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Biomedical subjects

David J Hunter

Publications and source records attributed to David J Hunter.

At least 109 records · Page 6Linked to original sources

The progesterone receptor Val660-->Leu polymorphism and breast cancer risk.

BACKGROUND: Recent evidence suggests a role for progesterone in breast cancer development and tumorigenesis. Progesterone exerts its effect on target cells by interacting with its receptor; thus, genetic variations, which might cause alterations in the biological function in the progesterone receptor (PGR), can potentially contribute to an individual's susceptibility to breast cancer. It has been reported that the PROGINS allele, which is in complete linkage disequilibrium with a missense substitution in exon 4 (G/T, valine-->leucine, at codon 660), is associated with a decreased risk for breast cancer. METHODS: Using a nested case-control study design within the Nurses' Health Study cohort, we genotyped 1252 cases and 1660 matched controls with the use of the Taqman assay. RESULTS: We did not observe any association of breast cancer risk with carrying the G/T (Val660-->Leu) polymorphism (odds ratio 1.10, 95% confidence interval 0.93-1.30). In addition, we did not observe an interaction between this allele and menopausal status and family history of breast cancer as reported previously. CONCLUSION: Overall, our study does not support an association between the Val660-->Leu PROGINS polymorphism and breast cancer risk.

Breast Neoplasms↗

Dairy foods, calcium, and colorectal cancer: a pooled analysis of 10 cohort studies.

BACKGROUND: Studies in animals have suggested that calcium may reduce the risk of colorectal cancer. However, results from epidemiologic studies of intake of calcium or dairy foods and colorectal cancer risk have been inconclusive. METHODS: We pooled the primary data from 10 cohort studies in five countries that assessed usual dietary intake by using a validated food frequency questionnaire at baseline. For most studies, follow-up was extended beyond that in the original publication. The studies included 534 536 individuals, among whom 4992 incident cases of colorectal cancer were diagnosed between 6 and 16 years of follow-up. Pooled multivariable relative risks for categories of milk intake and quintiles of calcium intake and 95% confidence intervals (CIs) were calculated. All statistical tests were two-sided. RESULTS: Milk intake was related to a reduced risk of colorectal cancer. Compared with the lowest category of intake (<70 g/day), relative risks of colorectal cancer for increasing categories (70-174, 175-249, and > or =250 g/day) of milk intake were 0.94 (95% CI = 0.86 to 1.02), 0.88 (95% CI = 0.81 to 0.96), and 0.85 (95% CI = 0.78 to 0.94), respectively (P(trend)<.001). Calcium intake was also inversely related to the risk of colorectal cancer. The relative risk for the highest versus the lowest quintile of intake was 0.86 (95% CI = 0.78 to 0.95; P(trend) =.02) for dietary calcium and 0.78 (95% CI = 0.69 to 0.88; P(trend)<.001) for total calcium (combining dietary and supplemental sources). These results were consistent across studies and sex. The inverse association for milk was limited to cancers of the distal colon (P(trend)<.001) and rectum (P(trend) =.02). CONCLUSION: Higher consumption of milk and calcium is associated with a lower risk of colorectal cancer.

Adenoma↗

Polymorphisms in the one-carbon metabolic pathway, plasma folate levels and colorectal cancer in a prospective study.

One-carbon (e.g., folate) metabolism plays a pivotal role in the etiology of colorectal cancer (CRC). Cytosolic serine hydroxymethyltransferase (cSHMT), methylenetetrahydrofolate dehydrogenase (MTHFD1) and glutamate carboxypeptidase II (GCPII) are key genes involved in this pathway. Several new polymorphisms have been identified and there is evidence implicating their functionality. We examined whether polymorphisms in these genes, i.e., cSHMT L474F, MTHFD1 R653Q and GCPII H475Y, modify the risk of CRC in the prospective Physicians' Health Study. Among the 270 incident CRC cases and 453 controls, none of the one-carbon polymorphisms were associated with risk of CRC. Compared to the wild-type genotype, the multivariate-adjusted relative risks and 95% confidence intervals were 1.14 [0.68, 1.93] for cSHMT 474FF, 1.04 [0.67, 1.62] for MTHFD1 653QQ and 1.00 [0.55, 1.82] for GCPII 474HY. Furthermore, we examined the associations between one-carbon polymorphisms and folate status in terms of plasma folate and homocysteine levels in this population. No independent gene effect was observed. Although compound homozygous variants at cSHMT and MTHFD1 loci had the lowest plasma folate levels compared to other compound genotypes, no significant gene-gene interactions were observed. Findings from our prospective investigation indicate that these newly identified polymorphisms in one-carbon metabolizing genes have limited functionality in modifying folate status and related CRC risk.

