Alcohol consumption and risk of renal cell cancer: the NIH-AARP diet and health study.

BACKGROUND: The effect of moderate to heavy drinking (>15 g per day) on renal cell cancer (RCC) risk is unclear. METHOD: The relationship between alcohol consumption and RCC was examined in the NIH-AARP Diet and Health Study (n=49 2187, 1814 cases). RESULTS: Compared with >0 to <5 g per day of alcohol consumption, the multivariate relative risk (95% confidence intervals) for 15 to <30 and 30 g per day was, 0.75 (0.63-0.90) and 0.71 (0.59-0.85), respectively, in men and 0.67 (0.42-1.07) and 0.43 (0.22-0.84), respectively, in women. CONCLUSION: Alcohol consumption was inversely associated with RCC in a dose-response manner. The inverse association may be extended to 30 g per day of alcohol intake.

Physical activity, sedentary behaviours, and the prevention of endometrial cancer.

Physical activity has been hypothesised to reduce endometrial cancer risk, but this relationship has been difficult to confirm because of a limited number of prospective studies. However, recent publications from five cohort studies, which together comprise 2663 out of 3463 cases in the published literature for analyses of recreational physical activity, may help resolve this question. To synthesise these new data, we conducted a meta-analysis of prospective studies published through to December 2009. We found that physical activity was clearly associated with reduced risk of endometrial cancer, with active women having an approximately 30% lower risk than inactive women. Owing to recent interest in sedentary behaviour, we further investigated sitting time in relation to endometrial cancer risk using data from the NIH-AARP Diet and Health Study. We found that, independent of the level of moderate-vigorous physical activity, greater sitting time was associated with increased endometrial cancer risk. Thus, limiting time in sedentary behaviours may complement increasing level of moderate-vigorous physical activity as a means of reducing endometrial cancer risk. Taken together with the established biological plausibility of this relation, the totality of evidence now convincingly indicates that physical activity prevents or reduces risk of endometrial cancer.

Serum cytokine concentrations, flavonol intake and colorectal adenoma recurrence in the Polyp Prevention Trial.

BACKGROUND: Serum cytokine concentrations may reflect inflammatory processes occurring during the development of colorectal neoplasms. Flavonols, bioactive compounds found in plant-based foods and beverages, may inhibit colorectal neoplasms partly by attenuating inflammation. METHODS: Using logistic regression, we estimated odds ratios (ORs) and 95% confidence intervals (CIs) to investigate the association between serum concentrations of interleukin (IL) ß, 2, 8, 10, 12p70, granulocyte macrophage colony stimulating factor, interferon-γ, and tumour necrosis factor-α, measured over time, flavonol intake, estimated from a flavonol database used in conjunction with a food frequency questionnaire, and adenoma recurrence in 872 participants from the intervention arm of the Polyp Prevention Trial. RESULTS: Decreased IL-2 concentration during the trial increased the risk of any adenoma recurrence (4th vs 1st quartile, OR=1.68, 95% CI=1.13-2.49), whereas decreased IL-1ß or IL-10 reduced the risk of advanced adenoma recurrence (OR=0.37, 95% CI=0.15-0.94; OR=0.39, 95% CI=0.15-0.98, respectively). Individuals with flavonol intake above the median (29.7 mg per day) and decreased cytokine concentrations had the lowest risk of advanced adenoma recurrence. CONCLUSION: Overall, no consistent associations were observed between serum cytokine profile and colorectal adenoma recurrence; however, decreased cytokine concentrations during high flavonol consumption may indicate prevention of colorectal neoplasms.

Non-steroidal anti-inflammatory drugs and risk of gastric and oesophageal adenocarcinomas: results from a cohort study and a meta-analysis.

