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R K Ross

Publications and source records attributed to R K Ross.

At least 145 records · Page 8Linked to original sources
PubMed1990

Increased cell division as a cause of human cancer.

Carcinogenesis research is increasingly focused on chemicals that are not genotoxic and yet, at high doses, can induce cancer, apparently by increasing cell proliferation. We hypothesize that increased cell division per se stimulated by external or internal factors is also associated with the development of many human cancers. Although this hypothesis is well substantiated in the experimental literature, it has not been generalized as an important mechanism for carcinogenesis in human populations. Under this increased cell division model, the pathogenesis of cancer may result from molecular genetic errors induced during the process of cell division and from altered growth control of malignant or premalignant cells. Molecular genetic analysis of human cancers has shown that tumor cells contain multiple genetic defects including mutations, translocations, and amplifications of oncogenes and are reduced to homozygosity for putative tumor suppressor genes; these phenomena all require cell division for their occurrence and fixation. Increased cell division increases the risk of such events occurring. An accumulation of a combination of such genetic errors leads to a neoplastic phenotype. Examples are discussed of human cancers in which increased cell division, which drives the accumulation of genetic errors and can lead to neoplastic transformation, is caused by hormones, drugs, infectious agents, chemicals, physical or mechanical trauma, and other chronic irritation.

Animals↗
PubMed1990

Prevalence of hepatitis B and C viral markers in black and white patients with hepatocellular carcinoma in the United States.

The recent cloning of the genome of a non-A, non-B hepatitis agent, designated the hepatitis C virus (HCV), has led to the development of an immunoassay for circulating HCV antibodies (anti-HCV). We used this immunoassay to investigate the possible association between HCV infection and hepatocellular carcinoma in black and white residents of Los Angeles County, California. Serum samples from 51 patients (12 black and 39 white) in Los Angeles County with hepatocellular carcinoma and 128 control subjects (1 black and 127 white) were tested for the presence of anti-HCV. In addition, samples were tested for hepatitis B surface antigen (HBsAg), antibodies to the hepatitis B core antigen (anti-HBc), and antibodies to HBsAg (anti-HBs). Our results indicate that the presence of anti-HCV was a significant risk factor for hepatocellular carcinoma; the relative risk was 10.5 (95% confidence limits = 3.5, 31.3). Hepatocellular carcinoma risk was also significantly related to the presence of one or more of the hepatitis B virus (HBV) markers, primarily HBsAg and anti-HBc, and the relative risk was 7.0 (95% confidence limits = 3.1, 16.1). HCV and HBV independently contributed to hepatocellular carcinoma development. Significantly increased risk of hepatocellular carcinoma was demonstrated in individuals with HCV (relative risk = 4.8) or HBV (relative risk = 4.4) serologic markers alone. A synergistic effect on risk was observed when both hepatitis B and C viral markers were present in peripheral blood (10 cases vs. no controls). We estimate that approximately 47% of hepatocellular carcinoma occurring in black and white residents of Los Angeles County could be attributed to prior HCV and/or HBV infections: 9% were related to HCV alone, 20% to HBV alone, and 18% to occurrence of both HCV and HBV infections.

Antibodies, Viral↗
PubMed1990

Epidemiology of hairy cell leukemia in Los Angeles County.

The descriptive epidemiological characteristics of hairy cell leukemia (HCL), a rare chronic lymphoproliferative disorder, were examined by using incidence data collected from 1972 to 1987 by the Cancer Surveillance Program, the population-based cancer registry for Los Angeles County. During the study period, 208 incident cases of histologically confirmed HCL were diagnosed. HCL comprised 2% of all leukemias diagnosed in Los Angeles County during the study period. HCL risk was concentrated in white males; there were few black and Asian patients for analysis. Overall, the age-adjusted incidence rate of HCL for men (2.9/million population) was 4.8 times greater than that for women (0.6/million population). Using data from all cancer patients diagnosed during the study period, Jewish men had significantly greater risk of HCL than Protestant men (odds ratio (OR) = 3.0, P less than 0.0001); there was no significant variation in risk of HCL by religion for women. For men, the OR was significantly elevated for professional and technical workers (OR = 2.1, P = 0.001); within this category of occupations, risk was significantly elevated for engineers (OR = 3.3, P less than 0.0001) and university faculty and school teachers (OR = 4.0, P = 0.0008). HCL patients were more than twice as likely to have multiple primary cancer diagnoses as other cancer patients. Since the majority of the other primary cancer diagnoses occurred prior to (greater than 1 year) or concurrent with (less than or equal to 1 year) the HCL diagnosis, this greater frequency of multiple primaries in HCL patients may be due to impaired immune function.

