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R K Ross

Publications and source records attributed to R K Ross.

At least 37 records · Page 2Linked to original sources
PubMed2000

Effect of hormone replacement therapy on breast cancer risk: estrogen versus estrogen plus progestin.

BACKGROUND: Hormone replacement therapy (HRT) given as unopposed estrogen replacement therapy (ERT) gained widespread popularity in the United States in the 1960s and 1970s. Recent prescribing practices have favored combination HRT (CHRT), i.e., adding a progestin to estrogen for the entire monthly cycle (continuous combined replacement therapy [CCRT]) or a part of the cycle (sequential estrogen plus progestin therapy [SEPRT]). Few data exist on the association between CHRT and breast cancer risk. We determined the effects of CHRT on a woman's risk of developing breast cancer in a population-based, case-control study. METHODS: Case subjects included those with incident breast cancers diagnosed over 4(1/2) years in Los Angeles County, CA, in the late 1980s and 1990s. Control subjects were neighborhood residents who were individually matched to case subjects on age and race. Case subjects and control subjects were interviewed in person to collect information on known breast cancer risk factors as well as on HRT use. Information on 1897 postmenopausal case subjects and on 1637 postmenopausal control subjects aged 55-72 years who had not undergone a simple hysterectomy was analyzed. Breast cancer risks associated with the various types of HRT were estimated as odds ratios (ORs) after adjusting simultaneously for the different forms of HRT and for known risk factors of breast cancer. All P values are two-sided. RESULTS: HRT was associated with a 10% higher breast cancer risk for each 5 years of use (OR(5) = 1.10; 95% confidence interval [CI] = 1.02-1.18). Risk was substantially higher for CHRT use (OR(5) = 1.24; 95% CI = 1.07-1.45) than for ERT use (OR(5) = 1. 06; 95% CI = 0.97-1.15). Risk estimates were higher for SEPRT (OR(5) = 1.38; 95% CI = 1.13-1.68) than for CCRT (OR(5) = 1.09; 95% CI = 0. 88-1.35), but this difference was not statistically significant. CONCLUSIONS: This study provides strong evidence that the addition of a progestin to HRT enhances markedly the risk of breast cancer relative to estrogen use alone. These findings have important implications for the risk-benefit equation for HRT in women using CHRT.

Aged↗
PubMed2000

Susceptibility to prostate cancer: interaction between genotypes at the androgen receptor and prostate-specific antigen loci.

The androgen receptor (AR) regulates gene transcription by binding to androgen response elements in target gene promoters. The prostate-specific antigen (PSA) gene has a polymorphic androgen response element sequence with two alleles, A and G. We hypothesize that allelic differences in AR-driven PSA expression may influence prostate cancer risk. To test this hypothesis, we assayed PSA genotype for 57 prostate cancer cases and 156 controls from our previous pilot study in which prostate cancer risk was associated with the AR "CAG-short" genotype. Odds ratios (ORs) were estimated relating prostate cancer risk to AR and PSA genotypes, singly and in combination. Subjects with the PSA GG genotype were at significantly increased risk for advanced, but not for localized, prostate cancer (OR, 2.90; 95% confidence interval, 1.24-6.78). When cross-classifying subjects by AR and PSA genotypes, subjects with either a CAG-short allele (and not PSA GG) or with the PSA GG genotype (and not CAG-short) had a modest, statistically insignificant increase in prostate cancer risk overall. However, subjects with both a short CAG allele and PSA genotype GG had a more than 5-fold increase in prostate cancer risk (OR, 5.08; 95% confidence interval, 1.59-16.25). All of the ORs were substantially greater for advanced prostate cancer. Studies with larger numbers of advanced cases will be needed to confirm these results. These results indicate that polymorphism in the PSA gene promoter influences prostate cancer risk, and that the allelic variation in promoter activity may be androgen-dependent. Furthermore, these results support a multigenic etiology for prostate cancer.

Aged↗
PubMed2000

Preserved foods in relation to risk of nasopharyngeal carcinoma in Shanghai, China.

