Biomedical subjects

L A Brinton

Publications and source records attributed to L A Brinton.

At least 19 recordsLinked to original sources

PubMed2006

Established breast cancer risk factors by clinically important tumour characteristics.

Breast cancer is a morphologically and clinically heterogeneous disease; however, it is less clear how risk factors relate to tumour features. We evaluated risk factors by tumour characteristics (histopathologic type, grade, size, and nodal status) in a population-based case-control of 2386 breast cancers and 2502 controls in Poland. Use of a novel extension of the polytomous logistic regression permitted simultaneous modelling of multiple tumour characteristics. Late age at first full-term birth was associated with increased risk of large (> 2 cm) tumours (odds ratios (95% confidence intervals) 1.19 (1.07-1.33) for a 5-year increase in age), but not smaller tumours (P for heterogeneity adjusting for other tumour features (Phet) = 0.007). On the other hand, multiparity was associated with reduced risk for small tumours (0.76 (0.68-0.86) per additional birth; Phet = 0.004). Consideration of all tumour characteristics simultaneously revealed that current or recent use of combined hormone replacement therapy was associated with risk of small (2.29 (1.66-3.15)) and grade 1 (3.36 (2.22-5.08)) tumours (Phet = 0.05 for size and 0.0008 for grade 1 vs 3), rather than specific histopathologic types (Phet = 0.63 for ductal vs lobular). Finally, elevated body mass index was associated with larger tumour size among both pre- and postmenopausal women (Phet = 0.05 and 0.0001, respectively). None of these relationships were explained by hormone receptor status of the tumours. In conclusion, these data support distinctive risk factor relationships by tumour characteristics of prognostic relevance. These findings might be useful in developing targeted prevention efforts.

Breast Neoplasms↗

PubMed2005

Skewed X chromosome inactivation and early-onset breast cancer.

BACKGROUND: Skewed X chromosome inactivation may be more common in women with epithelial ovarian cancer and early-onset breast cancer. We tested this hypothesis in a group of 235 breast cancer patients and 253 controls (mean age 45.8 years) from a larger population based case control study. METHODS: We measured X chromosome inactivation with the AR gene assay in lymphocyte DNA digested with the methylation specific enzyme HpaII. We judged skewness using an adjusted measure (relative to the undigested sample) with a cut point of 75%, and an unadjusted measure where skewed was defined as > 90% of the signal from one allele in the HpaII digested sample. RESULTS: There were no significant differences in any of the skewing measures between cases and controls. Using the adjusted skewing measure among pre-menopausal subjects under the age of 50, 14% of cases versus 11% of controls were skewed, OR = 1.2, 95% CI 0.6 to 2.3; using the unadjusted measure, OR = 0.9, 95% CI 0.4 to 2.0. CONCLUSIONS: While we cannot rule out a subtle difference of approximately twofold or less, we have failed to find a significant difference in the prevalence of skewed X chromosome inactivation in younger women with breast cancer compared to controls.

Adult↗

PubMed2003

Hormonal content and potency of oral contraceptives and breast cancer risk among young women.

Recent use of oral contraceptive pills is associated with a modest risk of breast cancer among very young women. In this US population-based case-control study, we evaluated whether the excess risk associated with recent oral contraceptive use is ubiquitous for all pill types or attributable to specific oral contraceptive preparations. Hormonal content and potency of combination oral contraceptives used for the longest duration within 5 years of interview for breast cancer cases aged 20-44 years (N=1640) were compared with age-matched community controls (N=1492). Women who recently used oral contraceptives containing more than 35 microg of ethinyl oestradiol per pill were at higher risk of breast cancer than users of lower dose preparations when compared to never users (respective relative risks of 1.99 and 1.27, P(trend)<0.01). This relationship was more marked among women <35 years of age, where risks associated with high- and low-dose ethinyl oestradiol use were 3.62 and 1.91 (P(trend)<0.01), respectively. We also found significant trends of increasing breast cancer risk for pills with higher progestin and oestrogen potencies (P(trend)<0.05), which were most pronounced among women aged <35 years of age (P(trend)<0.01). Risk was similar across recently used progestin types. Our findings suggest that newer low-potency/low oestrogen dose oral contraceptives may impart a lower risk of breast cancer than that associated with earlier high-potency/high-dose preparations.

