Essential fatty acids and prostate cancer: an emerging hypothesis?
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Biomedical subjects
Publications and source records attributed to A W Hsing.
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As part of a large-scale, community-based cervical neoplasia screening project in rural Taiwan, a case-control study was undertaken to evaluate the etiologic role of human papillomavirus (HPV) infection in this mainly monogamous (2% reported having multiple sexual partners) female population. A total of 88 biopsy-confirmed cases and 261 cytologically normal controls were selected for the study. The case group included 40 cases of cervical intraepithelial neoplasia (CIN) 1, 9 of CIN 2, 36 of CIN 3 and 3 cases of invasive cancer. Cervical swabs collected at screening from study subjects were tested for HPV DNA by an LI consensus primer polymerase chain reaction (PCR)-based technique. HPV DNA was found in 92% of high-grade cases (CIN 2-3 and invasive cancer); 54% of low-grade cases (CIN 1); and 9% of controls. HPV was significantly associated with both high-grade and low-grade cervical neoplasia. As reported in Western countries, HPV 16 was the predominant type among HPV-positive high-grade cases. However, HPVs 52 and/or 58 combined were the most common types among HPV-positive low-grade cases and controls. Among women without any high-risk HPV infection (types 16, 18, 31 or 45), those with multiple-type HPV infection had a higher risk for high-grade cervical neoplasia than those with single-type infection. Overall, 91% of high-grade cases and 50% of low-grade cases could be attributed to HPV infection. Our results show that, even in this monogamous population, HPV is the major risk factor for high-grade cervical neoplasia.
A population-based cohort of 120 Danish men, discharged with a hospital diagnosis of primary hemochromatosis from 1977 to 1989, was followed up to 1989 for subsequent cancer risk. Nineteen subjects (including 6 with primary liver cancers) were excluded from the analysis, either because they died within the same month of hemochromatosis diagnosis or because they had cancer prior to diagnosis of hemochromatosis. Among the 101 remaining subjects, 4 primary liver cancers occurred one year or more after the diagnosis of hemochromatosis, far surpassing the expected number based on incidence rates from the Danish population (standardized incidence ratio 92.9, 95% confidence interval 25.0 to 237.9). The excess of liver cancer was associated with cirrhosis and included cholangiocarcinoma as well as hepatocellular carcinoma. Significantly elevated risks were also observed for non-hepatic cancers (13 cases; SIR 3.5, 95% CI 1.9 to 6.0), notably esophageal cancer (2 cases; SIR 42.9, 95% CI 4.8 to 154.9) and skin melanoma (2 cases; SIR 27.8, 95% CI 3.1 to 100.3). The results of this population-based study are in accordance with the hypothesis that patients with primary hemochromatosis have a substantial risk of primary liver cancer. Further studies of hemochromatosis may be useful in clarifying the relation of non-hepatic malignancies to body iron stores in the general population.
Based on occupational data for all (n = 264) prostate cancer cases diagnosed during 1980-84 in urban Shanghai and on employment information from the 1982 census, standardized incidence ratios (SIR) were calculated for occupational groups classified by job type and physical activity level. White-collar workers (professionals, government officials, clerical workers, salespersons) had an elevated incidence of prostate cancer, although the excesses were not significant. In addition, when jobs were classified by time spent sitting or energy expenditure, men employed in occupations with low physical activity levels tended to have moderately elevated risks of prostate cancer. Findings from this study in an area with one of the world's lowest incidence rates of prostate cancer add to the accumulating evidence that jobs with a low level of physical activity are associated with an increased prostate-cancer risk.