Adult↗

A randomized trial of multivitamin supplements and HIV disease progression and mortality.

BACKGROUND: Results from observational studies suggest that micronutrient status is a determinant of the progression of human immunodeficiency virus (HIV) disease. METHODS: We enrolled 1078 pregnant women infected with HIV in a double-blind, placebo-controlled trial in Dar es Salaam, Tanzania, to examine the effects of daily supplements of vitamin A (preformed vitamin A and beta carotene), multivitamins (vitamins B, C, and E), or both on progression of HIV disease, using survival models. The median follow-up with respect to survival was 71 months (interquartile range, 46 to 80). RESULTS: Of 271 women who received multivitamins, 67 had progression to World Health Organization (WHO) stage 4 disease or died--the primary outcome--as compared with 83 of 267 women who received placebo (24.7 percent vs. 31.1 percent; relative risk, 0.71; 95 percent confidence interval, 0.51 to 0.98; P=0.04). This regimen was also associated with reductions in the relative risk of death related to the acquired immunodeficiency syndrome (0.73; 95 percent confidence interval, 0.51 to 1.04; P=0.09), progression to WHO stage 4 (0.50; 95 percent confidence interval, 0.28 to 0.90; P=0.02), or progression to stage 3 or higher (0.72; 95 percent confidence interval, 0.58 to 0.90; P=0.003). Multivitamins also resulted in significantly higher CD4+ and CD8+ cell counts and significantly lower viral loads. The effects of receiving vitamin A alone were smaller and for the most part not significantly different from those produced by placebo. Adding vitamin A to the multivitamin regimen reduced the benefit with regard to some of the end points examined. CONCLUSIONS: Multivitamin supplements delay the progression of HIV disease and provide an effective, low-cost means of delaying the initiation of antiretroviral therapy in HIV-infected women.

AIDS-Related Opportunistic Infections↗

A prospective study of dietary lactose and ovarian cancer.

The milk sugar lactose is an hypothesized risk factor for epithelial ovarian cancer because of possible direct toxic effects of its metabolites on oocytes or by compensatory gonadotropin stimulation. Women are presently encouraged to consume dairy products as a source of calcium to prevent osteoporosis. The objective of our study was to prospectively assess lactose, milk and milk product consumption in relation to ovarian cancer risk among 80326 participants in the Nurses' Health Study who had no history of cancer other than nonmelanoma skin cancer. Participants in the Nurses' Health Study reported on known and suspected ovarian cancer risk factors in questionnaires mailed biennially from 1976 to 1996. Food frequency questionnaires were included in the years 1980, 1984, 1986 and 1990. Newly reported ovarian cancer was documented by review of medical records. During 16 years of follow-up (1980-1996), 301 cases of invasive epithelial ovarian cancer were confirmed. Pooled logistic regression was used to control for age, body mass index (kg/m(2)), caffeine intake, oral contraceptive use, smoking history, parity and tubal ligation. For all subtypes of invasive ovarian cancer combined, we observed a nonsignificant 40% greater risk for women in the highest category of lactose consumption compared to the lowest (multivariate relative risk (RR) 1.40, 95% confidence interval (CI), 0.98-2.01). We observed a 2-fold higher risk of the serous ovarian cancer subtype among those in the highest category of lactose consumption compared to the lowest (RR 2.07, 95% CI, 1.27-3.40). For each 11-gram increase in lactose consumption (the approximate amount in one glass of milk), we observed a 20% increase in risk of serous cancers (RR 1.20, 95% CI, 1.04-1.39). Skim and low-fat milk were the largest contributors to dietary lactose. Women who consumed one or more servings of skim or low-fat milk daily had a 32% higher risk of any ovarian cancer (RR 1.32, 95% CI, 0.97-1.82) and a 69% higher risk of serous ovarian cancer (RR 1.69, 95% CI, 1.12-2.56) compared to women consuming 3 or less servings monthly. Controlling for fat intake did not change our findings. Our findings provide some support for the hypothesis that lactose intake increases risk of epithelial ovarian cancer. However, the observed excess risk appeared limited to the serous subtype of ovarian cancer in our study.