Adult↗
PubMed1990

Serum hormone levels in pre-menopausal Chinese women in Shanghai and white women in Los Angeles: results from two breast cancer case-control studies.

To assess whether risk of breast cancer in young women is associated with differences in luteal-phase hormone production and to attempt to explain differences in risk of breast cancer of young Shanghai Chinese and Los Angeles white women, two concurrent case-control studies of serum hormone concentrations were conducted. Both studies were carefully controlled for the possible confounding effects of age, weight, height, pregnancy history, and day of the menstrual cycle, by individually matching cases and controls on these factors. Case eligibility was limited to women with localized breast cancer. Sixteen of 39 Shanghai breast-cancer cases were sampled prior to the histologic diagnosis of their disease. The remaining 23 Shanghai cases and all 42 Los Angeles cases were diagnosed, and treated by surgery only, at least six months prior to hormonal evaluation. All subjects were sampled on day 22 of the menstrual cycle. Overall, cases had 13.5% higher serum estradiol concentrations (p = 0.038) with a case-to-control excess of 16.6% in Shanghai subjects (p = 0.089) and 10.8% in Los Angeles subjects (p = 0.23). There were no appreciable differences in amounts of sex-hormone binding globulin between cases and controls. Cases had lower progesterone levels than controls, but the situation was reversed when the analysis was restricted to subjects with evidence of ovulation. Los Angeles controls had 20.6% greater estradiol concentrations than Shanghai controls (p = 0.036); adjustment for body weight accounted for only 25.7% of this difference.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1990

A prospective study of risk factors for traumatic deaths in a retirement community.

We examined possible predictors of traumatic deaths by means of a case-control study nested within a large ongoing cohort study of residents of a Southern California retirement community. Baseline information was collected by means of a detailed mailed health survey completed by 11,888 residents in 1981-1982. In multivariate logistic regression analysis, being widowed or divorced (RR = 6.4, P = 0.009), sleeping 9 or more hours per night (RR = 4.6, P = 0.02), and drinking more than three alcoholic beverages a day (RR = 3.5, P = 0.04) were significant predictors of suicide risk. However, the strongest predictor of suicide was a mental outlook assessment summary score calculated from responses to seven questions derived from the Zung self-rating depression scale. Individuals in the poorest summary score category were 23 times more likely to commit suicide than individuals in the best summary score category (P = 0.004). Women who regularly practiced breast self-examination were also at very low risk for suicide (RR = 0.1, P = 0.0005). The mental outlook assessment summary score was also a predictor of accidental deaths, although the relative risk estimates were lower than those for suicide and the individual questions best predicting risk were different. A history of a serious chronic disease (RR = 2.6, P = 0.01) and moderate alcohol intake of less than two drinks per day (RR = 0.3, P = 0.01) were also predictors of accidental deaths. Estrogen use in women did not predict risk of traumatic deaths.

Accidents↗
PubMed1990

Serum oestrogen levels in postmenopausal women: comparison of American whites and Japanese in Japan.

Serum oestrone (E1), oestradiol (E2) and sex hormone binding globulin (SHBG) levels were studied in postmenopausal Japanese women in Japan (n = 91) and postmenopausal American white women (n = 38). The Japanese women were deliberately chosen to be from a rural agricultural area in order to get samples which represent as closely as possible the traditional Japanese 'lifestyle' that gave rise to the low rates of breast cancer in Japan. E1 levels were 47%, and E2 levels 36%, greater in the American women; these differences were only reduced to 43% and 27% after adjustment for the lower weight of the Japanese. These results were all statistically highly significant. There was little difference in SHBG levels between the Japanese and the American women. These results for E1 and E2 could be an important part of the explanation why Japanese and American breast cancer rates continue to diverge further after the menopause.

Aged↗
PubMed1990

Hormone levels in older women: a study of post-menopausal breast cancer patients and healthy population controls.