Adult↗

PubMed2001

Association of body size and fat distribution with risk of breast cancer among Chinese women.

Most previous studies addressing the association of body size, weight change and body fat distribution with the risk of breast cancer were conducted in Western societies with a high proportion of overweight people. It remains unclear whether the dose-response relation observed in earlier studies can be extended to women with "normal" weight based on prevailing Western standards. To address this issue, we analyzed data from a population-based case-control study of breast cancer recently completed among Chinese women in urban Shanghai. In-person interviews and anthropometric measurements were completed for 1,459 women newly diagnosed with breast cancer from 25 to 64 years of age and 1,556 controls frequency-matched to cases on age. Unconditional logistic regression was employed to estimate adjusted odds ratios (ORs) and 95% confidence intervals (CI) related to anthropometric variables and self-reported body weight. Currently measured weight, body mass index [BMI: weight (kg)/height(m)(2)] or height was each found to be positively related to risk of postmenopausal breast cancer in a dose-response manner, with ORs (95% CI) being 2.0 (1.4-3.0), 2.0 (1.2-3.2) or 1.7 (1.2-2.5), respectively, for the highest category of weight, BMI or height compared to the lowest category of these variables. These variables were unrelated to premenopausal breast cancer risk. Reported weight at ages >40 years and weight gain after age 20 were more predictive for postmenopausal breast cancer than weight at an earlier age. After adjustment for BMI, waist-to-hip ratio was related to an increased risk of premenopausal [OR = 1.7 (1.3-2.3) for the highest category compared to the lowest category] but not postmenopausal breast cancer. This study suggests that, even in a relatively thin Chinese population, weight gain and height are related to an increased risk of postmenopausal breast cancer, while central fat distribution was associated with premenopausal breast cancer. General weight control may be an effective measurement for breast cancer prevention.

Adipose Tissue↗

PubMed2001

Menopause, hormone replacement therapy and cancer.

OBJECTIVE: To comparatively review available evidence on hormone replacement therapy (HRT) and cancer. METHODS: Qualitative literature review. RESULTS: Most potential favorable and adverse effects on cancer risk of HRT are restricted to current users. On the basis of observational epidemiological data, the RR of breast cancer is moderately elevated in current and recent HRT users, and increases by about 2.3% per year with longer duration of use, but the effect drops after cessation and largely, if not totally, disappears after about 5 years. Unopposed estrogen use is strongly related to endometrial cancer risk, but cyclic combined oestrogen-progestin treatment appears to largely or totally reduce this side effect, if progestin are used for at least 14 days per cycle. However, combined HRT may be associated with higher risk of breast cancer as compared to unopposed estrogens. HRT has been inversely related to colorectal cancer, although the issue of causal relation remains open to discussion. No consistent association was reported for ovarian, liver, other digestive or lung cancer. CONCLUSIONS: Recommendations for prolonged HRT use must be considered on an individual basis, taking into account the presence of other risk factors mainly for breast cancer, such as family history of breast cancer or a personal history of benign breast disease, as well as individual risk for other chronic diseases.

Breast Neoplasms↗

PubMed2001

Comparison of telephone sampling and area sampling: response rates and within-household coverage.

Random digit dialing is used frequently in epidemiologic case-control studies to select population-based controls, even when both cases and controls are interviewed face-to-face. However, concerns persist about the potential biases of random digit dialing, particularly given its generally lower response rates. In an Atlanta, Georgia, case-control study of breast cancer among women aged 20-54 years, all of whom were interviewed face-to-face, two statistically independent control groups were compared: those obtained through random digit dialing (n = 652) and those obtained through area probability sampling (n = 640). The household screening rate was significantly higher for the area sample, by 5.5%. Interview response rates were comparable. The telephone sample estimated a significantly larger percentage (by approximately 7%) of households to have no age-eligible women. Both control groups, appropriately weighted, had characteristics similar to US Census demographic characteristics for Atlanta women, except that respondents in both control groups were more educated and more likely to be married. The authors conclude that households contacted through random digit dialing are somewhat less likely to participate in the household screening process, and if they are cooperative, some households may not disclose that age-eligible women reside therein. Investigators need to develop improved methods for screening and enumerating household members in random digit dialing surveys that target a specific subpopulation, such as women.