A population-based case-control study was conducted in Shanghai, China, to investigate the association between dietary factors and risk of nasopharyngeal carcinoma (NPC). The study included 935 NPC patients aged 15 to 74 years and 1,032 community controls. Exposures to salted fish and other protein-containing preserved food were associated with increased risk of NPC. Individuals who ate salted fish at least once a week had an 80% increase in risk of NPC relative to those who ate salted fish less than once a month (p = 0.07). Compared with those in the lowest quartile of protein-containing preserved foods, subjects in the highest quartile of intake experienced a statistically significant 78% increase in risk of NPC [odds ratio (OR) = 1.78, 95% confidence interval (CI) = 1.37-2.31], with a dose-dependent relationship (p for linear trend < 0.001 ). A similar association between intake of preserved vegetables and NPC risk was observed (OR = 1.39, p for linear trend = 0.003). In contrast, high intake of oranges/tangerines was associated with a statistically significant reduction in risk of NPC (OR = 0.55, p for linear trend < 0.001). When we examined the joint effect of preserved food and oranges/tangerines on risk of NPC, subjects in the highest tertile of preserved food and the lowest tertile of orange/ tangerine intake had a 3-fold increase in risk (95% CI = 2.08-4.91) compared with those in the lowest tertile of preserved food and the highest tertile of orange/tangerine intake.

Adolescent↗
PubMed2000

Non-dietary risk factors for nasopharyngeal carcinoma in Shanghai, China.

A population-based case-control study was conducted in Shanghai, China, to investigate the associations between exposures to various non-dietary variables and risk of nasopharyngeal carcinoma (NPC). A total of 935 NPC patients and 1,032 community controls were included. Active cigarette smoking was a moderate risk factor for NPC [odds ratio (OR) = 1.28, 95% confidence interval (CI) 1.02-1.61]. Results were highly consistent between men and women. It is estimated that 12% of NPC cases in Shanghai, China, can be attributable to cigarette smoking. Among lifelong nonsmokers, there was a strong and statistically significant positive association between NPC risk and exposure to substantial secondhand smoke as a child or as an adult in women. However, the associations among lifelong nonsmoking men were weaker and not statistically significant. The gender differences in risk associated with passive smoking were either statistically significant or almost so. There were excess numbers of NPC patients compared with control subjects who had a history of chronic ear and nose disease (OR = 1.96, 95% CI 1.56-2.46) and a family history of NPC (OR = 7.47, 95% CI 2.14-12.88).

Adolescent↗
PubMed2000

Inhibition of p160-mediated coactivation with increasing androgen receptor polyglutamine length.

Normal polymorphic size variation of the exon 1 CAG microsatellite of the androgen receptor (AR) is associated with prostate cancer, benign prostatic hyperplasia and male infertility. Furthermore, abnormal expansion of the satellite leads to Kennedy's disease. We have shown recently that the AR N-terminal domain (NTD), which contains the polyglutamine (polyQ) stretch (encoded by the CAG repeat), functionally interacts with the C-termini of p160 coactivators. In the present study we explored possible AR CAG size effects on the p160 coactivator-mediated transactivation activity of the receptor. First, we mapped the p160 coactivator interaction on the AR NTD and found an interaction surface between amino acids 351 and 537. Although this region is 'downstream' from the polyQ stretch, it is still within the AR NTD, is implicated in constitutive transactivation activity of the receptor, and thus might be subject to polyQ size modulation. Indeed, cotrans- fection experiments in cultured prostate epithelial cells, using AR constructs of varying CAG sizes and p160 coactivator expression vectors, revealed that increased polyQ length, up to a size of 42 repeats, inhibited both basal and coactivator-mediated AR transactivation activity. AR expression in these cells, on the other hand, was unaffected by the same increased CAG repeat size range. We conclude that the AR NTD contributes to AR transactivation activity via functional interactions with p160 coactivators and that increasing polyQ length negatively affects p160-mediated coactivation of the AR. This molecular mechanism thus might explain, at least in part, the observed phenotypic effects of the AR CAG size polymorphism.

