Biomedical subjects

Thomas E Rohan

Publications and source records attributed to Thomas E Rohan.

At least 19 recordsLinked to original sources

PubMed2026

Height variation independent of known genetic variants and health in later life: a cohort study.

BACKGROUND: Adult-attained height is associated with later-life health, but it reflects both genetic and nongenetic influences. The health implications of height variation not explained by known common height-associated genetic variants remain unclear. OBJECTIVES: This study aimed to examine associations of residual height (height variation independent of known genetic variants) with multiple disease incidence and all-cause mortality in later life. METHODS: In this cohort study of 407,366 adults of European ancestry (aged 40-70 y) in the United Kingdom Biobank (2006-2010), sex- and age-specific genetically predicted height was estimated from 9863 height-associated variants, adjusted for 30 principal components of ancestry. Residual height was calculated as the difference between observed and genetically predicted height. Plasma proteomics (2054 proteins; Olink Explore) were profiled. Deaths and 49 incident diseases were ascertained through national registries. Multivariable Cox models estimated associations of residual height and related proteins with disease incidence and mortality. RESULTS: Higher residual height [mean (standard deviation, SD), 0.0 (4.8)] was associated with more favorable self-reported preadulthood exposures (e.g., later birth years, no maternal smoking around birth, being breastfed as an infant, no adoption experience, and lower childhood adversity scores) and lower hazard ratios (HRs) of 32 out of 49 diseases (median follow-up = ∼12.5 y). Using participants with residual height within ±0.5 SDs from the mean as reference, those with residual height < -2 SDs had higher adjusted HRs of mortality [1.61; 95% confidence interval (CI): 1.50, 1.72], multimorbidity (1.28; 95% CI: 1.12, 1.46), cardiovascular disease (1.45; 95% CI: 1.32, 1.60), psychiatric/neurological disease (1.38; 95% CI: 1.28, 1.48), and other disease categories (e.g., diabetes, digestive, and musculoskeletal diseases). In contrast, higher genetically predicted height was associated with a higher incidence of 19 diseases, including subtypes of cancer, non-atherosclerotic cardiovascular diseases, and musculoskeletal diseases, as well as higher all-cause mortality. We identified 806 plasma proteins related to inflammation, immune response, and autophagy via tumor necrosis factor, Nuclear factor-kappa B, phosphoinositide-3 kinase/protein kinase B, and Janus kinase/signal transducer and activator of transcription signaling pathways, which were associated with residual height and multiple diseases and mortality. CONCLUSIONS: Higher residual height is associated with lower disease incidence and mortality, with associations that are distinct from those for genetically predicted height.

Humans↗

PubMed2003

Human papillomavirus infection and time to progression and regression of cervical intraepithelial neoplasia.

BACKGROUND: Little is known about the duration of precancerous cervical lesions in relation to human papillomavirus (HPV) infection. We estimated rates of progression and regression and sojourn times of cervical squamous intraepithelial lesions (SILs) according to HPV status. METHODS: We used data from a longitudinal study of HPV infection and cervical neoplasia in São Paulo, Brazil. Cervical specimens were taken from 2404 women for Pap cytology and polymerase chain reaction-based HPV testing every 4-6 months over a period of 8 years. We used actuarial and non-actuarial analyses to measure time to and rates of lesion progression and regression according to status and type of HPV infection. RESULTS: During follow-up, 118 low-grade SIL (LSIL), 24 high-grade SIL (HSIL), and 173 atypical squamous cells of undetermined significance (ASCUS) events were detected. Mean time to progression from ASCUS to LSIL or worse and from LSIL to HSIL or worse was shorter in women with oncogenic HPV types than in women with no HPV infection (mean times for ASCUS progression were 67.0 and 88.0 months, respectively, in women with oncogenic HPV and no HPV, difference = 21.0 months, 95% confidence interval [CI] = 11.3 to 30.7 months; mean times for LSIL progression were 73.3 and 83.5 months, respectively, difference = 10.2 months, 95% CI = -0.15 to 20.6 months). Half of the LSILs regressed to normal or ASCUS within 6 months. Mean times for regression from ASCUS to normal, from LSIL to ASCUS or normal, and from HSIL/cervical intraepithelial neoplasia 2 to ASCUS or normal were longer for women with oncogenic HPV types (16.8 months, 95% CI = 7.5 to 26.2 months; 13.8 months, 95% CI = 8.8 to 18.7 months; and 17.1 months, 95% CI = 4.1 to 30.1 months, respectively) than for women with non-oncogenic HPV types (7.7 months, 95% CI = 5.2 to 10.2 months; 7.8 months, 95% CI = 5.3 to 10.2 months; 8.9 months, 95% CI = 3.3 to 14.6 months) or for women with no HPV infection (7.6 months, 95% CI = 6.9 to 8.4 months; 7.6 months, 95% CI = 6.4 to 8.7 months; and 7.0 months, 95% CI = 5.0 to 8.9 months, respectively). CONCLUSION: Precursor lesions of the cervix persist longer and progress more quickly in women with oncogenic HPV infections than in women with non-oncogenic infections or without HPV. Testing cervical lesions for oncogenic HPVs may help identify those that are likely to progress rapidly.

