HCC of 13.8 (95% confidence interval, Cl 5.9 to 32.5), whereas heavy drinkers experienced about a 2-fold risk increase compared with non-drinkers. Light or moderate drinkers, however, demonstrated RRs near the unity. Some risk excess was observed among ex-smokers (RR = 1.5, 95% CI 0.8 to 2.8) and current smokers (RR = 1.5, 0.8 to 2.7) compared with non-smokers, but without evidence for a dose-response relationship in terms of pack-years. Analysis among HBsAg-negative subjects revealed similar non-significant association with smoking, and there was no clear interaction between alcohol and cigarette consumption on HCC risk. Other significant risk factors included positive histories of blood transfusion (RR = 3.7, 2.2 to 6.3) and familiar liver disease (RR = 2.6, 1.6 to 4.2). Attributable risk calculations suggest that chronic HBV infection and heavy drinking may account for 17% and 13% of HCC occurrence, respectively, in this high risk area. The association of cigarette smoking with HCC was not evident in our study.     

The aetiology of upper aerodigestive tract cancers among young adults in Europe: the ARCAGE study

Background

The incidence of cancers of the upper aerodigestive tract (UADT) is increasing throughout the world. To date the increases have been proportionally greatest among young people. Several reports have suggested that they often do not have a history of tobacco smoking or heavy alcohol consumption.

Objective

To determine the contribution of lifestyle factors to the etiology of UADT cancers occurring in those aged less than 50 years.

Methods

A case–control study was conducted in 10 European countries. Cases were cancers of the oral cavity and pharynx, larynx and esophagus, and hospital or population controls were age and sex matched.

Results

There were 356 cases younger than 50 years and 419 controls. Risk was strongly related to current smoking [odds ratio (OR) 5.5 95%; confidence interval (CI) (3.3, 9.2)], and risk increased with number of pack-years smoked. Risk was also related to alcohol consumption for both current (OR 1.8; 0.97, 3.3) and past (OR 3.4; 1.6, 7.4) drinkers, and risk increased with number of drink-years. Persons frequently consuming fruits and vegetables were at significantly reduced risk.

Conclusions

Risk factors already identified as being important for UADT cancers in adults are also important influences on risk in younger adults. The implication of these results is that the public health message in preventing UADT cancers remains the same to young and old alike.     

Cancer morbidity and causes of death among Danish brewery workers.

Cancer morbidity and causes of death were examined in a retrospective cohort study of 14,313 male members of the Danish Brewery Workers' Union in order to determine health effects of heavy beer drinking, in particular in the aetiology of colorectal cancer. Brewery workers hold the right to consume 6 bottles (2,100 ml) of light pilsener beer (alcohol content 3.7 g1/00 ml) on the premises of the brewery per working day. The cohort included 1,063 mineral-water factory workers with no free ration of beer. Cancer morbidity and mortality were compared with those of the general population after adjustment for age, sex, area and time trends. Cancer morbidity, 1943–1972, was increased for cancer of the pharynx (RR = 2.09), oesophagus (RR=2.09), liver (RR=1.51) and larynx (RR = 1.98). The risk of these tumours was highest among workers who had had a ration of free beer during 30 or more years of employment. An increased risk of lung cancer (RR-1.16) corresponds with the risk among persons of low socio-economic class. These tumour sites accounted for a 9% excess of all malignant neoplasms among members of the BWU. No increased risk for either cancer of the colon (RR = 1.07) or cancer of the rectum (RR = 1.02) was observed. In contrast to studies on “alcoholics”, only deaths from the above-mentioned cancers, liver cirrhosis (RR=1.77) and motor vehicle accidents (RR = 1.33) were in excess; total mortality was only slightly above expectation (RR = 1.06). The present investigation suggests that the statistical association between beer and colo-rectal cancer is of a non-causal nature. It is concluded that the heavy consumption of “weak” alcoholic beverages may increase the risk of upper aero-digestive tract cancers, and that part of the disease pattern associated with “alcoholism” is unrelated to alcohol consumption.     

Temporal relationship between cancers of the lung and upper aerodigestive tract

We retrospectively reviewed the chart records at the Veterans General Hospital-Taipei for the period between January 1985 and December 1994 to examine the temporal relationship between cancers of the lung and upper aerodigestive tract. A total of 56 patients (54 males, 2 females) with histocytologically proven double primary cancers, with either lung cancer or upper aerodigestive tract cancers appearing first, were found. Squamous cell carcinoma was the most frequent histologic type of lung cancer (squamous 57%, adenocarcinoma 27%, poorly differentiated carcinoma 9%, small cell lung cancer 7%). The incidence of lung cancer patients with upper aerodigestive tract cancer was 0.9% (56/6412). There was no significant difference in the occurrence of upper aerodigestive tract cancer between non-small cell and small cell lung cancer (P > 0.05). However, the incidence of squamous cell lung cancer with upper aerodigestive tract cancer was higher than that of non-squamous cell lung cancer (P < 0.05). With regard to the location of lung cancer, the right lung was more commonly affected than the left (P < 0.001). The locations of upper aerodigestive tract cancers in these lung cancer patients were as follows: larynx 24, nasopharynx 11, esophagus 10, hypopharynx 4, pharyngeal tonsils 2, oral cavity 5. Most upper aerodigestive tract cancers were diagnosed before lung cancer (36/56, 64%), and lung cancer was diagnosed within 3 years in more than half of cases after the diagnosis of upper aerodigestive tract cancer (58.3%). Most lung cancers that preceded upper aerodigestive tract cancer were at an early stage at diagnosis (stage I 4, stage Illa 1), whereas the others, appearing either synchronously or after the diagnosis of upper aerodigestive tract cancer, were mostly at the late stage. There was no difference in survival between lung cancer patients with upper aerodigestive tract cancer and those without (P > 0.05).      