Androgen Receptor Antagonists↗
PubMed2000

Non-steroidal anti-inflammatory drugs and bladder cancer prevention.

Inclusion of phenacetin among 'proven' human carcinogens by the IARC in 1987, raised concerns about the carcinogenic potential of acetaminophen, its major metabolite. Acetaminophen has been implicated as a possible causal agent in the development of cancer of the renal pelvis. The bladder and renal pelvis, which derive from the same embryological structure, share the same transitional type of epithelium. Past studies have been inconclusive on the possible relationship among these analgesics and bladder cancer but no large, highly detailed study of this association has been conducted. A population-based case-control study conducted in Los Angeles, California, involved 1514 incident bladder cancer cases and an equal number of controls who were matched to the index cases by sex, date of birth (within 5 years) and race. Detailed information on medication use and prior medical conditions was collected through in-person interviews. Regular use of analgesics was not associated with an increased risk of bladder cancer in either men or women. In fact, compared with non- or irregular users, regular analgesic users were at a decreased risk of bladder cancer overall (odds ratio (OR) = 0.81, 95% confidence interval (CI) = 0.68-0.96). However, there were clear differences in both the direction and strength of the associations between the different formulation classes of analgesics and bladder cancer risk. Intake of phenacetin was positively related to bladder cancer risk in a dose-dependent manner while intake of its major metabolite in humans, acetaminophen, was unrelated to risk. Intake of all classes of NSAIDs, except pyrazolon derivatives, were negatively associated with bladder cancer risk, with suggestive evidence that the protective effect varies in strength by subcategories of formulation. Acetic acids seemed to exhibit the strongest protective effect, whereas aspirin/other salicylic acids and oxicam showed the weakest protection.

Adult↗
PubMed2000

Elevated mortality rates from circulatory disease in African American men and women of Los Angeles County, California--a possible genetic susceptibility?

OBJECTIVE: Reports of higher mortality in African Americans have often focused on socioeconomic differences. Such differences do not explain the excess mortality in African Americans compared with Hispanics in Los Angeles County. We suggest the existence of genetic factors to explain at least some of the differences in mortality risk. METHODS: We compared the mortality rates from circulatory diseases in African American and Hispanic adults of Los Angeles County for 1988 to 1992 with the frequency of the angiotensin-converting enzyme (ACE) genotype. RESULTS: African American adults 45 to 74 years old had a 2-fold higher overall mortality rate than Hispanics. The largest differences were seen for hypertensive disease and cardiomyopathy in men; the most striking differences were seen in the youngest age group. Rates were lower in women than in men, but African American women also showed substantial excess compared with Hispanics. ACE genotype also showed a significant difference between the Hispanic and African American population; the latter had a significantly higher prevalence of the DD genotype, which is associated with a higher level of circulating enzyme, and lower prevalence of the II genotype, which is associated with a lower enzyme level. CONCLUSION: African American adults aged 45 to 74 years in Los Angeles County have a substantial excess mortality from hypertensive diseases compared with a similar Hispanic population. The frequency of the ACE DD genotype was higher in African Americans than in Hispanics. These studies may indirectly support the possibility of a genetic contribution to the excess hypertensive disease mortality in African Americans.

Aged↗
PubMed2000

Epidemiology of hepatocellular carcinoma.

Although rare in Canada and the United States, hepatocellular carcinoma (HCC) ranks as the eighth most common cancer in the world. High-risk regions are East and Southeast Asia, and sub-Saharan Africa. Independent of race and geography, rates in men are at least two to three times those in women; this sex ratio is more pronounced in high-risk regions. Rates of HCC in the United States have increased by 70% over the past two decades. Registry data in Canada and Western Europe show similar trends. In contrast, the incidence of HCC in Singapore and Shanghai, China, both high-risk regions, has declined steadily over the past two decades. Among white and black Americans, there is an inverse relationship between social class status and HCC incidence. Chronic infection by the hepatitis B virus (HBV) is by far the most important risk factor for HCC in humans. It is estimated that 80% of HCC worldwide is etiologically associated with HBV. In the United States, although the infection rate in the general population is low, HBV is estimated to account for one in four cases of HCC among non-Asians. Chronic infection by the hepatitis C virus is another important risk factor for HCC in the United States; however, this virus is believed to play a relatively minor role in the development of HCC in Africa and Asia. Dietary aflatoxin exposure is an important codeterminant of HCC risk in Africa and parts of Asia. In Canada and the United States, excessive alcohol intake, cigarette smoking and oral contraceptive use in women also are risk factors for HCC.

