Re: Recent trends in U.S. breast cancer incidence, survival, and mortality rates.
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Adult↗
Biomedical subjects
M C Pike
Publications and source records attributed to M C Pike.
Genetic variation of 3 beta-hydroxysteroid dehydrogenase type II in three racial/ethnic groups: implications for prostate cancer risk.
BACKGROUND: Elevated prostatic dihydrotestosterone (DHT) has been suggested to increase the risk of prostate cancer. The HSD3B2 gene encodes the type II 3 beta-hydroxysteroid dehydrogenase: one of two enzymes that initiate the inactivation of DHT. Thus, the HSD3B2 gene is a candidate gene for predisposition to prostate cancer. METHODS: We have determine the distribution of a complex dinucleotide repeat in the HSD3B2 gene in high-risk African-Americans, intermediate-risk Euro-Americans, and low-risk Asians. Genomic DNA from 312 individuals was amplified by polymerase chain reaction (PCR) and analyzed by electrophoresis on denaturing polyacrylamide gels. RESULTS: We have found that certain alleles are either unique to or much more common in either African-Americans, Asians, or Euro-Americans. Our data also substantially expand the number of alleles reported for the complex dinucleotide repeat polymorphism in the HSD3B2 gene. CONCLUSIONS: Our report demonstrates substantial genetic variation in the HSD3B2 gene. We hypothesize that allelic variants of the HSD3B2 gene may play a role in predisposition to prostate cancer, and in explaining the substantial racial/ethnic variation in risk.
3-Hydroxysteroid Dehydrogenases↗
Does oral contraceptive use increase the risk of breast cancer in women with BRCA1/BRCA2 mutations more than in other women?
We conducted a study to determine whether the risk of breast cancer associated with oral contraceptive (OC) use is higher in women with BRCA1/BRCA2 mutations than in other women by examining whether breast cancer patients with these mutations were more likely than breast cancer patients without mutations in BRCA1/BRCA2 to have used OCs. We tested for BRCA1 185delAG and 5382insC and BRCA2 6174delT mutations in a population-based sample of 50 young Ashkenazi Jewish breast cancer patients. Nine patients (18%) had a BRCA1 mutation, and five patients (10%) had a BRCA2 mutation. Long-term OC use (>48 months) before a first full-term pregnancy was associated with an elevated risk of being classified as a mutBRCA carrier (odds ratio, 7.8; trend, P = 0.004). The results suggest that OC use may increase the risk of breast cancer more in mutBRCA carriers than in noncarriers; however, they must be interpreted with caution given the small sample size.
Adult↗
Estrogen-progestin replacement therapy and endometrial cancer.
BACKGROUND: It has been known for more than 20 years that estrogen replacement therapy substantially increases a woman's risk of developing endometrial cancer. To reduce this increased risk, progestins have been added to estrogen replacement therapy for between 5 and 15 days (usually 7 or 10 days) per "month" in a sequential fashion (sequential estrogen-progestin replacement therapy) or with each dose of estrogen replacement therapy (continuous combined replacement therapy). At the present time, however, little is known about the effects of varying the number of days that progestin is used in sequential estrogen-progestin replacement therapy. PURPOSE: We sought to determine the effects of sequential estrogen-progestin replacement therapy and continuous combined replacement therapy on a woman's risk of developing endometrial cancer. METHODS: A population-based, case-control study of 833 case subjects and 791 control subjects was conducted. Women were postmenopausal, white, and aged 50-74 years when first diagnosed with invasive endometrial cancer or were aged 50-74 years at the matching date for control subjects. All subjects were interviewed in person with the aid of a month-by-month calendar. Relative risks were estimated by odds ratios (ORs); ORs were adjusted simultaneously for the different forms of hormone replacement therapy and for the known endometrial cancer risk factors. RESULTS: The adjusted OR was 2.17 (95% confidence interval [CI] = 1.91-2.47) per 5 years of estrogen replacement therapy use (based on 422 users among the case subjects and 262 users among the control subjects). For women who received sequential estrogen-progestin replacement therapy with the progestin given for less than 10 days (effectively 7 days) per month, the adjusted OR was only slightly reduced to 1.87 (95% CI = 1.32-2.65) per 5 years of use (74 case subjects and 47 control subjects). However, when progestin was given for 10 or more days (effectively 10 days), there was essentially no increased risk (adjusted OR = 1.07 per 5 years of use; 95% CI = 0.82-1.41) (79 case subjects and 88 control subjects). Continuous combined replacement therapy was also associated with essentially no increased risk (adjusted OR = 1.07 per 5 years of use; 95% CI = 0.80-1.43) (94 case subjects and 81 control subjects). CONCLUSIONS: The progestin in sequential estrogen-progestin replacement therapy needs to be given for at least 10 days to block effectively any increased risk of endometrial cancer. Continuous combined estrogen-progestin therapy is similarly effective. Neither regimen reduces a woman's underlying risk of endometrial cancer. The sharp distinction between the effects of less than 10 days (effectively 7 days) and 10 or more days (effectively 10 days) of progestin use in sequential estrogen-progestin replacement therapy suggests that the extent of endometrial sloughing may play a critical role in determining endometrial cancer risk.
