Showing papers by "Frank E. Speizer published in 2000"

A prospective, observational study of postmenopausal hormone therapy and primary prevention of cardiovascular disease.

Abstract: Postmenopausal hormone use appears to decrease risk for major coronary events in women without previous heart disease. Furthermore, 0.3 mg of oral conjugated estrogen daily is associated with a red...

Pooled Analysis of Prospective Cohort Studies on Height, Weight, and Breast Cancer Risk

Abstract: The association between anthropometric indices and the risk of breast cancer was analyzed using pooled data from seven prospective cohort studies. Together, these cohorts comprise 337,819 women and 4,385 incident invasive breast cancer cases. In multivariate analyses controlling for reproductive, dietary, and other risk factors, the pooled relative risk (RR) of breast cancer per height increment of 5 cm was 1.02 (95% confidence interval (Cl): 0.96, 1.10) in premenopausal women and 1.07 (95% Cl: 1.03, 1.12) in postmenopausal women. Body mass index (BMI) showed significant inverse and positive associations with breast cancer among pre- and postmenopausal women, respectively; these associations were nonlinear. Compared with premenopausal women with a BMI of less than 21 kg/m2, women with a BMI exceeding 31 kg/m2 had an RR of 0.54 (95% Cl: 0.34, 0.85). In postmenopausal women, the RRs did not increase further when BMI exceeded 28 kg/m2; the RR for these women was 1.26 (95% Cl: 1.09, 1.46). The authors found little evidence for interaction with other breast cancer risk factors. Their data indicate that height is an independent risk factor for postmenopausal breast cancer; in premenopausal women, this relation is less clear. The association between BMI and breast cancer varies by menopausal status. Weight control may reduce the risk among postmenopausal women.

Prospective Study of Fruit and Vegetable Consumption and Risk of Lung Cancer Among Men and Women

Abstract: Background: Diets high in fruits and vegetables have been shown to be associated with a lower risk of lung cancer. -Carotene was hypothesized to be largely responsible for the apparent protective effect, but this hypothesis was not supported by clinical trials. Methods: We examined the association between lung cancer risk and fruit and vegetable consumption in 77 283 women in the Nurses’ Health Study and 47 778 men in the Health Professionals’ Follow-up Study. Diet was assessed with the use of a food-frequency questionnaire that included 15 fruits and 23 vegetables. We used logistic regression models to estimate relative risks (RRs) of lung cancer within each cohort. All statistical tests were two-sided. Results: We documented 519 lung cancer cases among the women and 274 among the men. Total fruit and vegetable consumption was associated with a modestly lower risk of lung cancer among the women but not among the men. The RR for the highest versus lowest quintile of intake was 0.79 (95% confidence interval [CI] = 0.59–1.06) among the women and 1.12 (95% CI = 0.74–1.69) among the men after adjustment for smoking status, quantity of cigarettes smoked per day, time since quitting smoking, and age at initiation of smoking. However, total fruit and vegetable consumption was associated with a lower risk of lung cancer among never smokers in the combined cohorts, although the reduction was not statistically significant (RR = 0.63; 95% CI = 0.35–1.12 in the highest tertile). Conclusion: Higher fruit and vegetable intakes were associated with lower risks of lung cancer in women but not in men. It is possible that the inverse association among the women remained confounded by unmeasured smoking characteristics, although fruits and vegetables were protective in both men and women who never smoked. [J Natl Cancer Inst 2000;92: 1812–23]

Prospective Study of Fruit and Vegetable Consumption and Incidence of Colon and Rectal Cancers