Cigarette smoking and leukemia: results from the Lutheran Brotherhood Cohort Study

In a 20-year follow-up (1966–86) of 17,633 White males who described tobacco use in a mailed questionnaire sent in 1966, there were 74 deaths from leukemia (including 30 myeloid, 30 lymphatic, and 14 other and unspecified leukemia). Among men who ever smoked cigarettes, increased risks were observed for lymphatic (relative risk [RR]=2.7), and other and unspecified leukemia (RR=1.5); risks rose with increasing number of cigarettes smoked, although the dose-response relationship was statistically significant only for total leukemia. Mortality from myeloid leukemia was not elevated, except among those smoking over a pack of cigarettes per day. Results from this cohort support a relationship between cigarette smoking and leukemia. Further studies are needed to elucidate subtype associations with cigarette smoking.Drs Linet, McLaughlin, Hsing, Wacholder, and Blot are with the Epidemiology and Biostatistics Program, National Cancer Institute. Dr Co-Chien is at Westat, Inc., Rockville, Maryland, USA, Dr Schuman is at the University of Minnesota, Minneapolis, Minnesota, USA. Dr Bjelke is with the Center for Epidemiologic Research, University of Bergen, Norway. Address correspondence to Dr Linet, Epidemiology and Biostatistics Program, National Cancer Institute, Executive Plaza North Room 415B, Bethesda, MD 20892, USA.     

Risk factors for multicentric occurrence of carcinoma in the upper aerodigestive tract-analysis with a serial histologic evaluation of the whole resected-esophagus including carcinoma

BACKGROUND AND OBJECTIVES: We have reported that both lifestyle and family history might be related to multiplicity of carcinoma in the upper aerodigestive tract (UADT). The aim of this study was to elucidate the relationship between the number of carcinomas and risk factors. METHODS: A serial histologic evaluation of the entire non-irradiated esophagus was performed in 114 males with esophageal cancer who were divided into three groups (group I: 88 cases with solitary cancer, group II: 11 with double cancers, group III: 15 with three or more cancers). As controls, 228 males with benign diseases were selected. RESULTS: Among group III patients, both the incidence of heavy smoking and that of heavy drinking were 67% and 60%, which were significantly higher than those of group I (28% and 30%) and control subjects (14% and 10%, respectively). Heavy drinkers who were also heavy smokers were observed in 2, 10, 27, and 47% in control subjects, groups I, II, and III, respectively. Regarding family history, 27% of group III had a close relative with UADT or lung cancer, while the incidence was 7% in the control. CONCLUSIONS: These findings strongly support the hypothesis that heavy smoking and heavy drinking, as well as a family history of both UADT and lung cancer, might be risk factors for multicentric occurrence of UADT cancer.     

Cigarette and alcohol consumption and the risk of colorectal cancer in Shanghai, China.

The relation of cigarette smoking and alcohol drinking to colorectal cancer risk has been inconsistent in the epidemiological literature. In a population-based case-control study of colorectal cancer in Shanghai, China, where the incidence rates are rising sharply, we examined the association with tobacco and alcohol use. Cases were aged 30-74 years and newly diagnosed with cancers of the colon (N = 931) or rectum (N = 874) between 1990 and 1992. Controls (N = 1552) were randomly selected among Shanghai residents, frequency-matched to cases by gender and age. Information on lifetime consumption of tobacco and alcohol, as well as demographic and other risk factors, was obtained through in-person interviews. Associations with cigarette smoking and alcohol use were estimated by odds ratios (ORs) and 95% confidence intervals (CIs). Among women, the prevalence of smoking and alcohol drinking was low, and no significant association with colon or rectal cancer was observed. Although cigarette smoking among men was not related overall to colon or rectal cancer risk, there was a 50% excess risk of rectal cancer (OR 1.5, 95% CI 0.9-2.5) among those who smoked 55 or more pack-years. Among men, former alcohol drinkers had an increased risk of colon cancer (OR 2.3, 95% CI 1.4-3.7) but not rectal cancer, while current drinkers had a 30-50% excess risk of colon cancer only among those with long-term (30+ years) and heavy (>560 g ethanol/week) consumption. The excess risks were mainly associated with hard liquor consumption, with no material difference in risk between proximal and distal colon cancer. Although cigarette smoking and alcohol drinking in general were not risk factors for colorectal cancers in Shanghai, there were small excess risks for rectal cancer among heavy smokers and colon cancer among heavy drinkers.     

Cancer risks in men who had children with different partners from the Swedish Family-Cancer Database.

We used the nation-wide Swedish Family-Cancer Database to analyse cancer risks in men who had had children with more than one woman. Cancer cases were retrieved from the Swedish Cancer Registry from years 1961-1998. A total of 2.9 million men and 298,134 cancer cases were covered. For men having children with two, three or more women, increasing risk trends were shown for upper aerodigestive tract, lung, urinary bladder and oesophageal cancers. Decreasing trends were observed for tumours of the colon, skin (squamous cell and melanoma), nervous system and endocrine glands and against myeloma and non-Hodgkin's lymphoma. The present results indicated that men who had had children with multiple women showed an excess of smoking- and alcohol consumption-related cancers. The decreased risks for colon cancer, non-Hodgkin's lymphoma and melanoma were possibly related to lifestyle factors connected with economic deprivation, less obesity and physical fitness. These ill-defined protected factors may be a challenge to epidemiological studies.