Aged↗
Risk of testicular cancer in cohort of boys with cryptorchidism.
OBJECTIVE: To determine the risk of testicular cancer in relation to undescended testis and its treatment based on recorded details of the maldescent, treatment, and biopsy from case notes. DESIGN: Cohort study. SETTING: Hospital for Sick Children, Great Ormond Street, London. SUBJECTS: 1075 boys with cryptorchidism treated by orchidopexy or hormones at the hospital during 1951-64. MAIN OUTCOME MEASURES: Relative risk of testicular cancer in the cohort compared with men in the general population. RESULTS: 12 testicular cancers occurred in 11 of the patients during follow up to mid-1990 (relative risk of cancer in males with cryptorchidism = 7.5 (95% confidence interval 3.9 to 12.8)). The relative risk fell significantly beyond 15 years after orchidopexy but did not decrease with younger age at orchidopexy. Risk was significantly raised in testes that had had biopsy samples removed during orchidopexy (relative risk = 66.7 (23.9 to 143.3) compared with a testis in a man in the general population) and was significantly greater in these testes than in undescended testes that had not had biopsy samples taken at orchidopexy (6.7 (2.7 to 13.5)). No reasons for biopsy or distinguishing clinical aspects of the testes that had had biopsy samples taken and later developed malignancies were evident in the case notes. No histological abnormalities were evident at initial biopsy except in one testis that had features of dysgenesis. CONCLUSIONS: Biopsy seems to be a stronger risk factor for testicular cancer than any factor previously identified. The trauma of open biopsy may contribute substantially to risk of malignancy or the testes may have been selected for biopsy on the basis of clinical factors predictive of malignancy but not mentioned in the case notes.
Adolescent↗
A prevalent missense substitution that modulates activity of prostatic steroid 5alpha-reductase.
Prostate cancer is the most common serious cancer diagnosed in men in the United States. This disease is also characterized by a striking racial/ethnic variation in incidence: highest in African-Americans, intermediate in Caucasians, slightly lower in Latinos, and lowest in Asians. Ample biochemical and epidemiological evidence suggests a role for androgens, particularly testosterone and dihydrotestosterone, in prostate cancer etiology. We have analyzed a candidate gene for prostate cancer, SRD5A2, encoding prostatic steroid 5alpha-reductase type II, which converts testosterone into the more bioactive dihydrotestosterone, for mutations. We report here one amino acid substitution, V89L, which replaces valine at codon 89 with leucine. This substitution is a "germline" (constitutional) DNA polymorphism, and it is common, panethnic, and reduces in vivo steroid 5alpha-reductase activity. This substitution is particularly common among Asians and may explain the low risk for prostate cancer in this population.
3-Oxo-5-alpha-Steroid 4-Dehydrogenase↗
Evaluation of an expert system on lymph node pathology.