Abstract: Background Frequent consumption of fruit and vegetables has been associated with a reduced risk of colorectal cancer in many observational studies. Methods We prospectively investigated the association between fruit and vegetable consumption and the incidence of colon and rectal cancers in two large cohorts: the Nurses' Health Study (88 764 women) and the Health Professionals' Follow-up Study (47 325 men). Diet was assessed and cumulatively updated in 1980, 1984, 1986, and 1990 among women and in 1986 and 1990 among men. The incidence of cancer of the colon and rectum was ascertained up to June or January of 1996, respectively. Relative risk (RR) estimates were calculated with the use of pooled logistic regression models accounting for various potential confounders. All statistical tests were two-sided. Results With a follow-up including 1 743 645 person-years and 937 cases of colon cancer, we found little association of colon cancer incidence with fruit and vegetable consumption. For women and men combined, a difference in fruit and vegetable consumption of one additional serving per day was associated with a covariate-adjusted RR of 1.02 (95% confidence interval [CI] = 0.98-1.05). A difference in vegetable consumption of one additional serving per day was associated with an RR of 1.03 (95% CI = 0.97-1.09). Similar results were obtained for women and men considered separately. A difference in fruit consumption of one additional serving per day was associated with a covariate-adjusted RR for colon cancer of 0.96 (95% CI = 0.89-1.03) among women and 1. 08 (95% CI = 1.00-1.16) among men. For rectal cancer (total, 244 cases), a difference in fruit and vegetable consumption of one additional serving per day was associated with an RR of 1.02 (95% CI = 0.95-1.09) in men and women combined. None of these associations was modified by vitamin supplement use or smoking habits. Conclusions Although fruits and vegetables may confer protection against some chronic diseases, their frequent consumption does not appear to confer protection from colon or rectal cancer.

A Prospective Study of Plasma Insulin-like Growth Factor-1 and Binding Protein-3 and Risk of Colorectal Neoplasia in Women

Abstract: Insulin-like growth factor-1 (IGF-1) is an important mitogen, and IGF binding protein-3 (IGFBP-3) has opposing effects. Acromegalics, who have abnormally elevated levels of IGF-1, are at increased risk of colorectal tumors. Recent studies have found that IGF-1 levels correlate with risk of prostate cancer and colorectal cancer in men, premenopausal breast cancer in women, and lung cancer in men and women. We examined whether prediagnostic plasma levels of IGF-1 and IGFBP-3 influence risk of colorectal cancer and adenoma in women. From 1989 to 1990, a total of 32,826 women from the Nurses’ Health Study provided blood specimens that were archived in liquid nitrogen. During 6 years of follow-up from 1989 to 1994, we documented 79 new cases of colorectal cancer, 90 cases of intermediate/late-stage adenoma (≥1 cm or tubulovillous/villous histology), and 107 cases of early-stage adenoma (<1 cm and tubular histology). After matching controls (2:1 for cancers and 1:1 for adenomas) to cases by age, month of blood draw, fasting status, and indication for endoscopy (for adenoma controls), plasma IGF-1 and IGFBP-3 levels were measured. Controlling for IGFBP-3 level, relative to women in the low tertile of IGF-1, those in the high tertile were at elevated risk of intermediate/late-stage colorectal neoplasia adenoma [multivariate relative risk (RR), 2.78; 95% confidence interval (CI), 0.76–9.76] and cancer (RR, 2.18; 95% CI, 0.94–5.08). Controlling for IGF-1 level, relative to women in the low tertile of IGFBP-3, women in the high tertile of IGFBP-3 were at lower risk of intermediate/late-stage colorectal adenoma (RR, 0.28; 95% CI, 0.09–0.85) and cancer (RR, 0.28; 95% CI, 0.10–0.83). Neither IGF-1 nor IGFBP-3 had any appreciable relation with early-stage adenoma. These analyses indicate that high levels of circulating IGF-1 and particularly low levels of IGFBP-3 are associated independently with an elevated risk of large or tubulovillous/villous colorectal adenoma and cancer.

Trends in the Incidence of Coronary Heart Disease and Changes in Diet and Lifestyle in Women

Abstract: Background Previous studies have found concurrent declines in blood pressure, serum cholesterol levels, and the incidence of and mortality from coronary disease. However, the effects of changes in diet and lifestyle on trends in coronary disease are largely unknown. Methods We followed 85,941 women who were 34 to 59 years old and had no previously diagnosed cardiovascular disease or cancer from 1980 to 1994 in the Nurses' Health Study. Diet and lifestyle variables were assessed at base line and updated during follow-up. Results After adjustment for the effect of age, the incidence of coronary disease declined by 31 percent from the two-year period 1980–1982 to the two-year period 1992–1994. From 1980 to 1992, the proportion of participants currently smoking declined by 41 percent, the proportion of postmenopausal women using hormone therapy increased by 175 percent, and the prevalence of overweight, defined as a body-mass index (the weight in kilograms divided by the square of the height in meters) of 25 ...

Gender-related differences in severe, early-onset chronic obstructive pulmonary disease.