Adult↗

Common ataxia telangiectasia mutated haplotypes and risk of breast cancer: a nested case-control study.

INTRODUCTION: The ataxia telangiectasia mutated (ATM) gene is a tumor suppressor gene with functions in cell cycle arrest, apoptosis, and repair of DNA double-strand breaks. Based on family studies, women heterozygous for mutations in the ATM gene are reported to have a fourfold to fivefold increased risk of breast cancer compared with noncarriers of the mutations, although not all studies have confirmed this association. Haplotype analysis has been suggested as an efficient method for investigating the role of common variation in the ATM gene and breast cancer. Five biallelic haplotype tagging single nucleotide polymorphisms are estimated to capture 99% of the haplotype diversity in Caucasian populations. METHODS: We conducted a nested case-control study of breast cancer within the Nurses' Health Study cohort to address the role of common ATM haplotypes and breast cancer. Cases and controls were genotyped for five haplotype tagging single nucleotide polymorphisms. Haplotypes were predicted for 1309 cases and 1761 controls for which genotype information was available. RESULTS: Six unique haplotypes were predicted in this study, five of which occur at a frequency of 5% or greater. The overall distribution of haplotypes was not significantly different between cases and controls (chi2 = 3.43, five degrees of freedom, P = 0.63). CONCLUSION: There was no evidence that common haplotypes of ATM are associated with breast cancer risk. Extensive single nucleotide polymorphism detection using the entire genomic sequence of ATM will be necessary to rule out less common variation in ATM and sporadic breast cancer risk.

Adult↗

Polymorphisms in DNA double-strand break repair genes and skin cancer risk.

UV can cause a wide range of DNA lesions. UVA-induced oxidative DNA damage and blocked DNA replication by UVB-induced photoproducts can lead to double-strand breaks (DSBs). We selected 11 haplotype-tagging single nucleotide polymorphisms in three DSB repair genes XRCC2, XRCC3, and LigaseIV and evaluated their associations with skin cancer risk in a nested case-control study within the Nurses' Health Study [219 melanoma, 286 squamous cell carcinoma (SCC), 300 basal cell carcinoma (BCC), and 873 controls]. We observed that the XRCC3 18085T (241Met) allele and its associated haplotype were significantly inversely associated with the risks of SCC and BCC, whereas the XRCC3 4552C allele along with its associated haplotype and the XRCC2 30833A allele were significantly associated with increased BCC risk. The LigaseIV 4044T and 4062T alleles were associated with decreased BCC risk; two of four haplotypes were significantly associated with altered BCC risk. A trend toward decreased risk of nonmelanoma skin cancer was found in those harboring a greater number of putative low risk alleles (P for trend, 0.05 for SCC, <0.0001 for BCC). The main effects of these genotypes were essentially null for melanoma risk. This study provides evidence to suggest the role of the DSB repair pathway in skin cancer development, especially for BCC.

Adult↗

Alcohol intake and colorectal cancer: a pooled analysis of 8 cohort studies.

BACKGROUND: Epidemiologic studies have generally reported positive associations between alcohol consumption and risk for colorectal cancer. However, findings related to specific alcoholic beverages or different anatomic sites in the large bowel have been inconsistent. OBJECTIVE: To examine the relationship of total alcohol intake and intake from specific beverages to the incidence of colorectal cancer and to evaluate whether other potential risk factors modify the association. DESIGN: Pooled analysis of primary data from 8 cohort studies in 5 countries. SETTING: North America and Europe. PARTICIPANTS: 489,979 women and men with no history of cancer other than nonmelanoma skin cancer at baseline. MEASUREMENTS: Alcohol intake was assessed in each study at baseline by using a validated food-frequency questionnaire. RESULTS: During a maximum of 6 to 16 years of follow-up across the studies, 4687 cases of colorectal cancer were documented. In categorical analyses, increased risk for colorectal cancer was limited to persons with an alcohol intake of 30 g/d or greater (approximately > or =2 drinks/d), a consumption level reported by 4% of women and 13% of men. Compared with nondrinkers, the pooled multivariate relative risks were 1.16 (95% CI, 0.99 to 1.36) for persons who consumed 30 to less than 45 g/d and 1.41 (CI, 1.16 to 1.72) for those who consumed 45 g/d or greater. No significant heterogeneity by study or sex was observed. The association was evident for cancer of the proximal colon, distal colon, and rectum. No clear difference in relative risks was found among specific alcoholic beverages. LIMITATIONS: The study included only one measure of alcohol consumption at baseline and could not investigate lifetime alcohol consumption, alcohol consumption at younger ages, or changes in alcohol consumption during follow-up. It also could not examine drinking patterns or duration of alcohol use. CONCLUSIONS: A single determination of alcohol intake correlated with a modest relative elevation in colorectal cancer rate, mainly at the highest levels of alcohol intake.