BACKGROUND: Pathfinder is an Expert System that assists pathologists in making accurate diagnoses in the domain of lymph-node pathology. Pathfinder provides a differential diagnosis based on the initial histological feature(s) observed by the pathologist, and suggests to the user additional histological features for observation that are likely to narrow the differential diagnosis. PURPOSE: To evaluate the diagnostic accuracy of pathologists with and without the Pathfinder. METHODS: Thirty H&E stained slides from 30 lymph node biopsy specimens on which a Consensus diagnosis was made by two experts were reviewed by 19 pathologists to evaluate Pathfinder. After a period of training, 10 pathologists using Pathfinder (Interactive Computer Method) and 9 pathologists using the Routine Method (diagnosis without computer) determined a differential diagnosis for 15 slides (Test 1). Pathologists were then crossed over, trained, and evaluated the remaining 15 slides (Test 2). For each test, the proportion of "correct" diagnoses was compared between methods. In addition, the information integration attributes (making logical diagnosis given a set of specific histologic features) of Pathfinder and pathologists were compared. Finally, feature identification and quantification skills of pathologists were determined and correlated with the percent correct diagnosis. RESULTS: The diagnostic accuracy using Pathfinder was greater than that using the Routine Method (40% v 32%, P = .02). Diagnostic accuracy for the group of pathologists who made diagnosis using the Routine Method in Test 1 increased when they made diagnosis using Pathfinder in Test 2 (27% to 44%, P < .0001). The proportion of correct diagnosis for the group of pathologists who used Pathfinder in Test 1 remained virtually unchanged when they gave up Pathfinder in Test 2 (35% to 37%). The percentage of incompatible feature identification ("atypical proliferation" diagnosis) was significantly lower after using Pathfinder (P < .0001). In addition, information integration attributes of Pathfinder were significantly superior than that of the pathologists (P < .0001). CONCLUSIONS: Pathfinder is a valuable tool that assists pathologists in making accurate diagnosis because it has superior attributes than pathologists to integrate information and to screen for observations incompatible with any specific disease.
Biopsy↗
A pilot study of urinary estrogen metabolites (16alpha-OHE1 and 2-OHE1) in postmenopausal women with and without breast cancer.
The two main pathways for metabolizing estrogen are via 16alpha-hydroxylation and 2-hydroxylation. The 16alpha-hydroxy metabolites are biologically active; the 2-hydroxy metabolites are not. It is suggested that women who metabolize a larger proportion of their endogenous estrogen via the 16alpha-hydroxy pathway may be at significantly elevated risk of breast cancer compared with women who metabolize proportionally more estrogen via the 2-hydroxy pathway. In particular, it is suggested that the ratio of urinary 2-hydroxyestrone (2-OHE1) to 16alpha-hydroxyestrone (16alpha-OHE1) is an index of reduced breast cancer risk. This pilot study compared this ratio in postmenopausal women diagnosed with breast cancer to those of healthy controls. Urinary concentrations of estrone (E1), 17beta-estradiol (E2) and estriol (E3) were also quantified. White women who were subjects in a previous breast cancer case-control study at our institution were eligible for inclusion. All participants provided a sample of their first morning urine. The results from the first 25 cases and 23 controls are presented here. The ratio of 2-OHE1 to 16alpha-OHE1 was 12% lower in the cases (p=0.58). However, urinary E1 was 30% higher (p=0.10), E2 was 58% higher (p=0.07), E3 was 15% higher (p=0.48), and the sum of E1, E2, and E3 was 22% higher (p=0.16) in the cases. These preliminary results do not support the hypothesis that the ratio of the two hydroxylation metabolites (2-OHE1/16alpha-OHE1) is an important risk factor for breast cancer or that it is a better predictor of breast cancer risk than levels of E1, E2 and E3 measured in urine.
Breast Neoplasms↗
Relative weight, weight change, height, and breast cancer risk in Asian-American women.