Hormone concentrations in blood and total 12 h urine values were compared between 40 post-menopausal women with breast cancer and 40 control women in a study which carefully controlled for the possible confounding effects of age, weight and pregnancy history by individually matching cases and controls on these factors. Breast cancer cases had received only surgical treatment for their localised disease, which was diagnosed from 1 to 9 years before hormonal evaluation. Cases had 15% higher serum oestradiol levels (P = 0.02), 40% more urinary oestradiol (P = 0.03) and 44% more urinary oestriol (P = 0.04) than control women. Cases also had higher levels of serum and urinary oestrone, but these differences were not statistically significant. The percentages of serum oestradiol not bound to albumin or sex-hormone binding globulin did not differ between cases and controls, nor were there statistically significant differences in the serum levels of prolactin, sex-hormone binding globulin or dehydroepiandrosterone sulphate. These results provide further support for the hypothesis that breast cancer risk is determined in part by post-menopausal serum oestrogen concentration.

Aged↗
PubMed1989

Risks and benefits of long-term treatment with estrogens.

The goal of contemporary hormone replacement is to minimize net predictable lifetime risk; success therefore depends upon quantitative assessments of the net quality of life, of net morbidity and of net mortality. Estrogens ameliorate menopausal symptoms, maintain bone integrity, and produce endometrial cancer; these facts and their quantitative aspects can be stimulated. Other links are gradually becoming clear: estrogens increase biliary disease, but prevent heart disease, and, it now seems, stroke. Conventional wisdom to the contrary notwithstanding, a critical review suggests that breast cancer is probably increased in frequency by long-term estrogen use; the increase is modest as a risk factor but because breast cancer is a common disease, it is substantial in absolute terms. The addition of progestin seems attractive as a method of opposing undesirable estrogenic effects on the endometrium. In fact, there is reason for concern about the effect of an added progestin upon the risks from breast cancer, heart disease, and stroke; even the magnitude of the expected reduction in endometrial cancer may not be great when the hormone is administered sequentially. Using a simple deterministic model of post-menopausal life with hormone replacement, we have inserted available estimates of the regimen-specific relative risk for each outcome, and translated each net impact into common denominators of morbidity and mortality. While estrogens probably increase net morbidity, as measured by either the number of hospitalizations to be anticipated or by the more arbitrary measure of expected days of disability, these negative changes are mostly due to gallbladder disease and endometrial cancer, both largely treatable conditions. Largely because of protection against heart disease, estrogen replacement in modest dose is likely to reduce substantially the number of deaths to be expected in women treated through age 75 and even into more advanced age. Hormone replacement which includes systemic progestin supplementation has not been empirically tested; it may be beneficial, but it is at least as likely to be harmful. Either a modest increment in the number of additional breast cancers produced by estrogens, a modest reduction in the number of cardiac events prevented by estrogens, or a simultaneous minor shift in the same direction for each condition, would have the effect of shifting the net reduction in cumulative deaths into an increase in the number of deaths as a result of treatment.(ABSTRACT TRUNCATED AT 400 WORDS)

Aged↗
PubMed1989

Aspirin use and chronic diseases: a cohort study of the elderly.