Use of aspirin or other non-steroidal anti-inflammatory drugs (NSAIDs) may reduce the risk of gastric or oesophageal adenocarcinomas. We examined the association between self-reported use of aspirin or non-aspirin NSAIDs in the earlier 12 months and gastric non-cardia (N=182), gastric cardia (N=178), and oesophageal adenocarcinomas (N=228) in a prospective cohort (N=311 115) followed for 7 years. Hazard ratios (HRs) and 95% confidence intervals (CIs) come from Cox models adjusted for potential confounders. Use of any aspirin (HR, 95% CI: 0.64, 0.47-0.86) or other NSAIDs (0.68, 0.51-0.92) was associated with a significantly lower risk of gastric non-cardia adenocarcinoma. Neither aspirin (0.86, 0.61-1.20) nor other NSAIDs (0.91, 0.67-1.22) had a significant association with gastric cardia cancer. We found no significant association between using aspirin (1.00, 0.73-1.37) or other NSAIDs (0.90, 69-1.17) and oesophageal adenocarcinoma. We also performed a meta-analysis of the association between the use of NSAIDs and risk of gastric and oesophageal adenocarcinoma. In this analysis, aspirin use was inversely associated with both gastric and oesophageal adenocarcinomas, with summary odds ratios (95% CI) for non-cardia, cardia, and oesophageal adenocarcinomas of 0.64 (0.52-0.80), 0.82 (0.65-1.04), and 0.64 (0.52-0.79), respectively. The corresponding numbers for other NSAIDs were 0.68 (0.57-0.81), 0.80 (0.67-0.95), and 0.65 (0.50-0.85), respectively.

Alcohol intake and risk of thyroid cancer in the NIH-AARP Diet and Health Study.

BACKGROUND: Certain studies suggest that alcohol may reduce the risk of thyroid cancer in women, but the effect in men remains unclear. METHODS: We analysed the association between alcohol and thyroid cancer in a large (n=490 159) prospective NIH-AARP Diet and Health Study with self-reported beer, wine, and liquor intakes. RESULTS: Over 7.5 years of follow-up (median), 170 men and 200 women developed thyroid cancer. Overall, the thyroid cancer risk decreased with greater alcohol consumption (> or =2 drinks per day vs none, relative risk=0.57, 95% CI 0.36-0.89, P-trend=0.01). CONCLUSIONS: These results suggest a potential protective role for alcohol consumption in thyroid cancer.

Index-based dietary patterns and risk of colorectal cancer: the NIH-AARP Diet and Health Study.

The authors compared how four indexes-the Healthy Eating Index-2005, Alternate Healthy Eating Index, Mediterranean Diet Score, and Recommended Food Score-are associated with colorectal cancer in the National Institutes of Health-AARP Diet and Health Study (n = 492,382). To calculate each score, they merged data from a 124-item food frequency questionnaire completed at study entry (1995-1996) with the MyPyramid Equivalents Database (version 1.0). Other variables included energy, nutrients, multivitamins, and alcohol. Models were stratified by sex and adjusted for age, ethnicity, education, body mass index, smoking, physical activity, and menopausal hormone therapy (in women). During 5 years of follow-up, 3,110 incident colorectal cancer cases were ascertained. Although the indexes differ in design, a similarly decreased risk of colorectal cancer was observed across all indexes for men when comparing the highest scores with the lowest: Healthy Eating Index-2005 (relative risk (RR) = 0.72, 95% confidence interval (CI): 0.62, 0.83); Alternate Healthy Eating Index (RR = 0.70, 95% CI: 0.61, 0.81); Mediterranean Diet Score (RR = 0.72, 95% CI: 0.63, 0.83); and Recommended Food Score (RR = 0.75, 95% CI: 0.65, 0.87). For women, a significantly decreased risk was found with the Healthy Eating Index-2005, although Alternate Healthy Eating Index results were similar. Index-based dietary patterns that are consistent with given dietary guidelines are associated with reduced risk.

Past body mass index and risk of mortality among women.