BACKGROUND: Cervical cancer is the second leading cause of cancer death among Chinese women. Within China, a considerable geographical variation in mortality rates has been observed, but the reasons are not well understood. METHODS: Cervical cancer rates were examined in relation to indices of reproductive factors, dietary habits, and selected serum biomedical markers in 65 rural Chinese counties. RESULTS: Cervical cancer mortality rates correlated positively and significantly with antibodies to herpes simplex virus type 2 (HSV-2) (r = 0.40, P < 0.01), serum levels of ferritin (r = 0.33, P < 0.01), body mass index (BMI) (r = 0.42, P < 0.01) and cigarette smoking (r = 0.51, P < 0.05) and negatively and significantly with age at first birth (r = -0.51, P < 0.01), consumption of green vegetables (r = -0.40, P < 0.01) and animal foods (r = -0.40, P < 0.01), and serum levels of selenium (r = -0.26, P < 0.05). When these variables were considered in the multiple regression analysis, early age at first birth and higher BMI were positively associated with cervical cancer mortality, while consumption of green vegetables and animal foods were negatively correlated. In the serum model, infection with HSV-2 and low levels of sex hormone binding globulin (SHBG) were positively related to cervical cancer mortality. No relation was found for consumption of fruits. CONCLUSIONS: Although limitations of these ecologic data preclude causal inferences, findings in this study, including associations with HSV-2 infection, early age at first birth, consumption of green vegetables and animal foods, may provide clues to cervical cancer aetiology.
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Vasectomy has been reported to be associated with an increased risk of prostate cancer in western countries. A hospital-based case-control study was conducted in 12 cities in China to evaluate the relationship between vasectomy and prostate cancer risk in China, a low-risk country with rising incidence and increasing use of vasectomy. Interviews were conducted with 138 histologically confirmed prostate cancer cases diagnosed during 1989-1992 and 638 controls (158 hospital cancer, 158 hospital noncancer, and 322 neighborhood controls) of similar ages. Vasectomy at least 10 years prior to interview was reported by 10% of the cases versus 3% of the controls. Odds ratios for prostate cancer associated with vasectomy were 2.0 (95% confidence interval, 0.7-6.1), 3.3 (95% confidence interval, 1.0-11.3), and 6.7 (95% confidence interval, 2.1-21.6), respectively, when hospital cancer, hospital noncancer, and neighborhood controls were used for comparison. Although detection bias is of concern, the data suggest that in China, men with a history of vasectomy may experience an increased risk of prostate cancer.
Using the Cancer-Environment Registry of Sweden, which links census information (1960) with cancer incidence data (1961 to 1979), we conducted a systematic, population-based assessment of colon cancer incidence among cohorts defined by industry and occupation for all employed persons in Sweden. Small but statistically significant excesses of colon cancer were observed among white-collar occupations, including administrators, professionals, and clerical and sales workers, whereas a reduction in incidence was found among workers in agricultural and related jobs, such as farmers, fishermen, and hunters. Analysis by subsite within the colon revealed little difference in results. The observed risk patterns are consistent with previous reports on colon cancer risk and occupational physical activity levels, ie, elevated risk among sedentary white-collar workers and reduced risk among agricultural workers. Few craftsman and production processing jobs were linked to colon cancer, although statistically significant excesses were observed among shoe and leather workers, metal smiths, and foundry workers in the metal manufacturing industry. The findings indicate that occupation in general is likely to play a relatively small role in colon cancer etiology, with perhaps its major contribution an indirect one via physical activity.
BACKGROUND: Elevated risk of cancers of the stomach, colon, and buccal cavity, as well as of lymphoma and leukemia, have been reported for patients with pernicious anemia in case reports and hospital-based and cross-sectional studies. METHODS: A cohort of 2021 men and 2496 women living in the Uppsala health care region in Sweden, discharged with a hospital diagnosis of pernicious anemia from 1965 to 1983, was followed for 20 years for subsequent risk of cancer. RESULTS: A total of 553 cancers were diagnosed among these patients, significantly more than expected based on cancer standardized incidence rates (SIRs) in the general population (SIR = 1.4; 95% confidence interval [CI], 1.2-1.5). Most prominent were excesses for cancer of the stomach (SIR = 2.9; 95% CI, 2.4-3.5), esophagus (SIR = 3.2; 95% CI, 1.8-5.2), and pancreas (SIR = 1.7; 95% CI, 1.2-2.4) among men and women; myeloid leukemia among men (SIR = 4.4; 95% CI, 1.8-5.2); and multiple myeloma among women (SIR = 2.5; 95% CI, 1.1-4.9). An excess of gastric carcinoid tumors also was evident in this cohort. The risk of stomach cancer was highest in the first year after diagnosis of pernicious anemia (SIR = 7.4; 95% CI, 5.3-10.1), but an increased risk persisted throughout the follow-up period. The risk of esophageal cancer also remained elevated throughout the study period, although the risk of pancreatic cancer dropped off after 5 years. CONCLUSIONS: This study confirms the excess risk of gastric carcinoma and carcinoid tumors associated with pernicious anemia, and suggests that the susceptibility state may extend to esophageal and other cancers.