Africa South of the Sahara↗
PubMed2000

Declining cancer rates in the 1990s.

PURPOSE: To provide evidence of a substantial decline in cancer rates for the period 1991 through 1995 and characterize major risk factors that seem to be driving secular trends in cancer mortality and incidence. DESIGN: Incidence and mortality rates were calculated using national surveillance data collected through the Surveillance, Epidemiology, and End Results (SEER) program and the National Center for Health Statistics. RESULTS: All-sites cancer incidence and mortality fell in the period 1991 through 1995; this decline is largely attributable to decreases in the smoking-related cancers, especially lung cancer. Of the 20 leading incident cancers today, both incidence and mortality are decreasing among 11 sites for men and 12 for women. In men, the decline in mortality has been notable and is especially apparent for the smoking-related cancers, including those of the lung, oral cavity and pharynx, larynx, and, to a lesser extent, bladder. In women, all-sites mortality decreased only approximately 0.4% from 1991 through 1995. Three cancers continued to show substantial increases in mortality through 1995 for both men and women (liver, multiple myeloma, and non-Hodgkin's lymphoma), while incidence rates continued to climb for liver cancer, non-Hodgkin's lymphoma, and melanoma. CONCLUSION: Data from the SEER program on recent trends in cancer incidence and mortality show that cancer rates are generally on the decline, largely because of reductions in smoking-related cancers. A consistent increase in mortality rates due to liver cancer poses a new health care challenge, one that will require the development of an effective treatment for individuals currently infected with hepatitis C or B to prevent mortality rates from continuing to increase.

Female↗
PubMed2000

N-acetyltransferase 2 phenotype but not NAT1*10 genotype affects aminobiphenyl-hemoglobin adduct levels.

Aminobiphenyls (ABPs) in tobacco have been implicated in bladder cancer etiology in smokers. N-Acetylation of ABPs in the liver, predominantly by the N-acetyltransferase 2 (NAT2) isozyme, represents a detoxification pathway, whereas O-acetylation of N-hydroxy-ABPs in the bladder, predominantly by the N-acetyltransferase 1 (NAT1) isozyme, represents a bioactivation pathway. We and others have demonstrated that NAT2 phenotype affects 3- and 4-ABP-hemoglobin adduct levels (higher levels in slow acetylators), which are considered valid biomarkers of the internal dose of ABP to the bladder. We have also shown that NAT1 genotype (NAT1*10 allele) is associated with increased DNA adduct levels in urothelial tissue and higher risk of bladder cancer among smokers. It is not known whether NAT1*10 genotype influences ABP-hemoglobin adduct levels. Therefore, we assessed 403 primarily non-Hispanic white residents of Los Angeles County for their NAT2 acetylator phenotype, NAT1*10 acetylator genotype, and 3- and 4-ABP-hemoglobin adduct levels. Eighty-two subjects were current tobacco smokers of varying intensities. Tobacco smokers had significantly higher mean 3- and 4-ABP-hemoglobin adduct levels relative to nonsmokers. The levels increased with increased amounts smoked per day (two-sided, P < 0.0001 in all cases). With adjustment for NAT1 genotype and race, the smoking-adjusted geometric mean level of 3-ABP-hemoglobin adducts in NAT2 slow acetylators was 47% higher than that in NAT2 rapid acetylators (P = 0.01). The comparable value for 4-ABP-hemoglobin adducts was 17% (P = 0.02). In contrast, no association between NAT1*10 genotype and 3- or 4 ABP-hemoglobin adduct levels was observed after adjustment for NAT2 phenotype, smoking, and race. The present study suggests that the impact of the NAT1*10 genotype on 3- and 4-ABP-hemoglobin adducts is noninformative on the possible association between NAT1 activity and bladder cancer risk.