Adult↗

Dietary carbohydrates, fiber, and breast cancer risk.

Dietary fiber, fiber fractions, carbohydrate, glycemic index, and glycemic load were prospectively assessed five times over 18 years with a validated food frequency questionnaire in relation to breast cancer risk among 88,678 women (aged 34-59 years at baseline) in the Nurses' Health Study. Incident breast cancer occurred in 4,092 of these women between 1980 and 1998. The authors observed no material association between carbohydrate intake, glycemic index and glycemic load, total dietary fiber intake, and breast cancer risk. The relative risks for the highest versus the lowest quintile of intake were 0.97 (95% confidence interval (CI): 0.87, 1.08) for carbohydrates, 1.08 (95% CI: 0.97, 1.19) for glycemic index, 0.99 (95% CI: 0.89, 1.10) for glycemic load, and 0.98 (95% CI: 0.87, 1.11) for fiber. The relative risk comparing those in the highest 0.7% of fiber intake (>30 g/day) with those in the lowest 10% of fiber intake (< or =10 g/day) was 0.68 (95% CI: 0.43, 1.06). Analyses stratified by menopausal status and body mass index also showed no clear risk pattern. In this cohort of middle-aged women, no overall association was found for dietary carbohydrates, glycemic index and glycemic load, and breast cancer risk. This study also confirmed the lack of an overall association between intake of fiber and fiber types and breast cancer risk observed in other prospective studies.

Adult↗

Epoxide hydrolase polymorphisms, cigarette smoking and risk of colorectal adenoma in the Nurses' Health Study and the Health Professionals Follow-up Study.

Microsomal epoxide hydrolase (mEH) is involved in the bioactivation and detoxification of polycyclic aromatic hydrocarbons derived from tobacco smoke and charred meat intake. Two coding region mEH variants located in exon 3 (Tyr113His) and exon 4 (His139Arg) have been described and may affect the enzyme's specific activity. We investigated these polymorphisms and tested interactions with smoking and charred meat intake in relation to risk of colorectal adenoma in two case-control studies nested in the Nurses' Health Study (NHS) and Health Professionals Follow-up Study (HPFS) cohorts. mEH exon 3 and exon 4 polymorphisms were not associated with overall risk of adenoma among 556 incident cases and 557 controls from the NHS or 376 prevalent cases and 725 controls from the HPFS. A statistically significant interaction was found between the exon 4 polymorphism and smoking for men (P = 0.03) and a borderline significant interaction was found between the exon 3 polymorphism and smoking for women (P = 0.06). Women having the exon 3 'rapid' Tyr/Tyr genotype were at increased risk when exposed to either > or =25 pack-years smoking [relative risk (RR) = 2.43, 95% confidence interval (CI) 1.47-4.01] or <25 pack-years of smoking (RR = 1.73, 95% CI 1.10-2.73) relative to non-smokers. Men with the exon 4 'slow' His/His genotype were at increased risk when exposed to > or =25 pack-years smoking (RR = 2.21, 95% CI 1.43, 3.41) or <25 pack-years smoking (RR = 1.71, 95% CI 1.13-2.59) relative to non-smokers. Charred meat intake was not associated with adenoma risk and there was no significant interaction with either mEH polymorphism. Our results indicate that individuals exposed to > or =25 pack-years smoking were at increased risk for colorectal adenoma and that risk is related to dose of tobacco carcinogens and mEH activity level, but the results were not consistent between men and women.

Adenoma↗

A prospective study of aspirin use and the risk for colorectal adenoma.