Actuarial Analysis↗

PubMed2003

Misclassification in a matched case-control study with variable matching ratio: application to a study of c-erbB-2 overexpression and breast cancer.

We provide a simple analytic correction for risk factor misclassification in a matched case-control study with variable numbers of controls per case. The method is an extension of existing methodology, and involves estimating the corrected proportions of controls and cases in risk factor categories within each matched set. These estimates are then used to calculate the Mantel-Haenszel odds ratio estimate corrected for misclassification. A simulation-based interval estimate is developed. An example is given from a study of risk factors for progression of benign breast disease to breast cancer, in which the risk factor is a biological marker measured with poor sensitivity.

Breast Neoplasms↗

PubMed2003

Glycemic load, carbohydrate intake, and risk of colorectal cancer in women: a prospective cohort study.

Mounting evidence suggests that high circulating levels of insulin might be associated with increased colorectal cancer risk. The glycemic effects of diets high in refined starch may increase colorectal cancer risk by affecting insulin and/or insulin-like growth factor-I levels. We examined the association between dietary intake and colorectal cancer risk in a cohort of 49 124 women participating in a randomized, controlled trial of screening for breast cancer in Canada. Linkages to Canadian mortality and cancer databases yielded data on mortality and cancer incidence up to December 31, 2000. During an average 16.5 years of follow-up, we observed 616 incident cases of colorectal cancer (436 colon cancers, 180 rectal cancers). Rate ratios for colorectal cancer for the highest versus the lowest quintile level were 1.05 (95% confidence interval [CI] = 0.73 to 1.53; P(trend) =.94) for glycemic load, 1.01 (95% CI = 0.68 to 1.51; P(trend) =.66) for total carbohydrates, and 1.03 (95% CI = 0.73 to 1.44; P(trend) =.71) for total sugar. Our data do not support the hypothesis that diets high in glycemic load, carbohydrates, or sugar increase colorectal cancer risk.

Adult↗

PubMed2003

Viral load as a predictor of the risk of cervical intraepithelial neoplasia.

HPV infections are believed to be a necessary cause of cervical cancer. Viral burden, as a surrogate indicator for persistence, may help predict risk of subsequent SIL. We used results of HPV test and cytology data repeated every 4-6 months in 2,081 women participating in a longitudinal study of the natural history of HPV infection and cervical neoplasia in São Paulo, Brazil. Using the MY09/11 PCR protocol, 473 women were positive for HPV DNA during the first 2 visits. We retested all positive specimens by a quantitative, low-stringency PCR method to measure viral burden in cervical cells. Mean viral loads and 95% CIs were calculated using log-transformed data. RRs and 95% CIs of incident SIL were calculated by proportional hazards models, adjusting for age and HPV oncogenicity. The risk of incident lesions increased with viral load at enrollment. The mean number of viral copies/cell at enrollment was 2.6 for women with no incident lesions and increased (trend p = 0.003) to 15.1 for women developing 3 or more SIL events over 6 years of follow-up. Compared to those with <1 copy per cell in specimens tested during the first 2 visits, RRs for incident SIL increased from 1.9 (95% CI 0.8-4.2) for those with 1-10 copies/cell to 4.5 (95% CI 1.9-10.7) for those with >1,000 copies/cell. The equivalent RR of HSIL for >1,000 copies/cell was 2.6 (95% CI 0.5-13.2). Viral burden appears to have an independent effect on SIL incidence. Measurement of viral load, as a surrogate for HPV persistence, may identify women at risk of developing cervical cancer precursors.