BACKGROUND: Breast cancer incidence rates have historically been four to seven times higher in the United States than in China or Japan, although the reasons remain elusive. When Chinese, Japanese, or Filipino women migrate to the United States, their breast cancer risk rises over several generations and reaches that for white women in the United States, indicating that modifiable exposures are involved. In a previous report on this case-control study of breast cancer in Asian-American women, designed to take advantage of their diversity in risk and lifestyle, we demonstrated a sixfold gradient in risk by migration history, comparable to the international differences in breast cancer incidence rates. PURPOSE: In this analysis, we have examined the roles of adult height, adiposity, and weight change in breast cancer etiology. METHODS: A population-based, case-control study of breast cancer was conducted among women of Chinese, Japanese, and Filipino ethnicities, aged 20-55 years, living in San Francisco-Oakland (CA), Los Angeles (CA), and Oahu (HI) during the period from April 1, 1983, through June 30, 1987. We successfully interviewed 597 (70%) of 852 eligible case subjects and 966 (75%) of 1287 eligible control subjects from August 1985 through February 1989. Subjects were asked about current height, usual adult weight, and usual weight in each decade of life, excluding the most recent 3 years and any periods of pregnancy. RESULTS: Height, recent adiposity (weight in the current decade of life/height 1.5), and recent weight change (between the current and preceding decades of life) were strong predictors of breast cancer risk after adjustment was made for accepted breast cancer risk factors. Risk doubled (relative risk [RR] = 2.01; 95% confidence interval [CI] = 1.16-3.49) over the 7-inch (17.8-cm) range in height (two-sided P for trend = .003), with comparable effects in both premenopausal and postmenopausal women. Except for reduced risk in the heavy, younger women (weight/height 1.5 > 29 kg/m 1.5 and < 40 years old), risk was positively associated with usual adult adiposity. Trends in risk became more striking as adiposity in each succeeding decade of adult life was considered. Women in their 50s and in the top quintile for their age group had twice the breast cancer risk (RR = 2.13; 95% CI = 1.17-3.87) of women in the bottom quintile (two-sided P for trend = .004). Women in their 50s, above the median adiposity for their age group, and with a recent gain of more than 10 pounds had three times the risk (RR = 3.01; 95% CI = 1.45-6.25) of women below the median adiposity and with no recent weight change. Recent weight loss was consistently associated with reduced risk (RRs of approximately 0.7) relative to no recent weight change. CONCLUSIONS: Adult adiposity, weight change, and height are critical determinants of breast cancer risk. Increased adiposity and weight gain in the decade preceding diagnosis are especially influential, suggesting that excess weight may function as a late stage promoter. IMPLICATIONS: Weight maintenance and/or reduction as an adult, possibly accompanied by specific changes in diet and physical activity, may have a significant and rapid impact on breast cancer risk.
Adult↗
N-terminus urea-substituted chemotactic peptides: new potent agonists and antagonists toward the neutrophil fMLF receptor.
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Amino Acid Sequence↗
Selective inhibition of N-formylpeptide-induced neutrophil activation by carbamate-modified peptide analogues.
Stimulation of the leukocyte N-formylpeptide receptor (FPR) induces chemotaxis, cell adhesion, free radical release, and degranulation, responses associated with infection and inflammation. Under conditions where continuous activation of the receptor prevails, neutrophil-dependent tissue damage ensues. Antagonists of the FPR have potential for use as diagnostic and therapeutic agents. Hence, we have synthesized and evaluated a series of amino-terminal carbamate analogues of the peptide Met-Leu-Phe (MLF) in order to determine the structural requirements for imparting agonist or antagonist activity at the human neutrophil FPR. Peptides were evaluated in three in vitro assays: receptor binding, superoxide anion release, and cell adhesion. Unbranched carbamates (methoxycarbonyl, ethoxycarbonyl, and n-butyloxycarbonyl) resulted in agonist activity, whereas branched carbamates (iso-butyloxycarbonyl, tert-butyloxycarbonyl, and benzyloxycarbonyl) were antagonists. The peptide antagonists were more potent inhibitors of superoxide anion release than cell adhesion by 4-7-fold. When iso-butyloxycarbonyl-MLF (i-Boc-MLF) was further modified at the carboxy terminus with Lys, antagonist potency was retained but without functional selectivity. Further C-terminal modification with the radionuclide linker diethylenetriaminepentaacetic acid did not alter the potency of i-Boc-MLFK. These results indicate that the switch from agonist to antagonist activity can be achieved by modifying the overall size and shape of the amino-terminal group; that modifications at both the amino and carboxy termini can alter the functional selectivity of the peptide; and that modifications can be tolerated at the carboxy terminus to allow for development of an antagonist for diagnostic applications.