Abstract: Men have higher prevalence rates of chronic obstructive pulmonary disease (COPD) than women, which has been attributed to the historically higher rates of cigarette smoking in males. However, the increased rates of cigarette smoking in females within the last several decades have been associated with steadily increasing rates of COPD in women. As part of a study of the genetics of severe, early-onset COPD, we assembled a group of 84 probands with severe, early-onset COPD (without severe alpha(1)-antitrypsin deficiency) and 348 of their first-degree relatives. We found a markedly elevated prevalence (71.4%) of females among the early-onset COPD probands. Among the entire group of first-degree relatives of early-onset COPD probands, univariate analysis demonstrated similar spirometric values and bronchodilator responsiveness in males and females; however, among current or ex-smokers, female first-degree relatives had significantly lower FEV(1)/ FVC (81.4 +/- 17.2% in females versus 87.0 +/- 12.9% in males, p = 0.009) and significantly greater bronchodilator responsiveness (expressed as percentage of baseline FEV(1)) (7.7 +/- 9.4% pred in females versus 4.1 +/- 6.4% pred in males, p = 0.002). Female smoking first-degree relatives were significantly more likely to demonstrate profound reductions in FEV(1) (< 40% pred) than male smoking first-degree relatives (p = 0. 03). Multivariate analysis, performed with generalized estimating equations, demonstrated that current or ex-smoking female first-degree relatives had significantly greater risk of FEV(1) < 80% pred (OR 1.91, 95% CI 1.03- 3.54), FEV(1) < 40% pred (OR 3.56, 95% CI 1.08-11.71), and bronchodilator response greater than 10% of baseline FEV(1) (OR 4.74, 95% CI 1.91-11.75). These results suggest that women may be more susceptible to the development of severe COPD.

Plasma Insulin-like Growth Factor (IGF) I, IGF-binding Protein 3, and Mammographic Density

Abstract: Insulin-like growth factors (IGFs) and insulin-like growth factor-binding proteins (IGFBPs) play a role in the normal development of breast tissue and possibly in the etiology of breast cancer. Breast density is one of the strongest predictors of breast cancer. In a cross-sectional analysis within the Nurses' Health Study, we compared the associations of plasma levels of endogenous IGF-I and IGFBP-3 with breast density in 65 premenopausal and 192 postmenopausal women. The digitized film screen mammograms were evaluated by the computer-assisted Toronto method, in which visually selected gray-scale cut points are used to assess breast density. Generalized linear models and Spearman's partial correlation coefficients described the associations between breast density and IGF-I, IGFBP-3, and the IGF-I:IGFBP-3 ratio. Premenopausal breast density was positively correlated with IGF-I and inversely correlated with IGFBP-3; the association was strongest for the IGF-I:IGFBP-3 ratio and breast density (r = 0.39; P = 0.004). In contrast, the correlation between breast density and the IGF-I:IGFBP-3 ratio among postmenopausal women was -0.02 (P = 0.83). The associations of IGF-I:IGFBP-3 ratio with breast density differed significantly between premenopausal and postmenopausal women (P = 0.01). Mammographic density is positively associated with plasma IGF-I levels and inversely associated with plasma IGFBP-3 levels among premenopausal women, but not among postmenopausal women. These results are consistent with previous studies that showed a positive association between a higher IGF-I:IGFBP-3 ratio and subsequent risk of breast cancer only among premenopausal women. The findings raise the possibility that premenopausal levels of IGF-I and IGFBP-3 could be in the etiological pathway that relates higher breast density with increased breast cancer risk.

A Prospective Study of Walking as Compared with Vigorous Exercise in the Prevention of Coronary Heart Disease in Women

Abstract: Background The role of walking, as compared with vigorous exercise, in the prevention of coronary heart disease remains controversial, and data for women on this topic are sparse. Methods We prospectively examined the associations between the score for total physical activity, walking, and vigorous exercise and the incidence of coronary events among 72,488 female nurses who were 40 to 65 years old in 1986. Participants were free of diagnosed cardiovascular disease or cancer at the time of entry and completed serial detailed questionnaires about physical activity. During eight years of follow-up, we documented 645 incident coronary events (nonfatal myocardial infarction or death from coronary disease). Results There was a strong, graded inverse association between physical activity and the risk of coronary events. As compared with women in the lowest quintile group for energy expenditure (expressed as the metabolic-equivalent [MET] score), women in increasing quintile groups had age-adjusted relative risks of 0.77, 0.65, 0.54, and 0.46 for coronary events (P for trend or =6 MET) was associated with similar risk reductions (30 to 40 percent). Sedentary women who became active in middle adulthood or later had a lower risk of coronary events than their counterparts who remained sedentary. Conclusions These prospective data indicate that brisk walking and vigorous exercise are associated with substantial and similar reductions in the incidence of coronary events among women.