BACKGROUND: Randomized, double-blind, placebo-controlled trials have established that regular aspirin use reduces the risk for recurrent colorectal adenoma. However, the effect of dose and duration of use, particularly in an average-risk population, is not well understood. OBJECTIVE: To examine the influence of dose and duration of aspirin use in the primary prevention of colorectal adenoma. DESIGN: Prospective cohort study. SETTING: Nurses' Health Study. PARTICIPANTS: 27 077 women, 34 to 77 years of age, without a history of adenoma, cancer, inflammatory bowel disease, or familial polyposis, who underwent lower endoscopy between 1980 and 1998. MEASUREMENTS: 1368 cases of confirmed distal colorectal adenoma were diagnosed between 1980 and 1998. Self-reported data on aspirin use were collected from biennial questionnaires. RESULTS: After other risk factors for adenoma were adjusted, women who regularly used aspirin (> or =2 standard aspirin tablets/wk) had a multivariate relative risk for adenoma of 0.75 (95% CI, 0.66 to 0.84) compared with nonregular users. Compared with women who denied any aspirin use, the multivariate relative risks for adenoma were 0.80 (CI, 0.70 to 0.93) for women who used 0.5 to 1.5 standard tablets per week, 0.74 (CI, 0.62 to 0.88) for those who used 2 to 5 tablets per week, 0.72 (CI, 0.61 to 0.85) for those who used 6 to 14 tablets per week, and 0.49 (CI, 0.36 to 0.65) for those who used more than 14 tablets per week (P < 0.001 for trend). Similar dose-response relationships were found among regular short-term users (< or =5 years; P < 0.001) and long-term users (>5 years; P < 0.001). In contrast, after adjustments were made for dose, increasing duration of aspirin use did not confer greater risk reduction (P > 0.2). CONCLUSIONS: Regular, short-term use of aspirin is inversely associated with risk for colorectal adenoma. However, the greatest protective effect is evident at substantially higher doses (>14 tablets/wk) than those recommended for the prevention of cardiovascular disease. Before aspirin can be recommended for chemoprevention in the general adult population, these results suggest the need for a more thorough evaluation of the risks and benefits of routine aspirin use at doses not previously considered.

Adenoma↗

The functional UGT1A1 promoter polymorphism decreases endometrial cancer risk.

UDP-glucuronosyltransferase (UGT) 1A1 is involved in the inactivation of estradiol (E(2)) and its oxidized metabolites. These metabolites have been shown to contribute to the development of endometrial cancer in animal studies. Thus UGT1A1 represents a candidate gene in endometrial carcinogenesis. In this study, we established the substrate specificity of UGT1A1 for E(2) and its 2- and 4-hydroxylated metabolites. Intrinsic clearances indicated that UGT1A1 had a preference for the glucuronidation of 2-hydroxyestradiol, a metabolite associated with antiproliferative activity. Expression analysis demonstrated that UGT1A1 is present in the nonmalignant endometrium. Subsequently, we sought to determine whether the common UGT1A1 promoter allele, UGT1A1*28 [A(TA)(7)TAA], which decreases gene transcription, was associated with endometrial cancer risk in a case-control study nested within the Nurses' Health Study (222 cases, 666 matched controls). Conditional logistic regression demonstrated a significant inverse association with the UGT1A1*28 allele and endometrial cancer risk. Compared with women homozygous for the UGT1A1*1 [A(TA)(6)TAA] allele, the adjusted odds ratio (OR) was 0.81 [95% confidence interval (CI), 0.56-1.16] for the UGT1A1*1/*28 genotype and 0.40 (95% CI, 0.21-0.75) for the homozygous UGT1A1*28 genotype (P(trend) = 0.007). There was a suggestion of an interaction by menopausal status [OR = 0.39 (95% CI, 0.18-0.85) for premenopausal women and OR = 0.79 (95% CI, 0.55-1.13) for postmenopausal women who carry the UGT1A1*28 allele (P(interaction) = 0.05)]. These observations suggest that lower expression of UGT1A1 decreases the risk of endometrial cancer by reducing the excretion of 2-hydroxyestradiol, the antiproliferative metabolite of E(2), in the endometrium.

Adult↗

Association of squatting with increased prevalence of radiographic tibiofemoral knee osteoarthritis: the Beijing Osteoarthritis Study.