Acetylation↗
PubMed2000

Body size, physical activity, and breast cancer hormone receptor status: results from two case-control studies.

We evaluated whether our previous reports of increased postmenopausal breast cancer risk with higher body mass index (BMI) or of reduced premenopausal and postmenopausal breast cancer risk with higher physical activity levels varied according to the tumor's estrogen receptor (ER) and progesterone receptor (PR) status. Participants enrolled in either of two population-based case-control studies in Los Angeles County, California: one of premenopausal women (ages < or = 40 years), and one of postmenopausal women (ages 55-64 years). Case participants were diagnosed for the first time with in situ or invasive breast cancer from 7/1/83 through 12/31/88 (premenopausal women) or from 3/1/87 through 12/31/89 (postmenopausal women). Joint ER/PR status was collected for 424 premenopausal and 760 postmenopausal case participants. The analysis included 714 premenopausal and 1091 postmenopausal age-matched, race-matched (white or Hispanic), parity-matched (premenopausal women only), and residential neighborhood-matched control participants. Among the postmenopausal women, obesity was associated with an increased odds of ER+/PR+ breast cancer (odds ratio, 2.45 for women in the highest versus the lowest body mass index quartile; 95% confidence interval, 1.73-3.47). Body mass index was associated with neither ER-/PR- tumors among the postmenopausal women nor with any ER/PR subgroup among the premenopausal women. For both premenopausal and postmenopausal women, higher recreational physical activity levels (> or = 17.6 MET-hours/week versus no activity) were associated with a 30-60% reduction in risk of nearly all ER/PR subtypes, although the associations were generally of borderline statistical significance. Examining these potentially modifiable breast cancer risk factors by tumor ER and PR status may provide us with greater insight into breast cancer etiology and the mechanisms underlying the risk factor associations.

Adult↗
PubMed2000

CYP1A1 I462V genetic polymorphism and lung cancer risk in a cohort of men in Shanghai, China.

Cytochrome P450 (CYP) CYP1A1 activates tobacco-related carcinogens. A point mutation at codon 462 in exon 7 of CYP1A1 results in a substitution of isoleucine by valine near the heme binding site. This mutation is rare in Caucasians but common in Japanese populations, in which association with increased risk of lung cancer has been reported. There are few data in other Asian populations. We investigated this I462V polymorphism using DNA from 214 incident cases of lung cancer and 669 controls in a prospective cohort study of 18,244 middle-aged and older men in Shanghai, China. The valine allele frequency was 0.138 among the control population. The I462V genotype was not appreciably associated with lung cancer risk overall. There was some suggestion that having at least one valine allele might be related to increased risk of lung cancer among smokers of <20 cigarettes/day (odds ratio, 1.72; 95% confidence interval, 0.82-3.62), particularly among those with homozygous deletion of GSTM1 (odds ratio, 2.80; 95% confidence interval, 1.07-7.33), which is involved in the detoxification of activated tobacco carcinogens. In this Chinese cohort, with CYP1A1 valine allele frequency intermediate between Japanese and Caucasian populations, the I462V polymorphism is not related to lung cancer overall, but it might play a role at lower levels of cigarette smoking among subjects with impaired carcinogen detoxification as assessed by the GSTM1-null genotype.

Benzo(a)pyrene↗
PubMed2000

Precancerous lesions in the kidney.