Moderate Alcohol Consumption and Risk of Coronary Heart Disease Among Women With Type 2 Diabetes Mellitus

Abstract: Background—Moderate alcohol consumption is associated with reduced risk for coronary heart disease (CHD) in generally healthy populations. We assessed prospectively the association between moderate alcohol intake and CHD risk in women with type 2 diabetes mellitus, a group at high risk for cardiovascular disease. Methods and Results—We studied women in the Nurses’ Health Study who reported a diagnosis of diabetes mellitus at ≥30 years of age. During 39 092 person-years of follow-up from 1980 to 1994, there were 295 CHD events documented among this population, including 194 cases of nonfatal myocardial infarction and 101 cases of fatal CHD. Odds ratios derived from logistic regression were used to estimate relative risks (RRs) for CHD as a function of usual alcohol intake, with adjustment for potential confounders. Compared with diabetic women reporting no alcohol intake, the age-adjusted RR for nonfatal or fatal CHD among diabetic women reporting usual intake of 0.1 to 4.9 g (<0.5 drinks) of alcohol daily...

Intakes of fruits, vegetables, and related nutrients and the risk of non-Hodgkin's lymphoma among women.

Abstract: Non-Hodgkin's lymphoma is etiologically related to suppressed immune status, and certain nutrients found in fruits and vegetables have been associated with increased immune responses. However, limited information exists on associations between intake of fruits, vegetables, and related nutrients and non-Hodgkin's lymphoma risk. We thus examined these associations among 88,410 women in the Nurses' Health Study cohort who were aged 34-60 years in 1980 and provided dietary information in 1980. During 14 years of follow-up, we documented 199 incident cases of non-Hodgkin's lymphoma. Higher intake of fruits and vegetables was associated with a lower risk of non-Hodgkin's lymphoma (P for trend = 0.02); the multivariate relative risk (RR) was 0.62 [95% confidence interval (CI), 0.38-1.02] for women who consumed greater than or equal to six servings per day as compared with those consuming less than three servings per day. When fruits and vegetables were examined separately, intake of vegetables rather than fruits was most clearly associated with a reduced risk (P for trend = 0.02 for vegetables; P for trend = 0.16 for fruits); compared with those consuming less than one serving per day, the multivariate RRs were 0.62 (95% CI, 0.35-1.07) for women who consumed greater than or equal to three servings per day of vegetables and 0.70 (95% CI, 0.44-1.12) for women who consumed this amount of fruits. Higher intake of cruciferous vegetables was also associated with a decreased risk (P for trend = 0.03); the multivariate RR was 0.67 (95% CI, 0.40-1.11) for women who consumed greater than or equal to five servings per week as compared with those consuming less than two servings per week. These associations were slightly attenuated when we additionally adjusted for intake of beef, pork, or lamb as a main dish. Intake of dietary fiber from vegetable sources was related to a reduced risk; the multivariate RR was 0.54 (95% CI, 0.34-0.87) for women in the highest quintile as compared with those in the lowest quintile (P for trend = 0.01), and it was slightly attenuated with additional adjustment for saturated and trans unsaturated fats. However, we observed no associations between intakes of specific dietary carotenoids, vitamins A, C, E, and folate, and non-Hodgkin's lymphoma risk. Higher intake of vegetables, particularly cruciferous vegetables, may reduce the risk of non-Hodgkin's lymphoma among women.

A tetranucleotide repeat polymorphism in CYP19 and breast cancer risk.