Small intestine cancer is relatively rare. Clinical reports have suggested that several medical conditions may predispose to increased occurrence of this cancer, but otherwise its etiology is unknown. In one of the first case-control studies of this cancer, we compared questionnaire responses provided by next-of-kin of 430 persons who died of small intestine cancer cf921 controls who died of other causes. Subjects were identified from decedents included in the 1986 United States National Mortality Followback Survey. The questionnaires sought information on demographic and lifestyle characteristics, including diet and use of tobacco and alcohol. Tobacco and alcohol consumption were unrelated to risk of small intestine cancer, but weekly or more frequent consumption of red meat and monthly or more frequent intake of salt-cured/smoked foods were associated with two- to three fold increases in risk. The findings suggest that dietary factors probably are involved in risk of small intestine cancer, but additional research in other settings is required to clarify the determinants of these rare cancers.
The aim of this study was to determine the risk of developing primary liver cancer in patients with a diagnosis of alcoholism, liver cirrhosis, or both. Three population-based, mutually exclusive cohorts were defined on the basis of hospital discharge diagnosis between 1965 and 1983. Complete follow-up through 1984--excluding the first year of follow-up--showed that among 8,517 patients with a diagnosis of alcoholism, 13 cancers occurred, vs. 4.2 expected (standardized incidence ratio (SIR) = 3.1; 95% confidence interval (CI) = 1.6 to 5.3); among 3,589 patients with liver cirrhosis, 59 cancers occurred, vs. 1.7 expected (SIR = 35.1; 95% CI = 26.7 to 45.3), and among 836 patients with both diagnoses, 11 cancers occurred, vs. 0.3 expected (SIR = 34.3; 95% CI = 17.1 to 61.3). Thus, alcoholism alone entailed a moderately increased risk and alcoholism with liver cirrhosis did not increase the high relative risk for liver cancer more than cirrhosis alone. We conclude that alcohol intake may be a liver carcinogen only by being causally involved in the development of cirrhosis; and further, that the risk of developing liver cancer following cirrhosis in this population is similar to or higher than that after chronic hepatitis-B-virus infection in other Western countries.
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A population-based case-control study of renal pelvis and ureter cancers (502 cases, 496 controls) conducted in three areas of the United States found cigarette smoking to be associated with a 3.1-fold increase in risk, with long-term (greater than 45 years) smokers having a 7.2-fold increased risk. Statistically significant dose-response associations were observed for both cancer sites and in both sexes regardless of the measure used: cigarettes per day, duration of use, or pack years. A significant decreasing trend in risk with increasing years quit smoking was also demonstrated for these cancers. Attributable risk estimates indicate that approximately 7 of 10 cancers of the renal pelvis and ureter among men and almost 4 of 10 among women are caused by smoking. The results of this study, the largest to date, confirm that cigarette smoking is the major cause of cancers of the renal pelvis and ureter, and that cessation of smoking could eliminate a large proportion of these tumors.