OBJECTIVE: To examine the association between squatting, a common daily posture in China, and the prevalence of radiographic osteoarthritis (OA) in different knee compartments among Chinese subjects from Beijing, and to estimate how much of the difference in prevalence of knee OA between Chinese subjects in Beijing and white subjects in Framingham, Massachusetts is accounted for by the impact of squatting. METHODS: We recruited a random sample of Beijing residents age > or =60 years. Subjects answered questions on joint symptoms, and knee radiographs were obtained. Subjects were also asked to recall the average amount of time spent squatting each day at age 25 years. Radiographic films (weight-bearing anteroposterior and skyline views) were read for Kellgren/Lawrence (K/L) grade and individual radiographic features. Medial disease was defined when radiographs showed a K/L grade of > or =2 at the tibiofemoral joint and a medial joint space narrowing score of > or =1, and lateral disease was assessed in a comparable manner in the lateral compartments. We examined the association of squatting with the prevalence of tibiofemoral OA as well as with the prevalence of patellofemoral knee OA, while adjusting for age and other potential confounding factors. We used the same approach to assess the relationship between squatting and tibiofemoral OA in the medial compartment and in the lateral compartment. Finally, we estimated the impact of squatting at age 25 on the difference in prevalence of knee OA between Chinese subjects in Beijing and white subjects in the Framingham OA Study. RESULTS: Squatting was very common among the Chinese subjects: approximately 40% of men and approximately 68% of women reported squatting > or =1 hour per day at age 25. The prevalence of tibiofemoral OA increased as the time spent squatting at age 25 increased in both the men and the women. Compared with subjects who squatted <30 minutes per day at age 25, the multivariable-adjusted prevalence odds ratios of tibiofemoral OA were 1.1 for time spent squatting of 30-59 minutes/day, 1.0 for 60-119 minutes/day, 1.7 for 120-179 minutes/day, and 2.0 for > or =120 minutes/day among the men (P for trend = 0.074), and the respective odds ratios among the women were 1.4, 1.3, 1.2, and 2.4 (P for trend = 0.077). A weaker association with patellofemoral OA was found. Prolonged squatting in daily life was more strongly associated with medial knee OA than with lateral disease in the men, but had a similar effect on both knee compartments in the women. After adjusting for the impact of squatting, the age-adjusted difference in prevalence of tibiofemoral OA was reduced from an excess of 14.4% to 9.5% in the Chinese women, but the difference in prevalence of tibiofemoral OA in the Chinese men increased after adjustment for age and squatting, from 2.9% lower to 7.0% lower as compared with their white counterparts. CONCLUSION: Prolonged squatting is a strong risk factor for tibiofemoral knee OA among elderly Chinese subjects in Beijing, and accounts for a substantial proportion of the difference in prevalence of tibiofemoral OA between Chinese subjects in Beijing and white subjects in Framingham.

Aged↗

Chopstick arthropathy: the Beijing Osteoarthritis Study.

OBJECTIVE: Several investigators have speculated that mechanical stress might play an important role in the development of hand osteoarthritis (OA). Chopsticks, used universally as eating utensils in China, increase joint loading in the first through third fingers. We conducted a population-based survey among elderly Chinese individuals living in Beijing, to explore whether chopsticks use is associated with prevalent hand OA. METHODS: We recruited a sample of persons ages 60 years and older, using door-to-door enumeration in randomly selected neighborhoods in Beijing. Subjects answered questions about the hand with which they use chopsticks, handedness, and pincer grip activities. Bilateral posteroanterior hand radiographs were obtained, and each joint was graded according to the Kellgren/Lawrence (K/L) scale. We defined a subject as having radiographic OA if at least 1 of his or her hand joints had radiographic OA (K/L score of > or =2). We defined a particular hand group (i.e., distal interphalangeal [DIP] joints, proximal interphalangeal [PIP] joints, or metacarpophalangeal [MCP] joints) as having OA if at least 1 joint of the group had radiographic OA. We calculated the prevalence of OA for each hand joint and, according to the status of chopsticks use, performed a matched analysis to examine the relationship between chopsticks use and the prevalence of hand OA. In the analysis, we excluded persons who reported a previous hand injury. Because most subjects used chopsticks with their dominant hand (a hand they would be expected to use more for all manual tasks), we also performed the analysis among subjects who reported that they had no hand preference when performing other activities and subjects who denied other pincer grip activities. RESULTS: A total of 1,008 men and 1,499 women were assessed. The prevalence ratio for OA of the thumb IP joint in the chopsticks hand was 1.2 (range 1.1-1.4) in men and 1.6 (range 1.4-1.7) in women; the prevalence ratio for OA of the second and third PIP joints was 1.5 (range 1.1-2.2) in men and 1.4 (range 1.2-1.7) in women; and the prevalence ratio for OA of the second and third MCP joints was 1.4 (range 1.2-1.6) in men and 1.4 (range 1.2-1.6) in women. The prevalence ratios in these joints were greater than the ratios in other MCP, PIP, or DIP joints from the same hand that were unlikely to be involved by chopsticks use, especially among women. Similar results were observed when the analyses were limited to ambidextrous subjects and subjects who did not engage in any other pincer grip activities. Thumb IP joint OA affected 26% of the entire population studied, and chopsticks use accounted for 19% of the risk of OA developing in this joint in men and 36% of the risk in women. CONCLUSION: This epidemiologic study investigated the relationship of chopsticks use to hand arthropathy. The results suggest that chopsticks use is associated with an increased prevalence of OA in the IP joint of the thumb, and in the second and third PIP and MCP joints.