Adult↗
Can mammographic densities predict effects of tamoxifen on the breast?
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Adult↗
Sexual, reproductive, and other risk factors for adenocarcinoma of the cervix: results from a population-based case-control study (California, United States)
The incidence of adenocarcinoma of the cervix increased steadily in young women in the United States between the early 1970s and the mid-1980s. Despite this increase, little is known about the etiology of this cancer, although a role for risk factors for both squamous cell carcinoma of the cervix and endometrial adenocarcinoma has been suggested. Incident cases of adenocarcinoma of the cervix diagnosed in women born after 1935 (ages 42 to 56 at diagnosis) were identified from the Los Angeles (California) County Cancer Surveillance Program (LACCSP). Data from personal interviews with 195 cases and 386 controls (matched on age, race, and neighborhood) were analyzed. Compared with women in the highest categories of education and income, women in the lowest categories had a 2.5 and 3.1-fold elevated risk of adenocarcinoma of the cervix. Number of sexual partners, especially before age 20, was strongly predictive of risk (odds ratio = 5.6, 95 percent confidence interval = 1.4-22.0 for 10 or more compared with no partners before age 20). Smoking was not associated significantly with risk. Weight gain and long-term use of oral contraceptives increased risk, while long-term diaphragm use was protective. This study suggests that both sexual and hormonal factors are important etiologic factors for adenocarcinoma of the cervix.
Adenocarcinoma↗
Progesterone concentrations--physiologic or pharmacologic?
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Administration, Topical↗
Menstrual and reproductive factors and risk of breast cancer in Asian-Americans.
We conducted a population-based case-control study of breast cancer among Chinese-, Japanese- and Filipino-American women in Los Angeles County Metropolitan Statistical Area (MSA), San Francisco-Oakland MSA and Oahu, Hawaii. One objective of the study was to quantify breast cancer risks in relation to menstrual and reproductive histories in migrant and US-born Asian-Americans and to establish whether the gradient of risk in Asian-Americans can be explained by these factors. Using a common study design and questionnaire in the three study areas, we successfully conducted in-person interviews with 597 Asian-American women diagnosed with incident, primary breast cancer during the period 1983-87 (70% of those eligible) and 966 population-based controls (75% of those eligible). Controls were matched to cases on age, ethnicity and area of residence. In the present analysis, which included 492 cases and 768 controls, we observed a statistically non-significant 4% reduction in risk of breast cancer with each year delay in onset of menstruation. Independent of age at menarche risk of breast cancer was lower (odds ratio; OR=0.77) among women with menstrual cycles greater than 29 days. Parous Asian-American women showed a significantly lower risk of breast cancer then nulliparous women (OR=0.54). An increasing number of livebirths and a decreasing age at first livebirth were both associated with a lower risk of breast cancer, although the effect of number of livebirths was no longer significant after adjustment for age at first livebirth. Women with a pregnancy (spontaneous or induced abortions) but no livebirth had a statistically non-significant increased risk (OR=1.84), but there was no evidence that one type of abortion was particularly harmful. A positive history of breastfeeding was associated with non-significantly lower risk of breast cancer (OR=.78). There are several notable differences in the menstrual and reproductive factors between Asian-Americans in this study and published data on US whites. US-born Asian Americans had an average age at menarche of 12.12 years-no older than has been found in comparable studies of US whites, but 1.4 years earlier than Asian women who migrated to the US. Asian-American women, particularly those born in the US and those who migrated before age 36, also had a later age at first birth and fewer livebirths than US whites. A slightly higher proportion of Asian-American women breastfed, compared with US whites. The duration of breastfeeding was similar in US-born Asians and US whites, but was longer in Asian migrants, especially those who migrated at a later age. Menstrual and reproductive factors in Asian-American women are consistent with their breast cancer rates being at least as high as in US whites, and they are. However, the effects of these menstrual and reproductive factors were small and the ORs for migration variables changed only slightly after adjustment for these menstrual and reproductive factors. These results suggest that the lower rates of breast cancer in Asians must be largely as a result of other environmental/lifestyle factors.