Adult↗

PubMed2001

Breast cancer risk in relation to amount of tissue removed during breast reduction operations in Sweden.

BACKGROUND: Women who undergo breast reduction operations have substantially lowered risks of breast cancer, and the reasons remain unclear. The current investigation attempted to assess whether the reduction in breast cancer risk was related directly to the amount of breast tissue removed. METHODS: Medical record retrieval was attempted for 161 breast cancer patients in a Swedish cohort of 31,910 women who had had breast reduction surgery and for 483 women who had not developed breast cancer. Information on amount of breast tissue removed was abstracted along with other factors that influence breast cancer risk. Odds ratios of developing breast cancer were calculated based on amount of breast tissue removed. RESULTS: The amount of tissue removed was a significant predictor of risk, as subjects in the highest quartile of tissue removal had a significantly lower risk than those in the lowest quartile. Considering the total amount of tissue removed (both breasts), subjects with > or = 1600 versus < 800 grams removed had an odds ratio (OR) of 0.24 [95% confidence interval (CI) 0.1-0.5]. This relation persisted after adjustment for other breast cancer risk factors and was apparent within every subgroup examined. CONCLUSIONS: The finding that breast cancer risk was reduced in proportion to the amount of tissue removed should be reassuring to women who are considering breast reduction procedures and to women who are electing to have bilateral total prophylactic mastectomies because of a strong genetic predisposition.

Adolescent↗

PubMed2001

Tumor variants by hormone receptor expression in white patients with node-negative breast cancer from the surveillance, epidemiology, and end results database.

PURPOSE: Hormone receptor expression (presence-positive or absence-negative) may reflect different stages of one disease or different breast cancer types. Determining whether hormone receptor expression represents one or more breast cancer phenotypes would have important paradigmatic and practical implications. METHODS: Breast cancer records were obtained from the National Cancer Institute's Surveillance, Epidemiology, and End Results (SEER) database. The study included 19,541 non-Hispanic white women with node-negative breast cancer. Standard tumor cell characteristics and breast cancer-specific survival were analyzed by independent estrogen receptor (ER+ and ER-), independent progesterone receptor (PR+ and PR-), and joint ERPR expression (ER+PR+, ER+PR-, ER-PR+, and ER-PR-). RESULTS: Age frequency density plots by hormone receptor expression showed two overlapping breast cancer populations with early-onset and/or late-onset etiologies. Independent ER+ and PR+ phenotype were associated with smaller tumor sizes, better grade, and better cancer-specific survival than ER- and PR- breast cancer types. Joint ERPR phenotype exhibited biologic gradients for tumor size, grade, and cancer-specific survival, which ranked from good to worse for ER+PR+ to ER+PR- to ER-PR+ to ER-PR-. CONCLUSION: Variations of standard tumor cell characteristics and breast cancer-specific survival by hormone receptor expression in white patients with node-negative breast cancer suggested two breast cancer phenotypes with overlapping etiologies and distinct clinical features.

Adult↗

PubMed2001

Cancer risk at sites other than the breast following augmentation mammoplasty.