Renal cell carcinoma (RCC), although occurring less frequently than prostate and bladder cancer, is actually the most malignant urologic disease, killing >35% of affected patients. Therefore, investigation of the nature of premalignant lesions of the kidney is a relevant issue. Following the most recent histological classification RCC can be subdivided into four categories: conventional RCC; papillary RCC; chromophobe RCC; and collecting duct carcinoma. In contrast to many genitourinary malignancies, premalignant alterations in the kidney are scarcely described. Intratubular epithelial dysplasia has been recognized as the most common precursor of RCC. In analogy to prostatic intraepithelial neoplasia (PIN), the premalignant lesions of the kidney are described as high or low-grade renal intratubular neoplasia. In contrast, precancerous lesions have been described as part of the von Hippel-Lindau syndrome (VHL) where the evolution from a simple cyst to an atypical cyst with epithelial hyperplasia to cystic or solid conventional-type RCC is well documented. Finally, in the genesis of papillary RCC an adenoma-carcinoma sequence has been recognized with specific genetic changes. There are no data on the epidemiology of premalignant lesions of the kidney, but research into the etiology of RCC has been extended substantially. Familial and genetic factors are well documented in VHL disease, in hereditary papillary RCC, in the tuberous sclerosis complex and in familial RCC. Cigarette smoking and obesity are established risk factors for RCC. Hypertension or its medication has also been associated with an increased risk. Among dietary factors an inverse relation between risk and consumption of vegetables and fruit has been found. Occupational exposure to substances such as asbestos and solvents has been linked to an increased risk of RCC. Specific RCC variants have distinctive chromosome alterations and several genes have been implicated in the development of RCC. Loss of material from the 3p chromosome characterizes conventional RCC and the deletion of the VHL suppressor gene plays an important role in the genesis of this RCC variant. In contrast, numerical changes with trisomy of chromosomes 7 and 17 and loss of the sex chromosome are typical changes in papillary tumors, whereas papillary RCC have additional trisomies. Chromophobe RCC is characterized by loss of chromosomes with a combination of monosomies. Less consistent genetic alterations are associated with collecting duct carcinoma. The traditional treatment of RCC is surgery by radical or partial nephrectomy. The latter approach carries a risk of tumor recurrence as a result of unrecognized satellite lesions or premalignant lesions that might have been present at the time of surgery. However, the reported recurrence rates after partial nephrectomy are <1% and therefore the possible presence of premalignant disease does not alter the actual treatment strategy advocated. Although multifocality and bilateral occurrence of RCC are much more likely in cases of papillary RCC, biopsy of the renal remnant or contralateral kidney is not justified even in patients with this tumor type. Conversely, patients with RIN in a partial or radical nephrectomy specimen or in a renal biopsy taken for whatever reason should be subjected to closer follow-up with regularly repeated ultrasound. When an effective chemopreventive regimen becomes available it might be useful for patients with an inherited risk of RCC as well as in those who are at risk of tumor recurrence after intervention. Mass screening with the purpose of detecting RCC at its earliest stage is not recommended at the present time, but screening focused on certain risk groups can be advocated. Further research is needed to identify avoidable risks, develop effective chemoprevention and recognize patients at risk.

Carcinoma, Renal Cell↗
PubMed1999

Association of mis-sense substitution in SRD5A2 gene with prostate cancer in African-American and Hispanic men in Los Angeles, USA.

BACKGROUND: Prostate cancer is a very common disease in more-developed countries, but its cause is largely unknown. It is an androgen-dependent cancer, and androgens have been proposed as having a substantial role in predisposition to the disease. Thus, variations in androgen metabolism genes may affect risk of this disease. METHODS: We screened 216 African-American and 172 Hispanic men with prostate cancer, and 261 African-American and 200 Hispanic healthy men (controls), from a large prospective cohort study (the Hawaii-Los Angeles Multiethnic Cohort Study) for a mis-sense substitution in the human prostatic (or type II) steroid 5alpha-reductase (SRD5A2) gene, the product of which controls metabolic activation of testosterone to dihydrotestosterone. This mis-sense substitution results in an alanine residue at codon 49 being replaced with threonine (A49T). We also reconstructed this mutation in the SRD5A2 cDNA, and overexpressed the enzyme in mammalian tissue culture cells. FINDINGS: The A49T aminoacid substitution in the SRD5A2 gene increased the risk of clinically significant disease 7.2-fold in African-American men (95% CI=2.17-27.91; p=0.001) and 3.6-fold in Hispanic men (1.09-12.27; p=0.04). The mutant enzyme had a higher in-vitro Vmax than the normal enzyme (9.9 vs 1.9 nmol min(-1) mg(-1)). INTERPRETATION: The A49T variant of the SRD5A2 gene may be a significant contributor to the incidence of prostate cancer in African-American and Hispanic men in Los Angeles. We estimate that the population attributable risk due to this aminoacid substitution for clinically significant disease is about 8% in both populations. Increased conversion of testosterone to dihydrotestosterone catalysed by this variant steroid 5alpha-reductase enzyme may be the cause of the increased risk.