Adult↗
A case-control study of cryptorchidism and maternal hormone concentrations in early pregnancy.
Serum samples taken between 6 and 20 weeks of gestation were obtained from 28 mothers who gave birth to cryptorchid sons (cases) and from 108 control mothers. In comparison with controls the cases had 10% higher geometric mean oestradiol (95% CI -13% to +39%: P=0.42) and 10% lower geometric mean testosterone (95% CI -27% to +10%: P=0.30). Among the samples collected between 6 and 14 weeks of gestation geometric mean concentrations of oestradiol and testosterone were 5% lower (95% CI -32% to +31%: P=0.74) and 25% lower (95% CI -45% to +1%: P=0.06) respectively in cases than in controls. Among the samples collected between 15 and 20 weeks of gestation geometric mean concentrations of oestradiol and testosterone were 29% higher (95% CI -8% to +79%: P=0.14) and 21% higher (95% CI -8% to +60%: P=0.18) respectively in cases than in controls. The results do not support the hypothesis that cryptorchidism may be caused by high concentrations of oestradiol in the maternal blood during the first phase of testicular descent, but suggest that the possible association of cryptorchidism with low maternal testosterone during early gestation should be further investigated.
Adult↗
A prospective study of urinary oestrogen excretion and breast cancer risk.
To test the hypothesis that high levels of endogenous oestrogens increase the risk for developing breast cancer, concentrations of oestrone, oestradiol and oestriol were measured in 24 h urine samples from 1000 women participants in a prospective study of breast cancer on the island of Guernsey. Sixty-nine subjects were diagnosed with breast cancer subsequent to urine collection. Among women who were premenopausal at the time of urine collection, cases excreted less oestrogen than controls; the odds ratios (95% CI) for breast cancer in the middle and upper thirds of the distribution of oestrogen excretion, in comparison with the lower third (reference group, assigned odds ratio = 1.0), were 0.5(0.2-1.2) and 0.4(0.2-1.1) respectively for oestrone, 0.8(0.4-1.8 and 0.4(0.2-1.1) for oestradiol, 0.7(0.3-1.6) and 0.7(0.3-1.6) for oestriol and 0.9(0.4-2.0) and 0.5(0.2-1.3) for total oestrogens. Among women who were post-menopausal at the time of urine collection, the trend was in the opposite direction, with an increase in risk associated with increased oestrogen excretion; the odds ratios were 0.9(0.3-2.2) and 1.1(0.5-2.8) for oestrone, 0.8(0.3-2.3) and 1.9(0.8-4.6) for oestradiol, 1.5(0.6-3.9) and 1.8(0.7-4.6) for oestriol and 0.9(0.4-2.6) and 1.9(0.7-4.7) for total oestrogens. The trends of increasing risk with increasing oestrogen excretion among post-menopausal women were statistically significant for oestradiol (P = 0.022) and for total oestrogens (P = 0.016). We conclude that high levels of endogenous oestrogens in post-menopausal women are associated with increased breast cancer risk, but that the relationship of oestrogens in premenopausal women with risk is unclear.
Adult↗
Cigarette smoking and urinary oestrogen excretion in premenopausal and post-menopausal women.
Cigarette smoking is associated with a reduction in the risk for endometrial cancer in post-menopausal women and it has been suggested that this is because smoking has an anti-oestrogenic effect. To investigate this, concentrations of oestrone, oestradiol and oestriol were measured in 24 h urine samples from 167 premenopausal women (53 smokers, 114 non-smokers) and 200 post-menopausal women (54 smokers, 146 non-smokers). Among premenopausal women there were no significant differences in oestrogen excretion between smokers and non-smokers. Among post-menopausal women, geometric mean excretion rates for oestrone and oestradiol did not differ significantly between groups, but oestriol excretion was 19% lower (95% confidence interval -34% to -1%) in smokers than in non-smokers. This may partly explain the reduced risk for endometrial cancer among post-menopausal smokers.
Adult↗