PURPOSE: There has been limited investigation of cancer risk other than breast cancer among patients with breast implants, despite some clinical and laboratory evidence suggesting links with certain cancer sites, including hematopoietic and connective tissue malignancies. METHODS: A retrospective cohort study of 13,488 patients who received cosmetic breast implants at 18 plastic surgery practices in six geographic areas was conducted to assess long-term health effects. After an average of 12 years of follow-up, questionnaires were administered to subjects located and alive (78% of eligible population). Attempts were made to obtain death certificates for deceased subjects and medical verification for all reported cancers. Expected numbers of cancers were derived using general population cancer incidence rates and an internal comparison series of 3936 patients who received other types of plastic surgery at the same practices as the implant patients. RESULTS: A total of 359 malignancies was observed versus 295.95 expected based on general population rates, resulting in a standardized incidence ratio (SIR) of 1.21 [95% confidence interval (CI) 1.1-1.4]. Individual malignancies for which incidence was significantly elevated included cancers of the stomach (SIR = 2.65), cervix (SIR = 3.18), vulva (SIR = 2.51), brain (SIR = 2.16), and leukemia (SIR = 2.19). No excess risks were observed for other hematopoietic malignancies, including multiple myeloma. The internal analyses, however, based on cancer rates derived among the comparison patients, showed no increased cancer risk among the implant patients [relative risk (RR) = 1.00, 95% CI 0.8-1.2], as well as no statistically significant elevations for most individual sites. Cervical cancer continued to be elevated (RR = 1.78), although to a lesser extent than in the external analyses, while the risk for respiratory cancers was higher (RR = 2.40). Non-significant elevations in risk persisted in this analysis for liver cancer (RR = 2.65), brain cancer (RR = 2.83), and leukemia (RR = 1.83). Many of the cancers showing excesses were defined on the basis of death certificates, requiring caution in interpretation. The histologies of the leukemias were quite varied, which makes a biologic relationship appear unlikely. However, respiratory cancers showed some evidence of increasing risk with follow-up time and both respiratory and brain cancers were elevated in the mortality analyses. CONCLUSIONS: Although excesses of cervical and vulvar cancer among implant patients might be attributable to lifestyle factors, reasons for excesses of respiratory and brain cancers were less apparent.

Brain Neoplasms↗

PubMed2001

Associations between smoking and adenocarcinomas and squamous cell carcinomas of the uterine cervix (United States).

OBJECTIVES: Few studies of smoking and cervical carcinoma have addressed the rare cervical adenocarcinomas or used DNA-based tests to control for human papillomavirus (HPV) infection. METHODS: This multicenter case-control study included 124 adenocarcinoma cases, 307 community controls (matched on age, race, and residence to adenocarcinoma cases), and 139 squamous carcinoma cases (matched on age, diagnosis date, clinic, and disease stage to adenocarcinoma cases). Participants completed risk-factor interviews and volunteered cervical samples for PCR-based HPV testing. Polychotomous logistic regression generated adjusted odds ratios (ORs) and 95% confidence intervals (CIs) for both histologic types. RESULTS: Eighteen percent of adenocarcinoma cases, 43% of squamous carcinoma cases, and 22% of controls were current smokers. After control for HPV and other questionnaire data, adenocarcinomas were consistently inversely associated with smoking (e.g. current: OR = 0.6, 95% CI 0.3-1.1; > or = 1 pack per day: OR = 0.7, 95% CI 0.4-1.3), while squamous carcinomas were positively associated with smoking (e.g. current: OR = 1.6, 95% CI 0.9-2.9; > or = 1 pack per day: OR = 1.8, 95% CI 1.0-3.3). Results in analyses restricted to HPV-positive controls were similar. CONCLUSION: Smoking has opposite associations with cervical adenocarcinomas and squamous carcinomas. Although both histologic types are caused by HPV and arise in the cervix, etiologic co-factors for these tumors may differ.

Adenocarcinoma↗

PubMed2001

Effects of mammographic density and benign breast disease on breast cancer risk (United States).