Adolescent↗

PubMed2003

Calibration of the dietary questionnaire for the Canadian Study of Diet, Lifestyle and Health cohort.

OBJECTIVE: For proper interpretation of results from epidemiological studies that use food-frequency questionnaires (FFQs), it is necessary to know the relationship between reported intakes from the FFQ and true usual intake. In this paper, we report a calibration study conducted to investigate the performance of the FFQ used in a cohort study, the Canadian Study of Diet, Lifestyle and Health. METHODS: Over a 1-year period, 151 men and 159 women completed a full set of questionnaires including a self-administered baseline FFQ, three 24-hour diet recalls administered by telephone, and a second FFQ self-administered subsequently. The association between the nutrient estimates derived from the FFQs and the diet recalls was evaluated by calculating deattenuated Pearson's correlation coefficients. RESULTS: FFQs estimated mean daily nutrient intakes higher than the diet recalls. When the log-transformed and energy-adjusted nutrient intakes from the average of three 24-hour recalls were compared against the baseline FFQ, the following deattenuated correlations were obtained in men and women, respectively: total energy 0.44 and 0.32, total fat 0.64 and 0.68, saturated fat 0.68 and 0.70, dietary fibre 0.65 and 0.44, vitamin E 0.32 and 0.37, vitamin C 0.40 and 0.37, beta-carotene 0.34 and 0.29, alcohol 0.74 and 0.67, caffeine 0.81 and 0.76, with a median correlation of 0.49 and 0.53. Correlations between the second FFQ and diet recalls were similar. The correlations between the two FFQs as a test of reliability had a median value 0.64 for men and 0.63 for women for selected nutrients. CONCLUSIONS: The study suggests that the FFQ method gives acceptable levels of nutrients or food component estimates, as assessed by this calibration study against diet recalls, when limited to energy-adjusted and deattenuated values.

Calibration↗

PubMed2003

Intakes of fish and marine fatty acids and the risks of cancers of the breast and prostate and of other hormone-related cancers: a review of the epidemiologic evidence.

Marine fatty acids, particularly the long-chain eicosapentaenoic and docosahexaenoic acids, have been consistently shown to inhibit the proliferation of breast and prostate cancer cell lines in vitro and to reduce the risk and progression of these tumors in animal experiments. However, whether a high consumption of marine fatty acids can reduce the risk of these cancers or other hormone-dependent cancers in human populations is unclear. Focusing primarily on the results of cohort and case-control studies, we reviewed the current epidemiologic literature on the intake of fish and marine fatty acids in relation to the major hormone-dependent cancers. Despite the many epidemiologic studies that have been published, the evidence from those studies remains unclear. Most of the studies did not show an association between fish consumption or marine fatty acid intake and the risk of hormone-related cancers. Future epidemiologic studies will probably benefit from the assessment of specific fatty acids in the diet, including eicosapentaenoic and docosahexaenoic acids, and of the ratio of these to n-6 fatty acids, dietary constituents that have not been examined individually very often.

Animals↗

PubMed2003

Occurrence of cervical infection with multiple human papillomavirus types is associated with age and cytologic abnormalities.

BACKGROUND: Few aspects of the occurrence of infections with multiple HPV types have been described. Since the immunity conferred by vaccines is type-specific, the epidemiology of such coinfections needs to be addressed. GOAL: The goal of the study was to document the prevalence and incidence of infection with multiple HPV types and the distribution of HPV types in coinfections. STUDY DESIGN: In a prospective cohort of 2075 Brazilian women, cervical specimens were collected for cytology and HPV detection. Information on potential risk factors was obtained by interview. RESULTS: The prevalence of HPV coinfections was 3% among cytologically normal women, 10% among women with ASCUS, 23% among those with LSIL, and 7% among those with HSIL. The incidence rate of coinfection declined markedly with age (Ptrend<0.001). Some HPV types co-occurred less frequently than expected, namely, HPV 16 and 18 occurring with other oncogenic HPV types and HPV 6/11. CONCLUSION: We have observed that occurrence of HPV coinfection was dependent both on age and on the presence of cytologic abnormalities. These results may have implications for vaccine development and for public health decisions about vaccination programs.