OBJECTIVE: To evaluate the associations between the use of aspirin and the incidences of cardiovascular diseases, cancers, and other chronic diseases. DESIGN: Postal questionnaire survey to elicit details of aspirin use. SETTING: Californian retirement community. SUBJECTS: All 22,781 residents of the community (white, affluent, and well educated) were sent a questionnaire that included questions on medical history and the use of drugs such as analgesics, laxatives, and vitamin supplements. In all 61% responded (13,987, 8881 women and 5106 men; median age 73). They formed the cohort that was followed up for 6 1/2 years using discharge summaries from three hospitals serving the area and death certificates from the health department. Only 13 respondents were lost to follow up but seemed not to have died. MAIN OUTCOME MEASURES: Incidences of cardiovascular diseases, cancers, gastrointestinal bleeding, ulcers, and cataracts were compared in participants who did and did not take aspirin daily. RESULTS: Age adjusted incidences were computed with an internal standard and five age groups. By 1 January 1988 there had been 25 incident cases of kidney cancer among all participants; 341 incident cases of stroke, 253 of acute myocardial infarction, 220 of ischaemic heart disease, and 317 of other heart disease were reported among respondents without a reported history of angina, myocardial infarction, or stroke. The incidence of kidney cancer was raised among those who took aspirin daily compared with those who did not take it, although the increase was significant only in men (relative risks = 6.3, 95% confidence interval 2.2 to 17, for men and 2.1, 0.53 to 8.5, for women). Those who took aspirin daily showed no increased risk of any other cancer, except colon cancer for both sexes combined (relative risk = 1.5, 1.1 to 2.2). The risk of acute myocardial infarction was reduced slightly among regular users of aspirin in men but not women. The risk of ischaemic heart disease was almost doubled in those who took aspirin daily compared with non-users (relative risks = 1.9, 1.1 to 3.1, for men and 1.7, 1.1 to 2.7, for women). Small, non-significant increased risks of stroke were observed in both sexes. CONCLUSION: The daily use of aspirin increased the risk of kidney cancer and ischaemic heart disease.

Aged↗
PubMed1989

Analgesics, cigarette smoking, and other risk factors for cancer of the renal pelvis and ureter.

Results from a population-based case-control study of cancer of the renal pelvis and ureter are reported. Telephone interviews were conducted with 187 residents of Los Angeles County diagnosed with cancer of the renal pelvis and ureter over a 4-year period ending December 31, 1982, and with individually sex-, age- and race-matched neighborhood controls. The major risk factor identified for cancer of the renal pelvis and ureter was cigarette smoking. Subjects who smoked more than 25 years had a relative risk of 4.5 of developing these tumors, compared to nonsmokers (P less than 0.0001). Heavy use of over-the-counter analgesics was also associated with a significant increase in risk; it appears that an elevated risk was conveyed by all the major active constituents of those compounds currently marketed in the United States, aspirin, caffeine, and acetaminophen. Persons who had used these drugs for 30 consecutive days at any time in their life preceding diagnosis had twice the risk of developing cancer of the renal pelvis or ureter compared to persons not reporting such use (P less than 0.01). Heavy coffee drinkers (greater than or equal to 7 cups/day) had a 1.8-fold increase in risk compared to nondrinkers. Although risk tended to increase with increasing consumption, this result was not statistically significant. The risk associated with heavy coffee consumption was reduced to 1.3 after adjusting for smoking. Nine cases compared to no controls reported a first degree relative with kidney cancer. A history of kidney stones was associated with an increased risk of cancer of the ureter (relative risk = 2.5) that was not, however, statistically significant.

Analgesics↗
PubMed1989

AIDS-related secular trends in cancer in Los Angeles County men: a comparison by marital status.

Data from the population-based cancer registry for Los Angeles County, an area with high risk of AIDS, were used to evaluate secular trends of Kaposi's sarcoma (KS), non-Hodgkin's lymphoma, and other possibly AIDS-related cancers in men aged 18 to 54. Marital status was used as a surrogate for homosexual behavior to compare the proportional incidence rates for the pre-AIDS era, 1972 to 1979, to those for 1980 to 1982 and 1983 to 1985. Both absolute incidence and proportional incidence of KS continue to increase sharply, although in absolute numbers, KS is making a smaller contribution to the total number of AIDS cases as the Los Angeles County epidemic progresses. For never-married men the proportional incidence rate of KS in 1983 to 1985 was nearly 100-fold greater than that of 1972 to 1979 and 7-fold greater than that of 1980 to 1982. High-grade lymphomas show statistically significant secular increases in both never-married and ever-married men, but only the rates of Burkitt's lymphomas have increased to a greater extent in never-married men. A small but significant increase of central nervous system lymphomas is seen in both marital status groups. There is no evidence of any AIDS-related increases in Hodgkin's disease, leukemia, testicular cancer, anal cancer, liver cancer, oral cancer, multiple myeloma, or malignant melanoma. As of 1985, cancer, as a manifestation of AIDS, is still apparently limited to KS and high-grade lymphomas (particularly Burkitt's) in Los Angeles County.

Acquired Immunodeficiency Syndrome↗
PubMed1989

Cardiovascular benefits of estrogen replacement therapy.