BACKGROUND: Having either a history of benign breast disease, particularly atypical hyperplasia or extensive mammographic breast density, is associated with increased breast cancer risk. Previous studies have described an association between benign breast disease histology and breast density. However, whether these features measure the same risk, or are independent risk factors, has not been addressed. METHODS: This case-control study, nested within the prospective follow-up of the Breast Cancer Detection Demonstration Project, evaluated both benign histologic and mammographic density information from 347 women who later developed breast cancer and 410 age- and race-matched controls without breast cancer. Multivariate logistic regression analyses provided maximum-likelihood estimates of the odds ratios (OR) and 95% confidence intervals (CI) to evaluate the relative risk of breast cancer associated with each exposure. RESULTS: Adjusting for mammographic density, the OR for atypical hyperplasia was 2.1 (95% CI: 1.3-3.6), and adjusting for benign breast histology, the OR for > or = 75% density was 3.8 (95% CI: 2.0-7.2). Women with nonproliferative benign breast disease and > or = 75% density had an OR of 5.8 (95% CI: 1.8-18.6), and women with < 50% density and atypical hyperplasia had an OR of 4.1 (95% CI: 2.1-8.0). CONCLUSIONS: In this study, both benign breast disease histology and the percentage of the breast area with mammographic density were associated with breast cancer risk. However, women with both proliferative benign breast disease and > or = 75% density were not at as high a risk of breast cancer due to the combination of effects (p = 0.002) as women with only one of these factors.

Adult↗

PubMed2001

Patterns and predictors of the breast cancer detection methods in women under 45 years of age (United States).

OBJECTIVES: Few studies have examined methods by which breast cancers are detected, and only one study has been published on predictors of those methods. This study examined patterns and predictors of breast cancer detection methods during 1990-1992 among women age 20-44. METHODS: In-person interview and medical record data were obtained during a population-based case-control study of 1619 women newly diagnosed with breast cancer in three areas of the United States (US). RESULTS: Seventy-one percent of the cancers were identified by self-detection, 9% by routine clinical breast exam (CBE), and 20% by routine mammography. Cancers detected by mammography and CBE, but not those detected by breast self-exam, were much more likely to be early-stage. Detection by mammography increased with age, and a history of mammography use was associated with detection by mammography or CBE. Several commonly studied predictors of screening utilization in the US population were associated with CBE detection, but were less clearly related to or unrelated to mammography detection. CONCLUSION: Findings suggest that, during the 1990s in the US, most breast cancers among women under age 45, including those age 40-44, were self-detected. Few factors other than age and prior screening are verified predictors of method of breast cancer detection.

Adult↗

PubMed2001

Elevated serum homocysteine levels and increased risk of invasive cervical cancer in US women.

OBJECTIVES: To explore the relationship between serum homocysteine, a sensitive biomarker for folate inadequacy and problems in one-carbon metabolism, and invasive cervical cancer. METHODS: A large case-control study was conducted in five US areas with up to two community controls, obtained by random-digit dialing, individually matched to each case. Cervical cancer risk factors were assessed through at-home interview. Blood was drawn at least 6 months after completion of cancer treatment from 51% and 68% of interviewed cases and controls. Serum homocysteine was measured by high-performance liquid chromatography, and exposure to human papillomavirus (HPV) type 16, the most prevalent oncogenic type, was assessed using an enzyme-linked immunosorbent assay. Cases with advanced cancer and/or receiving chemotherapy were excluded, leaving 183 cases and 540 controls. RESULTS: Invasive cervical cancer risk was substantially elevated for women in the upper three homocysteine quartiles (> 6.31 micromol/L); multivariate-adjusted odds ratios ranged from 2.4 to 3.2 (all 95% CIs excluded 1.0). A trend was apparent and significant (p = 0.01). When cases were compared with HPV-16 seropositive controls only, odds ratios were comparable. CONCLUSIONS: Serum homocysteine was strongly and significantly predictive of invasive cervical cancer risk. This association could reflect folate, B12 and/or B6 inadequacy, or genetic polymorphisms affecting one-carbon metabolism.

Adult↗

PubMed2001

Long-term fracture risk among infertile women: a population-based cohort study.