The incidence of cancer was studied in a population-based cohort of 9,353 individuals (8,340 men and 1,013 women) with a discharge diagnosis of alcoholism in 1965-83, followed up for 19 years (mean 7.7). After exclusion of cancers in the first year of follow-up, 491 cancers were observed cf 343.2 expected through 1984 (standardized incidence ratio [SIR] = 1.4, 95 percent confidence interval [CI] = 1.3-1.6). A similar excess risk of cancer was seen among men (SIR = 1.4, CI = 1.3-1.6) and among women (SIR = 1.5, CI = 1.1-2.0). We observed the established associations with cancers of the oral cavity and pharynx (SIR = 4.1, CI = 2.9-5.7), esophagus (SIR = 6.8, CI = 4.5-9.9), larynx (SIR = 3.3, CI = 1.7-6.0), and lung (SIR = 2.1, CI = 1.7-2.6), although confounding by smoking likely increased these risk estimates. While there was evidence of increased risk for pancreatic cancer (SIR = 1.5, CI = 0.9-2.3), alcoholism did not elevate the incidence of cancer of the stomach (SIR = 0.9, CI = 6-1.4), large bowel (SIR = 1.1, CI = 0.8-1.5), prostate (SIR = 1.0, CI = 0.8-1.3), urinary bladder (SIR = 1.0, CI = 0.6-1.5), or of malignant melanoma (SIR = 0.9, CI = 0.3-1.9). Among women, the number of breast cancers observed was close to expected (SIR = 1.2, CI = 0.6-2.2), although a significant excess number of cervical cancers occurred (SIR = 4.2, CI = 1.5-9.1).(ABSTRACT TRUNCATED AT 250 WORDS)
The association of oral contraceptive use with liver cancer was examined in a study of 76 deaths from primary liver cancer, 22 deaths from cancer of the intrahepatic bile ducts, and 629 controls among women aged 25 to 49 years. The subjects in the study are from the 1986 National Mortality Followback Survey, which included a questionnaire sent or administered to the next-of-kin of almost 20,000 deceased individuals in the United States. Information on a number of lifestyle factors was collected, including questions on oral contraceptive use. Increased risks of primary liver cancer were found for ever-users (odds ratio [OR] = 1.6, 95 percent confidence interval [CI] = 0.9-2.6), and for long-term (greater than or equal to 10 years) users (OR = 2.0, CI = 0.8-4.8) of oral contraceptives. When the analysis was restricted to subjects whose spouse or parent was the respondent, more pronounced risks were seen for ever-users (OR = 2.7, CI = 1.4-5.3) and long-term users (OR = 4.8, CI = 1.7-14.0). No clear excess risk was found for cancer of the intrahepatic bile ducts. This study, the largest to date, adds to the number of investigations demonstrating an increased risk of primary liver cancer with use, particularly long-term use, of oral contraceptives.
A 26-year follow-up of nearly 250,000 US veterans who responded to a questionnaire revealed 4,607 deaths from prostate cancer, providing the largest number of cases to date for evaluating relation to tobacco habits. Cigarette smokers had a significant increase in relative risk (RR = 1.18; 95% confidence interval 1.09-1.28) and a dose response reaching 1.51 among smokers of 40 or more cigarettes per day. Risks were elevated, but not significantly, among users of smokeless tobacco and pipe/cigar smokers. Despite limited data in the literature to support this finding, our study suggests that cigarette smoking may be related to prostate cancer, perhaps through its effect on sex hormone metabolism.
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.
To provide clues to the causes of liver cancer in China, we studied the correlation of certain dietary and biochemical markers with liver cancer mortality across 65 Chinese counties. Mortality rates were significantly linked to the county-wide prevalence of hepatitis-B surface antigen positivity. Rates were also higher in counties with high plasma levels of total cholesterol and high consumption of liquor, rapeseed oil, and mouldy corn, while inverse associations were observed for wheat consumption. All of the observed associations, except those with cholesterol and rapeseed oil, were more pronounced in men than in women. No significant correlations with liver cancer mortality were found for consumption of several other foods; plasma levels of retinol, beta-carotene, alpha-tocopherol, selenium, zinc and ferritin; or urine levels of aflatoxin B1. Although causal inferences cannot be derived, this ecological study suggests that chronic infection with hepatitis-B virus contributes to the substantial variation in liver cancer mortality in China, and provides leads for further studies into the role of dietary and nutritional determinants.