Abstract: The CYP19 gene codes for aromatase, a key steroidogenic enzyme involved in the conversion of androgens to estrogens. A tetranucleotide (TTTA) repeat polymorphism is present in intron 4 of CYP19; 2 out of 4 breast cancer case-control studies have reported a greater frequency of 2 specific alleles among affected women. We evaluated associations between CYP19 repeat alleles and breast cancer risk in a case-control study nested within the Nurses' Health Study cohort (incident cases: n=462; controls: n=618). We observed seven different CYP19 alleles (TTTA(7-13)). Compared to controls, cases had a statistically significant greater frequency of the 10 (TTTA)(10) repeat allele (10 allele: 2.3% vs. 0.7%, p = 0.005) and a nonsignificant increase in the frequency of the 12 (TTTA)(12) allele (12 allele: 3.1% vs. 2.1%, p = 0.11). A higher frequency of the 10 allele was observed in more advanced cancer cases defined as four or more involved nodes or distant metastasis [4+ nodes: 5/36 (13.9%) vs. 0-3 nodes: 13/330 (3.9%), p = 0.02]. Among controls, we found women with the 7 repeat allele to have decreased levels of estrone sulfate (-16.4%, p = 0.02), estrone (-6.1%, p = 0.22) and estradiol (-9.9%, p = 0.10), and a lower estrone/androstenedione ratio (E1/A) (-10.5%, p = 0.08) compared to non-carriers. A higher E1/A ratio and elevated estrogen levels were observed among carriers of the 8 repeat allele; E1/A ratio (+21.0%, p = 0.003), estrone (+7.5%, p = 0.16) and estradiol (+10.8%, p = 0.08). However, we observed no evidence of an association between these alleles and breast cancer risk. We were unable to make inferences regarding the effect of the 10 allele on hormone levels due to the small number of allele carriers in the subgroup with hormone levels. As this repeat polymorphism is not close to the splice sites in intron 4, linkage disequilibrium with other functional polymorphisms in CYP19 may explain the findings of an increased association between breast cancer and the 10 allele variant of CYP19. We did not detect any sequence variants in the regulatory region or in the adipose-specific exon I.4. The lack of an established effect on CYP19 function associated with the 10 allele means that these findings should be interpreted with caution.

Plasma 1,25-Dihydroxy- and 25-Hydroxyvitamin D and Adenomatous Polyps of the Distal Colorectum

Abstract: 1,25-dihydroxyvitamin D [1,25(OH)2D] inhibits proliferation and promotes differentiation of human colon cancer cell lines. Epidemiological findings, although not entirely consistent, suggest an inverse relationship between vitamin D intake and colorectal cancer and adenoma, colorectal cancer precursor lesions. We evaluated the relationship of plasma 1,25(OH)2D and 25-hydroxyvitamin D [25(OH)D] with distal colorectal adenoma among 326 matched case and control pairs (nested in the prospective Nurses’ Health Study), who provided blood in 1989–1990 and who underwent endoscopy in 1989–1996. Plasma vitamin D metabolite concentrations were determined blindly by RIA. Odds ratios (ORs) and 95% confidence intervals (CIs) were estimated from multiple conditional logistic regression models. Mean plasma 1,25(OH)2D and 25(OH)D levels did not significantly differ ( P = 0.3 and 0.7, respectively) between cases (31.6 ± 8.4 pg/ml and 26.4 ± 10.6 ng/ml, respectively) and controls (32.2 ± 8.6 pg/ml and 26.8 ± 10.2 ng/ml, respectively). However, women whose plasma 1,25(OH)2D concentration was below 26.0 pg/ml (a level typically considered to be below normal) were at increased risk of distal colorectal adenoma (OR, 1.58; 95% CI, 1.03–2.40). Compared with the lowest 1,25(OH)2D quartile, women in the second (OR, 0.64; 95% CI, 0.41–1.02), third (OR, 0.80; 95% CI, 0.50–1.30), or upper (OR, 0.71; 95% CI, 0.43–1.15) quartiles were at a statistically nonsignificant lower risk of adenoma. The relationship was stronger for large/villous adenoma and among those with consistent vitamin D intake over the 10 years prior to blood draw. Compared with women in the lowest quartile, for plasma 25(OH)D, women in the second (OR, 0.64; 95% CI, 0.41–1.00) and third (OR, 0.58; 95% CI, 0.36–0.95) quartiles were at a statistically significantly lower risk of distal colorectal adenoma, but there was no difference in risk in the top quartile (OR, 1.04; 95% CI, 0.66–1.66). We conclude that women who have low levels of circulating 1,25(OH)2D may be at higher risk of distal colorectal adenomas, but additional study is warranted.