Epidemiologic case-study and cohort-study data concerning effects of estrogen replacement therapy on the risk of cardiovascular disease in postmenopausal women are reviewed. Although there is conflicting literature, most research strongly suggests that estrogens, and estrogen replacement therapy in particular, reduce the risk of cardiovascular disease. Such reduced risk in estrogen users is most likely mediated in part by the beneficial effects of estrogen therapy on lipid metabolism. Risks associated with the use of estrogens and possible effects when progestational agents are added to an estrogen regimen are also discussed.

Breast Neoplasms↗
PubMed1989

LHRH agonists and the prevention of breast and ovarian cancer.

Early age at natural menopause or bilateral ovariectomy substantially reduce a woman's lifetime risk of breast cancer. Reversible 'bilateral ovariectomy' can now in effect be achieved by 'high-dose' luteinising hormone releasing hormone (LHRH) agonists (LHRHAs). The harmful effects of such medical reversible bilateral ovariectomy, in particular the increased risks of coronary heart disease and osteoporosis, can in all likelihood be obviated by 'low-dose' oestrogen replacement therapy (ERT), specifically 0.625 mg of conjugated equine oestrogens (CEE) for 21 days in each 28-day treatment cycle, and such ERT use will only negate to a relatively small extent the beneficial effect of such bilateral ovariectomy on breast cancer risk. We calculate that such an LHRHA plus low-dose ERT regimen given to a premenopausal woman for 10 years will, in addition to being a most effective contraceptive, decrease her lifetime risk of breast cancer by more than 50%. We calculate that such a 10-year regimen will also decrease her risk of ovarian cancer by two-thirds. This regimen should leave endometrial cancer risk and bone metabolism unaltered, and may reduce the risk of heart disease. The addition of a 'low-dose' progestogen to the regimen for 12 days in each 28-day treatment cycle would be beneficial to the endometrium, but it will adversely affect risk factors for heart disease and it may significantly reduce the benefit of the regimen as regards breast cancer. A satisfactory compromise may be to add a low-dose progestogen for 12 days at less frequent intervals. Another possibility may be to deliver a progestogen solely to the endometrium with an intra-uterine device; the benefits of such a regimen would be a significant reduction in the incidence of breast, ovarian and endometrial cancer.

Breast Neoplasms↗
PubMed1989

Endometrial cancer and patterns of use of oestrogen replacement therapy: a cohort study.

5,160 non-hysterectomised women aged 44-100 years completed a health survey questionnaire as part of a longitudinal study of a southern California retirement community begun in June 1981. As of 1 January 1987, 50 incident cancers of the endometrium had occurred among these women, who had contributed 23,786 years of follow-up. Women who had used oestrogen replacement therapy had a relative risk of endometrial cancer of 10 compared to women who had never used oestrogens (P less than 0.0001). Risk increased with increasing duration of use (chi 2 test for trend = 50.60, P less than 0.0001); women who had used oestrogens for 15 or more years had a relative risk of 20 (95% C.I. = 7.2, 54) compared to non-users. While current and recent users (i.e. those who had used oestrogen within one year of the initial survey) had the greatest risk (RR = 25, 95% C.I. = 9.2, 69), women who had last used oestrogens 15 or more years ago still had a significantly increased risk (RR = 5.8, 95% C.I. = 2.0, 17). No other variable studied had a major effect on risk, except smoking. Women who smoked at the time of menopause had a significantly reduced risk of disease (RR = 0.38, P = 0.005), which was essentially unchanged after adjustment for oestrogen use.

Adult↗
PubMed1989

Cigarette smoking in pregnancy results in marked decrease in maternal hCG and oestradiol levels.

We have examined serum levels of oestradiol (E2), sex-hormone binding globulin (SHBG) and human chorionic gonadotrophin (hCG) during early pregnancy in relation to smoking status at the time of sampling in a series of 147 women. Smoking was associated with significantly depressed serum levels of E2, SHBG and hCG: in smokers, E2 levels were on average 17.6% lower (P = 0.037), SHBG levels were 12.4% lower (P = 0.15), and hCG levels were 21.5% lower (P = 0.044). There appeared to be a steady decline in these values with increasing cigarette consumption. These lower hormone levels in smokers may explain certain adverse effects of smoking in pregnancy.

Adult↗