Nulliparity has been linked to bone loss and fractures, but the contribution of infertility is unclear. The purpose of this study was to assess the long-term risk of fractures among infertile women. In a population-based retrospective cohort study, all 658 Olmsted County, Minnesota, women with infertility (failure to conceive after 1 year despite intercourse without contraception) first diagnosed at Mayo Clinic in 1935-1964 were followed for fractures. Risk was assessed by comparing new fractures of each type to the number expected from sex-specific and age-specific fracture rates in the general population (standardized incidence ratios [SIR]). During 18,130 person-years of follow-up, 184 women experienced at least one fracture when 291 would have been expected on the basis of fracture incidence rates in the general population (SIR 0.6, 95% CI 0.5-0.7). There was no increase in proximal femur fractures (SIR 1.0, 95% CI 0.6-1.6) and a statistically significant decrease in the risk of distal forearm fractures (SIR 0.7, 95% CI 0.5-0.97), two of the three sites traditionally associated with osteoporosis. By contrast, there was a significant increase in subsequent vertebral fractures (SIR 1.9, 95% CI 1.4-2.4) that was consistent across divergent causes of infertility and reported menstrual patterns. Although an apparent increase in the risk of vertebral fractures requires further investigation, we saw no indication of an increase in limb fractures, suggesting that infertility does not have long-term adverse skeletal effects like those reported for athletes and dieters with irregular menses.

Adult↗

PubMed2001

Low serum and red blood cell folate are moderately, but nonsignificantly associated with increased risk of invasive cervical cancer in U.S. women.

Previous observational epidemiologic studies of folate and cervical cancer, as well as folate supplementation trials for cervical dysplasia, have produced mixed results. We examined the relationship between serum and RBC folate and incident invasive cervical cancer in a large, multicenter, community-based case-control study. Detailed in-person interviews were conducted, and blood was drawn at least 6 mo after completion of cancer treatment from 51% of cases and 68% of controls who were interviewed. Blood folate was measured with both microbiologic and radiobinding assays. Included in the final analyses were 183 cases and 540 controls. Logistic regression was used to control for all accepted risk factors, including age, sexual behavior, smoking, oral contraceptive use, Papanicolaou smear history and human papillomavirus (HPV)-16 serology. For all four folate measures, the geometric mean in cases was lower than in controls (e.g., 11.6 vs. 13.0 nmol/L, P < 0.01 for the serum radiobinding assay). Folate measures using microbiologic and radiobinding assays were correlated (serum: r = 0.90; RBC: r = 0.77). For serum folate, multivariate-adjusted odds ratios (OR) in the lowest vs. highest quartile were 1.3 [95% confidence interval (CI) = 0.8--2.9] and 1.6 (0.9--2.9), using the microbiologic and radiobinding assays, respectively. For RBC folate, comparable OR were 1.2 (0.6--2.2) and 1.5 (0.8--2.7). Similar risks were obtained when restricting analyses to subjects with a history of HPV infection. Thus, low serum and RBC folate were each moderately, but nonsignificantly, associated with increased invasive cervical cancer risk. These findings support a role for one-carbon metabolism in the etiology of cervical cancer.

Adenocarcinoma↗

PubMed2001

Mortality among augmentation mammoplasty patients.

Much attention has focused on disease risks among women receiving silicone breast implants, but there has been little evaluation of their mortality experience. We undertook a retrospective cohort study of 13,488 women receiving cosmetic implants and 3,936 patients with other types of plastic surgery at 18 plastic surgery practices. After an average of 13 years of follow-up, deficits in overall mortality were found as compared with the general population (U.S. rates) for both implant [255 deaths; standardized mortality ratio (SMR) = 0.69, 95% confidence interval (CI) = 0.6-0.8] and comparison subjects (125 deaths; SMR = 0.58, 95% CI = 0.5-0.7). These findings indicate that patients seeking plastic surgery are in general healthier than their peers. Implant patients, however, experienced excess risks of death compared with the general population for brain cancer (SMR = 2.45) and suicide (SMR = 1.54). Internal analyses showed a higher overall mortality among the implant than among the comparison patients (relative risk = 1.27, 95% CI = 1.0-1.6). This overall excess reflected increases for respiratory tract (SMR = 3.03) and brain (SMR = 2.25) cancers and for suicide (SMR = 4.24).

Adult↗

PubMed2001

Evaluation of self-collected cervicovaginal cell samples for human papillomavirus testing by polymerase chain reaction.