Adolescent↗

PubMed2002

Cigarette smoking and breast cancer risk: a long latency period?

The association between cigarette smoking and breast cancer risk remains unclear. Few studies have examined cigarette smoking of very long duration as there may not have been a sufficient number of long-term smokers in studies conducted before the 1980s. Therefore, we examined the association between smoking and breast cancer risk using data from participants in a randomized controlled trial of screening for breast cancer involving 89,835 women aged 40-59 years at recruitment and with up to 40 years of smoking duration at that time. Women with breast cancer diagnosed through 31 December 1993 were identified by linkage to the Canadian Cancer Database. Cox proportional hazards models were used to estimate rate ratios (RRs) and 95% confidence intervals (CIs). During an average of 10.6 years of follow-up, we observed 2,552 incident cases of breast cancer. We found a positive association between cigarette smoking and breast cancer risk, driven mainly by women who had smoked for several decades and who, therefore, had commenced smoking many years earlier. Relative to never-smokers, women who had smoked 40 years or more and 20 cigarettes/day or more were at the highest risk (RR = 1.83, 95% CI 1.29-2.61); for women who had commenced smoking 40 years or more before assessment (a measure of smoking latency rather than duration and intensity), the RR was 1.22 (95% CI 0.99-1.59). Our findings suggest that smoking of very long duration and high intensity may be associated with increased risk of breast cancer.

Age Factors↗

PubMed2002

Polymorphisms of the human leukocyte antigen DRB1 and DQB1 genes and the natural history of human papillomavirus infection.

This study investigated, through cohort analysis, whether HLA-DRB1 and -DQB1 variability is related to human papillomavirus (HPV) infection prevalence and persistence. HLA-DRB1 and -DQB1 genes were typed in 620 samples from the Ludwig-McGill cohort. HPV positivity was tested in specimens collected every 4 months during the first year of follow-up. Persistent and long-term infections were defined as at least 2 or 3 consecutive positive results for the same HPV type, respectively. The magnitudes of associations were estimated by unconditional logistic regression analysis adjusted for potential confounders. The DRB1*0301-DQB1*0201 haplotype was associated with a 2-fold reduction in risk for transient and persistent HPV infections. DRB1*1102-DQB1*0301 showed a lower-risk effect only for persistence. DRB1*1601-DQB1*0502 and DRB1*0807-DQB1*0402 were associated with a 7-fold and a 3-fold increase, respectively, in risk for persistence. The results suggest that HLA class II polymorphisms are involved in clearance and maintenance of HPV infection.

Adolescent↗

PubMed2002

Prospective cohort study of cigarette smoking and colorectal cancer risk in women.

Epidemiological studies have consistently found a positive association between cigarette smoking and risk of colorectal adenomas, so the absence of a clear association between smoking and colorectal cancer risk may seem paradoxical. However, if colorectal cancer develops only after an induction period of about 35 years, as has been proposed recently, then studies in which all subjects have fewer than about 35 years between smoking commencement and assessment of outcome would be unlikely to detect this association. Few studies have examined smoking of several decades' duration among women. Therefore, in the cohort study reported here, we used proportional hazards models to estimate hazard ratios relating cigarette smoking to colorectal cancer risk among 89,835 women aged 40-59 years at recruitment into the Canadian National Breast Screening Study, a randomized controlled trial of mammography screening for breast cancer. During an average 10.6 years of follow-up (936,433 person-years), a total of 527 women were diagnosed with incident colorectal cancer (363 colon and 164 rectal). We found that smoking was associated with increased risk of rectal cancer 30 years or more after commencement, and especially with smoking of 40 years' duration or longer (hazard ratio=3.14, 95% CI=1.33-7.42). There was little evidence for altered risk of colon cancer. These results, along with those of other recent studies, support the hypothesis that tobacco smoking is an initiator, rather than a promoter, of rectal cancer. However, the results do not support an association with colon cancer risk, even with smoking of very long duration and high intensity.