3-Oxo-5-alpha-Steroid 4-Dehydrogenase↗
PubMed1999

Chronic infection with hepatitis G virus in relation to hepatocellular carcinoma among non-Asians in Los Angeles County, California.

BACKGROUND: The recently identified hepatitis G virus (HGV) is a hepatotropic RNA virus belonging to the Flaviviridae family. The virus causes chronic viremia, and exposure to blood products is a recognized route of transmission in humans. To the authors' knowledge there is scant information regarding the hepatocarcinogenic potential of HGV. The current study examined the association between HGV infection and the risk of hepatocellular carcinoma. METHODS: A population-based, case-control study involving 144 non-Asian patients with hepatocellular carcinoma who were ages 18-74 years at diagnosis and 252 community controls of similar age, gender, and race was conducted in Los Angeles, California. Study subjects were assessed for serologic markers of infections with the hepatitis B virus (hepatitis B surface antigen, antibody to the hepatitis B core antigen, and antibody to the hepatitis B surface antigen), hepatitis C virus (HCV) (anti-HCV and HCV RNA), and HGV (HGV RNA). RESULTS: Twelve of the 144 hepatocellular carcinoma patients (8.3%) and 5 of the 252 control subjects (2.0%) were positive for serum HGV RNA. The presence of HGV RNA in the serum was associated with a statistically significant 5.4-fold risk of hepatocellular carcinoma (95% confidence limit, 1.8, 16.6). The excess risk for hepatocellular carcinoma among HGV-infected individuals was independent of the effects of hepatitis B and hepatitis C infections. CONCLUSIONS: Chronic infection with HGV may play a role in the development of hepatocellular carcinoma. If the observed statistical association is a causal one, then infection with HGV may account for approximately 8% of hepatocellular carcinoma cases occurring in non-Asians in Los Angeles, California.

Adolescent↗
PubMed1999

Urinary 2-hydroxyestrone/16alpha-hydroxyestrone ratio and risk of breast cancer in postmenopausal women.

BACKGROUND: It has been suggested that women who metabolize a larger proportion of their endogenous estrogen via the 16alpha-hydroxylation pathway may be at elevated risk of breast cancer compared with women who metabolize proportionally more estrogen via the 2-hydroxylation pathway. However, the supporting epidemiologic data are scant. Consequently, we compared the ratio of urinary 2-hydroxyestrone (2-OHE1) to 16alphahydroxyestrone (16alpha-OHE1) in postmenopausal women with breast cancer and in healthy control subjects. METHODS: Estrogen metabolites were measured in urine samples obtained from white women who had participated in a previous population-based, breast cancer case-control study at our institution. All P values are from two-sided tests. RESULTS: All of the urinary estrogens measured, with the exception of estriol, were higher in the 66 case patients than in the 76 control subjects. The mean value of urinary 2-OHE1 in case patients was 13.8% (P = .20) higher than that in control subjects, 16alpha-OHE1 was 12.1% (P = .23) higher, estrone was 20.9% higher (P = .14), and 17beta-estradiol was 12.0% higher (P = .36). The ratio of 2-OHE1 to 16alpha-OHE1 was 1.1% higher in the patients (P = .84), contrary to the hypothesis. Compared with women in the lowest third of the values for the ratio of urinary 2-OHE1 to 16alpha-OHE1, women in the highest third were at a nonstatistically significantly increased risk of breast cancer (odds ratio = 1.13; 95% confidence interval = 0.46-2.78), again contrary to the hypothesis. CONCLUSION: This study does not support the hypothesis that the ratio of the two hydroxylated metabolites (2-OHE1/16alpha-OHE1) is an important risk factor for breast cancer.

Aged↗