As human papillomavirus (HPV) becomes accepted as the central cause of cervical cancer, longitudinal studies are shifting focus away from causality to a more detailed investigation of the natural history of HPV infections. These studies commonly require repeated samples for HPV testing over several years, usually collected during a pelvic exam, which is inconvenient to the participants and costly to the study. To alleviate the inconvenience and cost of repeated clinic visits, it has been proposed that women collect cervicovaginal cells themselves, hopefully increasing participation in the natural history studies. We evaluated the technical feasibility of self-collection of cervicovaginal cells using a Dacron swab for HPV DNA detection. We compared the self-collected swab sample and two clinician-administered swab samples (one from the endocervix and another from the ectocervix) from a total of 268 women participating in a case-control study of adenocarcinoma and squamous cell carcinomas of the uterine cervix (111 cases and 157 controls). HPV DNA was detected and genotyped using an L1 consensus PCR assay. The overall agreement between the clinician- and self-collected swabs was excellent [88.1%; kappa = 0.73 (95% confidence interval (CI), 0.61-0.85)]. The correlation was highest between the two clinician-administered swabs [kappa = 0.81 (95% CI, 0.69-0.93)] but was still excellent when comparing either clinician-administered swab to the self-administered sample [kappa = 0.75 (95% CI, 0.63-0.87) and 0.67 (95% CI, 0.55-0.79) for ectocervix and endocervix, respectively]. The type-specific agreement between samples was higher for high-risk, or cancer-associated, HPV genotypes than for low risk, noncancer-associated HPV genotypes when comparing the self-administered swab sample to the clinician-administered swab sample (kappa = 0.78 for high-risk versus 0.66 for low-risk HPV infections, t = -1.45, P = 0.15). The decrease in agreement for low risk types was largely attributable to an increased detection of these types in the self-administered sample (McNemar's chi2 = 6.25, P = 0.01 for clinician- versus self-administered swab comparisons). The agreement did not vary significantly by age, menopausal status, case status, or clinic center. We have demonstrated that a self-collected Dacron swab sample of cervicovaginal cells is a technically feasible alternative to clinician-administered cervical cell collection in natural history studies of HPV and cervical cancer.

Adolescent↗

PubMed2001

Collection of genomic DNA from adults in epidemiological studies by buccal cytobrush and mouthwash.

Blood samples are an excellent source of large amounts of genomic DNA. However, alternative sources are often needed in epidemiological studies because of difficulties in obtaining blood samples. This report evaluates the buccal cytobrush and alcohol-containing mouthwash protocols for collecting DNA by mail. Several DNA extraction techniques are also evaluated. The study was conducted in two phases. In phase 1, we compared cytobrush and mouthwash samples collected by mail in two different epidemiological studies: (a) cytobrush samples (n = 120) from a United States case-control study of breast cancer; and (b) mouthwash samples (n = 40) from a prospective cohort of male United States farmers. Findings from phase 1 were confirmed in phase 2, where we randomized cytobrush (n = 28) and mouthwash (n = 25) samples among participants in the breast cancer study to directly compare both collection methods. The median human DNA yield determined by hybridization with a human DNA probe from phenol-chloroform extracts was 1.0 and 1.6 microg/2 brushes for phases 1 and 2, respectively, and 27.5 and 16.6 microg/mouthwash sample for phases 1 and 2, respectively. Most (94-100%) mouthwash extracts contained high molecular weight DNA (>23 kb), in contrast to 55-61% of the brush extracts. PCR success rates for amplification of beta-globin gene fragments (268, 536, and 989 bp) were similar for cytobrush and mouthwash phenol-chloroform extracts (range, 94.4-100%). Also, we obtained high success rates in determining the number of CAG repeats in the androgen receptor gene, characterizing tetranucleotide microsatellites in six gene loci, and screening for mutations in the BRCA1/2 genes in a subset of phenol-chloroform DNA extracts. Relative to DNA extracted by phenol-chloroform from cytobrush samples, DNA extracted by NaOH had lower molecular weight, decreased PCR success rates for most assays performed, and unreliably high spectrophotometer readings for DNA yields. In conclusion, although DNA isolated from either mouthwash or cytobrush samples collected by mail from adults is adequate for a wide range of PCR-based assays, a single mouthwash sample provides substantially larger amounts and higher molecular weight DNA than two cytobrush samples.

Adult↗