Adult↗

PubMed2002

Dietary intake of folic acid and colorectal cancer risk in a cohort of women.

Folate is crucial for normal DNA methylation, synthesis and repair, and deficiency of this nutrient is hypothesized to lead to cancer through disruption of these processes. There is some evidence to suggest that relatively high dietary folate intake might be associated with reduced colorectal cancer risk, especially among individuals with low methionine intake. A case-cohort analysis was undertaken within the cohort of 56,837 women who were enrolled in the Canadian National Breast Screening Study and who completed a self-administered dietary questionnaire. During follow-up to the end of 1993, a total of 389 women were diagnosed with colorectal cancer, identified by linkage to the Canadian Cancer Database. For comparative purposes, a subcohort of 5,681 women was randomly selected from the full dietary cohort at baseline. After exclusions for various reasons, the analyses were based on 295 cases and 5,334 non-cases. Folate intake was inversely associated with colorectal cancer risk (IRR = 0.6, 95% CI = 0.4-1.1, p for trend = 0.25). The inverse association was essentially similar among individuals with low and high methionine intake, and was similar for colon and rectal cancers when those endpoints were analyzed separately. Among individuals with low methionine intake, folate intake did not appear to lower the risk of rectal cancer, a finding that may be due, in part, to the low number of cases in the subgroup analysis. Overall, our data lend some support to the hypothesis that high folate intake is associated with a reduced risk of colorectal cancer.

Body Mass Index↗

PubMed2002

Evidence-based policy recommendations on cancer screening and prevention.

Ideally, practice guidelines for cancer prevention should reflect the available empirical evidence. Although the most persuasive arguments for the efficacy of an intervention come from randomized controlled trials (RCTs), such studies are not always feasible because of ethical or logistical reasons. The advent of evidence-based medicine has underscored the need for consortia of researchers specialized in reviewing the biomedical literature on a systematic basis, ranking studies according to their design, quality, and generalizability of results. This review summarizes the recommendations and policies on screening and prevention of specific types of cancers from North American and international organizations such as: the National Cancer Institute's Physicians's Data Query Program, the US Preventive Services Task Force, the Canadian Task Force on the Preventive Health Care Force, and the Cochrane Collaboration.

Evidence-Based Medicine↗

PubMed2002

Cigarette smoking and the risk of endometrial cancer.

Epidemiological studies have shown that cigarette smoking is associated with a reduced risk of endometrial cancer, in contrast to the increased risks observed with many other non-respiratory-tract cancers, including those of the bladder, pancreas, and cervix uteri. Some studies of endometrial cancer suggest that the inverse association with smoking is limited to certain groups of women, such as those who are postmenopausal or those taking hormone-replacement therapy. The biological mechanisms that might underlie this association remain unclear, although several have been proposed, including an antioestrogenic effect of cigarette smoking on circulating oestrogen concentrations, a reduction in relative bodyweight, and an earlier age at menopause. We have examined the evidence for an association between cigarette smoking and risk of endometrial cancer, including studies related to the proposed biological mechanisms.

Adenocarcinoma↗

PubMed2002

A cohort study of dietary carotenoids and lung cancer risk in women (Canada).

OBJECTIVE: To investigate the association between dietary carotenoid intake and lung cancer risk in women. METHODS: A case-cohort study was undertaken in the Canadian National Breast Screening Study dietary cohort, which consists of 56,837 women who completed a self-administered dietary questionnaire. The cohort was recruited between 1980 and 1985, and during follow-up to the end of 1993 a total of 196 cohort members were diagnosed with incident lung cancer. For analysis, a subcohort consisting of a random sample of 5681 women was selected from the full dietary cohort. After exclusions for various reasons, the analyses were based on 155 cases and 5,361 non-cases. RESULTS: When compared to those in the lowest quartile level of intake, the adjusted incidence rate ratios (95% confidence intervals) for those in the highest quartile levels of alpha-carotene, beta-carotene, beta-cryptoxanthin, lycopene, and lutein intake were 0.90 (0.51-1.58). 1.40 (0.76-2.59), 0.66 (0.33-1.32), 1.04 (0.61-1.76), and 1.26 (0.70-2.24), respectively; none of the associated tests for trend was statistically significant. CONCLUSION: These results suggest that there is no association between dietary carotenoid intake and lung cancer risk. at least for the range of intakes observed here.