A tetranucleotide repeat polymorphism inCYP19 and breast cancer risk

Abstract: The CYP19 gene codes for aromatase, a key steroidogenic enzyme involved in the conversion of androgens to estrogens. A tetranucleotide (TTTA) repeat polymorphism is present in intron 4 of CYP19; 2 out of 4 breast cancer case‐control studies have reported a greater frequency of 2 specific alleles among affected women. We evaluated associations between CYP19 repeat alleles and breast cancer risk in a case‐control study nested within the Nurses' Health Study cohort (incident cases: n=462; controls: n=618). We observed seven different CYP19 alleles (TTTA7–13). Compared to controls, cases had a statistically significant greater frequency of the 10 (TTTA)10 repeat allele (10 allele: 2.3% vs. 0.7%, p = 0.005) and a nonsignificant increase in the frequency of the 12 (TTTA)12 allele (12 allele: 3.1% vs. 2.1%, p = 0.11). A higher frequency of the 10 allele was observed in more advanced cancer cases defined as four or more involved nodes or distant metastasis [4+ nodes: 5/36 (13.9%) vs. 0–3 nodes: 13/330 (3.9%), p = 0.02]. Among controls, we found women with the 7 repeat allele to have decreased levels of estrone sulfate (−16.4%, p = 0.02), estrone (−6.1%, p = 0.22) and estradiol (−9.9%, p = 0.10), and a lower estrone/androstenedione ratio (E1/A) (−10.5%, p = 0.08) compared to non‐carriers. A higher E1/A ratio and elevated estrogen levels were observed among carriers of the 8 repeat allele; E1/A ratio (+21.0%, p = 0.003), estrone (+7.5%, p = 0.16) and estradiol (+10.8%, p = 0.08). However, we observed no evidence of an association between these alleles and breast cancer risk. We were unable to make inferences regarding the effect of the 10 allele on hormone levels due to the small number of allele carriers in the subgroup with hormone levels. As this repeat polymorphism is not close to the splice sites in intron 4, linkage disequilibrium with other functional polymorphisms in CYP19 may explain the findings of an increased association between breast cancer and the 10 allele variant of CYP19. We did not detect any sequence variants in the regulatory region or in the adipose‐specific exon I.4. The lack of an established effect on CYP19 function associated with the 10 allele means that these findings should be interpreted with caution. Int. J. Cancer 87:204–210, 2000. © 2000 Wiley‐Liss, Inc.

Prospective Study of Talc Use and Ovarian Cancer

Abstract: Background: Perineal talc use has been associated with an increased risk of ovarian cancer in a number of case-control studies; however, this association remains controversial because of limited supporting biologic evidence and the potential for recall bias or selection bias in case-control studies. In this study, we conducted a prospective analysis of perineal talc use and the risk of ovarian cancer. Methods: The Nurses' Health Study is a prospective study of 121 700 female registered nurses in the United States who were aged 30-55 Sears at enrollment in 1976. Talc use was ascertained in 1982 by use of a self-administered questionnaire: after exclusions, 78 630 women formed the cohort for analysis. Three hundred seven epithelial ovarian cancers subsequently diagnosed in this cohort through June 1, 1996, were confirmed by medical-record review and met inclusion criteria. Proportional hazards models by use of pooled logistic regression were used to derive relative risks (RRs) and 95% confidence intervals (CIs), Results:: In 1982, 40.4% (n = 31 789) of the cohort reported ever using talc, and 14.5% (n = 11 411) reported ever using talc daily. We observed no overall association with ever talc use and epithelial ovarian cancer (multivariate RR = 1.09; 95% CI 0.86-1.37) and no increase in risk of ovarian cancer with increasing frequency of use. There was a modest elevation in risk for ever talc use and invasive serous ovarian cancer (multivariate RR = 1.40; 95% CI = 1.02-1.91), The risk of epithelial ovarian cancer for talc users was not greater among women who had never had a tubal ligation (multivariate RR = 0.97; 95% CI = 0.71-1.32). Conclusion: Our results provide little support for any substantial association between perineal talc use and ovarian cancer risk overall; however, perineal talc use may modestly increase the risk of invasive serous ovarian cancer.

Prospective study of alcohol consumption and the risk of age-related macular degeneration.