BACKGROUND: Epidemiologic studies of body mass index (BMI) in relation to mortality commonly exclude persons with health conditions and/or a history of smoking to prevent bias resulting from illness-related weight loss ('reverse causation'). Analysis of BMI from an earlier time period may minimize reverse causation without requiring exclusion of participants based on disease or smoking history. METHODS: We prospectively examined BMI based on technician measurements of weight and height from 10 years prior to start of follow-up in relation to subsequent mortality in a cohort of 50 186 women who were 40-93 years old at baseline in 1987-1989. Deaths were ascertained through the US National Death Index. Proportional hazards regression was used to estimate hazard ratios (HRs) of mortality, adjusted for age, education, race/ethnicity, income, menopausal hormone use, smoking and physical activity. RESULTS: During 10 years of follow-up through 1997, 5201 women died. Overall, we observed a J-shaped association between BMI and mortality, with increased risk for women who were underweight, overweight or obese. The HRs and 95% confidence intervals of mortality for BMI categories of <18.5, 18.5-20.9, 21.0-23.4 (reference), 23.5-24.9, 25.0-27.4, 27.5-29.9, 30.0-34.9 and 35.0+ kg m(-2) were 1.43 (1.19, 1.72), 1.07 (0.98, 1.17), 1.00 (reference), 1.10 (1.00, 1.20), 1.20 (1.11, 1.31), 1.23 (1.11, 1.37), 1.60 (1.44, 1.77) and 1.92 (1.64, 2.24). There was little evidence that pre-existing conditions (heart disease, diabetes and/or cancer) or smoking history modified the past BMI and mortality relation (P=0.54 and 0.76). CONCLUSIONS: In this large cohort of women, BMI based on technician measurements of weight and height from 10 years prior to baseline showed increased risk for mortality across the range of overweight and obesity, regardless of disease and smoking history. Observed associations between overweight, obesity and mortality in healthy individuals may also apply to persons with a history of disease or smoking.

The effects of a high-fruit and -vegetable, high-fiber, low-fat dietary intervention on serum concentrations of insulin, glucose, IGF-I and IGFBP-3.

OBJECTIVE: To determine the effects of dietary change on serum concentrations of insulin, glucose, IGF-I and IGFBP-3. SUBJECTS: From among participants in a randomized clinical trial of men and women without a history of diabetes who were 35 years old or older and who had at least one histologically confirmed colorectal adenoma removed during a qualifying colonoscopy within the 6 months before randomization, 750 subjects were selected for this analysis. METHODS: The authors analyzed fasting serum from 375 subjects with and 375 subjects without a recurrent polyp among participants in a randomized trial of a low-fat (20% of energy), high-fiber (18 g per 1000 kcals of energy intake) and high-fruit and -vegetable (5-8 servings per day) dietary intervention. RESULTS: After 4 years of follow-up, IGF-I concentration in the intervention group (N=248) declined by 8.86 ng/ml (initial mean of 133 ng/ml) and 7.74 ng/ml (initial mean value of 139 ng/ml) in the non-intervention group (N=502). Based on an unpaired t-test, these declines were both statistically significant, but the difference between groups for the decline in IGF-I (1.12 ng/ml ((95% confidence interval, -3.24 to 5.48)) was not. After 4 years, concentrations of IGFBP-3, insulin and glucose were not statistically different from values at baseline, and there were no differences in these serum measures between the intervention and control groups. In analysis restricted to lean (body mass index <25 kg/m(2)) subjects only, however, glucose concentrations in the intervention group decreased by 0.28 mmol/l, while they increased in the control group by 0.01 mmol/l (t-test for mean differences P=0.0003) over 4 years. CONCLUSIONS: A low-fat, high-fiber, high-fruit and -vegetable dietary intervention had minimal impact on serum concentrations of insulin, glucose, IGF-I and IGFBP-3 overall, but in lean subjects the intervention resulted in a significant reduction in serum glucose concentration.