Adult↗

PubMed2002

A cohort study of dietary fibre intake and menarche.

OBJECTIVE: To evaluate the influence of dietary fibre on menarche in a cohort of pre-menarcheal girls. DESIGN: Prospective cohort study. SETTING: Ontario, Canada. SUBJECTS: Free-living pre-menarcheal girls (n = 637), 6 to 14 years of age. METHODOLOGY: Information on dietary intake, physical activity and date of menarche was collected at baseline and was updated annually by self-administered questionnaires for three years. Cox proportional hazards models were used to evaluate the association between dietary fibre and menarche, adjusting for age at entry to the study and potential confounders. RESULTS: A higher intake of energy-adjusted dietary fibre was associated with a lower risk of (i.e. a later age at) menarche (relative hazard 0.54, 95% confidence interval (CI) 0.31-0.94 for highest vs. lowest quartile, P for trend = 0.027). At the fibre component level, a higher intake of energy-adjusted cellulose was associated with a lower risk of menarche (relative hazard 0.45, 95% CI 0.26-0.76, P for trend = 0.009). CONCLUSIONS: The findings are consistent with the hypothesis that pre-menarcheal dietary intake can influence menarche.

Adolescent↗

PubMed2002

Dietary carotenoids and risk of breast cancer.

BACKGROUND: Many studies of fruit and vegetable consumption showed inverse associations with breast cancer risk, suggesting the potential importance of carotenoids (and other phytochemicals) contained in these foods. To date, however, only one prospective cohort study has examined dietary carotenoids other than beta-carotene in relation to breast cancer risk. OBJECTIVE: Our aim was to examine the relations between dietary intakes of beta-carotene, alpha-carotene, beta-cryptoxanthin, lycopene, and lutein + zeaxanthin and breast cancer risk in a large cohort study of Canadian women. DESIGN: A case-cohort analysis was undertaken in a cohort of 56 837 women who were enrolled in the Canadian National Breast Screening Study and who completed a self-administered dietary questionnaire. During follow-up to the end of 1993 a total of 1589 women were diagnosed with biopsy-confirmed incident breast cancer. For comparison, a subcohort of 5681 women was randomly selected. After exclusions for various reasons, the analyses were based on 1452 cases and 5239 noncases. RESULTS: We found no clear association between intakes of any of the studied carotenoids and breast cancer risk in the study population as a whole or in subgroups defined by smoking status; relative body weight (assessed by body mass index); intakes of total fat, energy, alcohol, or folic acid; family history of breast cancer; or menopausal status. CONCLUSIONS: Our data do not support any association between dietary intakes of the studied carotenoids and breast cancer risk. However, prospective cohort studies of carotenoids in relation to breast cancer are scarce and further studies are warranted.

Breast Neoplasms↗

PubMed2002

Meat and dairy food consumption and breast cancer: a pooled analysis of cohort studies.

BACKGROUND: More than 20 studies have investigated the relation between meat and dairy food consumption and breast cancer risk with conflicting results. Our objective was to evaluate the risk of breast cancer associated with meat and dairy food consumption and to assess whether non-dietary risk factors modify the relation. METHODS: We combined the primary data from eight prospective cohort studies from North America and Western Europe with at least 200 incident breast cancer cases, assessment of usual food and nutrient intakes, and a validation study of the dietary assessment instrument. The pooled database included 351,041 women, 7379 of whom were diagnosed with invasive breast cancer during up to 15 years of follow-up. RESULTS: We found no significant association between intakes of total meat, red meat, white meat, total dairy fluids, or total dairy solids and breast cancer risk. Categorical analyses suggested a J-shaped association for egg consumption where, compared to women who did not eat eggs, breast cancer risk was slightly decreased among women who consumed < 2 eggs per week but slightly increased among women who consumed > or = 1 egg per day. CONCLUSIONS: We found no significant associations between intake of meat or dairy products and risk of breast cancer. An inconsistent relation between egg consumption and risk of breast cancer merits further investigation.

Animals↗