Abstract: Objective To describe the relationship between alcohol consumption and the incidence of age-related macular degeneration (AMD) Methods We conducted a prospective study among female nurses between 1980 and 1994 and among male health professionals between 1986 and 1994 We included 32,764 women and 29,488 men who were 50 years or older, without a diagnosis of AMD or cancer at baseline, and added additional subjects to the analysis as they reached 50 years of age Their alcohol intake was assessed at baseline and updated during follow-up evaluations using a validated semiquantitative food-frequency questionnaire After separate analyses for women and men, pooled estimates of the relationship of alcohol to the risk of AMD were calculated Results Age-related macular degeneration associated with a visual acuity loss of 20/30 or worse, including the early and dry and wet types, was diagnosed in 298 women (from 697,498 person-years of follow-up) and 153 men (229,180 person-years) by 1994, the end of follow-up After controlling for age, smoking, and other risk factors, the pooled relative risks (RRs) and 95% confidence intervals (CIs) for AMD compared with nondrinkers were 10 (07-12) for drinkers who consumed 01 to 49 g/d of alcohol; 09 (06-14) for 5 to 149 g/d; 11 (07-17) for 15 to 299 g/d; and 13 (09-18) for 30 g/d or more Among women, there was a suggestion of a modest increased risk of the disease in drinkers who consumed 30 g/d or more (RR, 15; 95% CI, 10-24); this was limited to an increased risk of the early and dry form (RR, 20; 95% CI, 12-34) No specific type of alcohol provided protection against AMD Conclusion This prospective study does not support an inverse relationship between moderate alcohol consumption and risk of AMD

Novel germline mutations in the PTEN tumour suppressor gene found in women with multiple cancers.

Abstract: Germline mutations in PTEN can predispose people to Cowden syndrome (CS) and Bannayan-Ruvalcaba-Riley (BRR) syndrome, rare, autosomal dominantly inherited neoplastic disorders. To determine whether germline mutations in PTEN contribute to genetic predisposition to multiple primary tumours within the general population, we conducted a nested case-control study, among 32 826 members of the prospective Nurses' Health Study cohort; cases were women with more than one primary tumour at different anatomical sites. We screened all nine exons of PTEN and flanking intronic splice sites for all 103 eligible cases using SSCP and sequencing. We observed two novel germline heterozygous missense mutations in exon 5 in five of the cases; three were V119L and two were V158L. Neither mutation was observed in 115 controls free of diagnosed cancer (p = 0.02). Both mutants showed partial tumour suppressor activity when compared to wild type PTEN when transfected into a PTEN null breast cancer cell line. The phenotype was cell line specific suggesting that genetic background affects growth suppression activity of the mutants. These data provide evidence that germline mutations in PTEN may be a more frequent predisposing factor for cancers in women than previously suggested.

Electric Blanket Use and Breast Cancer in the Nurses' Health Study

Abstract: Electric and magnetic fields (EMFs) have been hypothesized to increase the risk of breast cancer, and electric blankets represent an important source of exposure to EMFs. The authors examined the relation between electric blanket use and invasive breast cancer in the Nurses' Health Study. On the biennial questionnaire in 1992, 87,497 women provided information on this exposure during three consecutive time periods. In a prospective analysis with 301,775 person-years of follow-up through 1996 (954 cases), the relative risk for any electric blanket use was not elevated (relative risk (RR) = 1.08, 95% confidence interval (CI): 0.95, 1.24) after controlling for breast cancer risk factors. There was a weak association between breast cancer and electric blanket use at least 16 years before diagnosis and long-term use in age-adjusted analyses but not in multivariate models. In a retrospective analysis of 1,318,683 person-years of follow-up (2,426 cases), the multivariate relative risk associated with use before disease follow-up began was null (RR = 1.05, 95% CI: 0.95, 1.16). Similar results were obtained in analyses stratified by menopause and restricted to estrogen receptor-positive breast cancers. While 95% confidence intervals for these estimates did not exclude small risks, overall, results did not support an association between breast cancer risk and exposure to EMFs from electric blankets.

Diesel exhaust exposure and lung cancer: adjustment for the effect of smoking in a retrospective cohort study.

Abstract: Background The extent that cigarette smoking may confound the relationship between diesel exhaust exposure and lung cancer was assessed in a retrospective cohort study of 55,395 U.S. railroad workers followed from 1959 to 1976. Methods The relative risk (RR) of lung cancer due to diesel exhaust was indirectly adjusted using job-specific smoking data from a case-control study of railroad workers who died between 1981–1982 and from a survey of 514 living workers from an active railroad in 1982. Adjustment factors were developed based on the distribution of job-specific smoking rates. Results The unadjusted RR for lung cancer was 1.58 (95% CI = 1.14–2.20) for workers aged 40–44 in 1959, who experienced the longest possible duration of exposure, and the smoking adjusted RR was 1.44 (1.01–2.05). Conclusions After considering differences in smoking rates between workers exposed and unexposed to diesel exhaust in a relatively large blue-collar cohort, there were still elevated risks of lung cancer in workers in jobs with diesel exhaust exposure. Am. J. Ind. Med. 38:399–409, 2000. Published 2000 Wiley-Liss, Inc.