Aged↗

The effect of body weight on progression of knee osteoarthritis is dependent on alignment.

OBJECTIVE: Whereas obesity increases overall loading of the knee, limb malalignment concentrates that loading on a focal area, to the level at which cartilage damage may occur. This study evaluated whether the effect of body weight on progression of knee osteoarthritis (OA) differs depending on the degree of limb malalignment. METHODS: The study population comprised 228 veterans and community recruits with symptomatic knee OA (pain on most days and radiographic disease) who volunteered to participate in a natural history study and from whom baseline radiographs were obtained to assess alignment; 227 (99.6%) completed a 30-month followup. Of 403 knees assessed at baseline, 394 (97.8%) were followed up. Participants' body mass index (BMI) was assessed at each examination. The main outcome measure was progression of knee OA, defined as narrowing of the tibiofemoral joint space by 1 grade (semiquantitative scale 0-3) on radiographs of the fluoroscopically positioned knee. The association between BMI and the risk of knee OA progression was assessed after adjusting for age, sex, and limb alignment, using logistic regression and generalized estimating equations. RESULTS: Of 394 knees, 90 (22.8%) showed disease progression, and limb alignment was strongly associated with progression risk. The risk of progression increased with increasing weight (for each 2-unit increase in BMI, odds ratio [OR] for progression 1.08, 95% confidence interval [95% CI] 1.00-1.16). However, among those knees with neutral alignment (0-2 degrees ), increases in BMI had no effect on risk of progression (OR 1.00), and in those with severe malalignment (> or =7 degrees ), the effect was similarly null (OR 0.93). The effect of BMI on progression was limited to knees in which there was moderate malalignment (OR per 2-unit increase in BMI 1.23, 95% CI 1.05-1.45). CONCLUSION: Although elevated BMI increases the risk of knee OA progression, the effect of BMI is limited to knees in which moderate malalignment exists, presumably because of the combined focus of load from malalignment and the excess load from increased weight. This has implications for clinical recommendations and for trials testing weight loss in those with knee OA.

Aged↗

In utero exposures and the incidence of endometriosis.

OBJECTIVE: To investigate the relation between the fetal environment and endometriosis. DESIGN: Prospective cohort study. SETTING: Nurses' Health Study II with 10 years of follow-up. PARTICIPANT(S): Eighty-four thousand, four hundred forty-six women aged 25-42 who had never been diagnosed with endometriosis, infertility, or cancer at baseline in 1989. MAIN OUTCOME MEASURE(S): Incidence of laparoscopically confirmed endometriosis according to birthweight, prematurity, multiple gestation, diethylstilbestrol (DES) exposure, and having been breastfed. RESULT(S): During 566,250 woman-years of follow-up, 1,226 cases of laparoscopically-confirmed endometriosis were reported among women with no past infertility. After adjusting for age, calendar time, parity, race, and body mass index at age 18, we observed a linear increase in the incidence rate with decreasing birthweight (rate ratio [RR] = 1.3 for birthweight <5.5 pounds versus 7.0-8.4 pounds, 95% confidence interval [CI] = 1.0-1.8, P value, test for trend = .01). In addition, women who were born as one of a multiple gestation (i.e., twins or greater number) were at increased risk even after controlling for birthweight (RR = 1.7, CI = 1.2-2.5). The rate of endometriosis was also 80% greater among women exposed to diethylstilbestrol in utero (RR = 1.8, CI = 1.2-2.8). Neither premature delivery nor having been breastfed were associated with the incidence of endometriosis. None of these effect estimates were modified by infertility status at the time of endometriosis diagnosis. CONCLUSION(S): The fetal environment is associated with subsequent laparoscopically confirmed endometriosis in this cohort of US women.

Adult↗