Polymorphic repeat in AIB1 does not alter breast cancer risk.

Abstract: We assessed the association between a glutamine repeat polymorphism in AIB1 and breast cancer risk in a case-control study (464 cases, 624 controls) nested within the Nurses' Health Study cohort. We observed no association between AIB1 genotype and breast cancer incidence, or specific tumor characteristics. These findings suggest that AIB1 repeat genotype does not influence postmenopausal breast cancer risk among Caucasian women in the general population.

Maximal and partial expiratory flow rates in a population sample of 10- to 11-yr-old schoolchildren. Effect of volume history and relation to asthma and maternal smoking.

Abstract: The effect of volume history on forced expiratory flow rates has been reported to differ between patients with asthma and healthy persons, and it has been hypothesized that the peripheral airway inflammation of patients with asthma may underlie this difference. There are no published data, however, on the distribution of such volume history effects or the relation of these effects to airways disease in children. We obtained combined partial and maximal forced expiratory flow–volume curves on 1,834 children, age 10–11 yr, in eight communities in the United States and Canada. The effect of a deep inhalation on forced expiratory flow rates at low lung volumes was quantitated by the ratio of V˙ 30 during a maximal expiratory maneuver (V˙ 30M) to V˙ 30 during a partial expiratory maneuver (V˙ 30P). The V˙ 30M/V˙ 30P ratio was slightly higher among girls than boys (1.26 versus 1.18, p = 0.0001) indicating that a deep inhalation increased V˙ 30 slightly more among girls than among boys. The V˙ 30M/V˙ 30P ratio w...

Occupational and environmental lung diseases: an overview.

Abstract: Chronic respiratory diseases other than lung cancer that are of occupational or environmental origin, along with cigarette smoking, account for over 100,000 deaths per year and are among the leading causes of respiratory disability in the United States and throughout the world. Lung cancer from these same exposures may account for 40,000 additional deaths per year. In spite of cigarette smoking's being recognized as the leading cause of both chronic obstructive pulmonary disease (COPD) and lung cancer, many other environmental and occupational exposures have been implicated as directly or indirectly associated with smoking in producing these diseases. In addition, the burden of disease is not uniformly distributed across the U.S. population. Furthermore, recognition of these associations with environmental and occupational exposures has done little in the last 20 years to reduce the burden of these respiratory conditions at the population level. COPD is the fourth leading cause of death in this country and, with asthma, accounts for one of the major categories of health care expenditure by whatever criteria are used. While the role of cigarette smoking is well characterized in these diseases as is the overwhelming role of smoking as the major cause of lung cancer, the identification of research objectives that could lead to strategies for lessening the burden of occupational and environmental causes of these chronic respiratory diseases is well worthwhile. For many years efforts to establish the number of people at risk in occupational settings have used estimates of employed and retired work forces in industries with known putative respiratory exposures. Often for legitimate reasons, developing these numbers has been extremely difficult, and thus the estimates are crude. Nevertheless, the National Institute for Occupational Safety and Health data suggest that over 20 million Americans are exposed to potential respiratory hazards in the workplace. Table 1 summarizes crude estimates of some of the major agents and industries in which exposures are known to occur. None of these exposures would be surprises to either the scientific community or the lay public, yet they continue to occur. Added to these numbers is the potential for over 100 million citizens to be exposed to environmental irritants from primary air pollutants that exceed the National Air Quality Standards first established by the U.S. Environmental Protection Agency in 1971 in many parts of the country at least several times per year. We approached this important topic by taking the view that it is critical to first understand the pathophysiologic, biologic, and general epidemiologic approaches that might be invoked in studying these diseases. Second, we explored the major environmental and occupational exposure patterns within the U.S. population. Finally, we selected the disease outcomes known to be associated with these exposures and asked experts to provide a selected review of the state of knowledge, to identify the important gaps in our knowledge, and to suggest avenues of research for the next 5-7 years. This effort brought together a wide variety of knowledgeable scientists with diverse expertise from basic science to clinical applications and population sciences. Although each manuscript in this monograph was produced independently, all authors had a common objective.

Insulin-like growth factors and mammographic density.

Abstract: Reprinted in Growth Hormone and IGF Research with permission from Elsevier. http://www.sciencedirect.com/science/journal/10966374