What does it mean to be a cancer gene carrier? Problems in establishing causality from the molecular genetics of cancer.

This article addresses the following question: What does it mean to be a cancer gene carrier? The existence of families prone to cancer has prompted an intense search for predisposing heritable gene mutations. Genes that impart susceptibility to colorectal, breast, and ovarian cancers have been recently identified. It is doubtful, however, that the action of a single mutant gene totally accounts for the development of malignant disease. The mutant gene likely causes cancer in these family members only in conjunction with other genes, environmental factors, or both. Furthermore, although an individual carrier of a mutant gene within a cancer-prone family has an increased risk of malignancy, nutritional, pharmacologic, or other interventions may still confer protection. Extrapolations from cancer-prone families to the general population are even more problematic. The excess risk of malignancy among carriers of mutant genes who are not members of cancer-prone families is unknown. Large-scale epidemiologic studies are needed to determine the magnitude (or even the existence) of such excess risk.

Dietary fat, fat subtypes, and breast cancer in postmenopausal women: a prospective cohort study.

BACKGROUND: The intake of total dietary fat and of certain fat subtypes has been shown to be strongly associated with breast cancer in international comparisons and in animal experiments. However, observational epidemiologic studies have generally reported either weak positive or no associations. To extend the prospective epidemiologic evidence on this question, we examined the association between adult dietary intake of fat, fat subtypes, and breast cancer in a large, prospective cohort of postmenopausal women. METHODS: Participants were selected from a national breast cancer mammography screening program conducted from 1973 through 1981 at 29 centers throughout the United States. From 1987 through 1989, 40022 postmenopausal women satisfactorily completed a mailed, self-administered questionnaire that included a 60-item National Cancer Institute/Block food-frequency questionnaire. Women were then followed for an average of 5.3 years; 996 women developed breast cancer. Risk was assessed by use of Cox proportional hazard regression, with age as the underlying time metric. All statistical tests were two-sided. RESULTS: Compared with women in the lowest quintile (Q1) of percentage of energy from total fat, the adjusted risk ratio (RR) and 95% confidence interval (CI) for women in the highest quintile (Q5) was 1.07 (95% CI = 0.86-1.32). In analyses stratified by history of benign breast disease (BBD), a positive association was observed among only women with no history of BBD (RR (Q5 versus Q1) = 2.20; 95% CI = 1.41-3.42; test for trend, P =.0003). The increased risk in these women appeared to be attributable to unsaturated fat intake and oleic acid in particular. CONCLUSIONS: In this study, there was no overall association between fat intake during adulthood and breast cancer risk; however, among women with no history of BBD, there appeared to be a positive association between total and unsaturated fat intake and breast cancer risk.

Validation of intermediate end points in cancer research.

Investigations using intermediate end points as cancer surrogates are quicker, smaller, and less expensive than studies that use malignancy as the end point. We present a strategy for determining whether a given biomarker is a valid intermediate end point between an exposure and incidence of cancer. Candidate intermediate end points may be selected from case series, ecologic studies, and animal experiments. Prospective cohort and sometimes case-control studies may be used to quantify the intermediate end point-cancer association. The most appropriate measure of this association is the attributable proportion. The intermediate end point is a valid cancer surrogate if the attributable proportion is close to 1.0, but not if it is close to 0. Usually, the attributable proportion is close to neither 1.0 nor 0; in this case, valid surrogacy requires that the intermediate end point mediate an established exposure-cancer relation. This would in turn imply that the exposure effect would vanish if adjusted for the intermediate end point. We discuss the relative advantages of intervention and observational studies for the validation of intermediate end points. This validation strategy also may be applied to intermediate end points for adverse reproductive outcomes and chronic diseases other than cancer.

Effects of alcohol consumption on plasma and urinary hormone concentrations in premenopausal women.

BACKGROUND: Most epidemiologic studies of the relationship between alcohol consumption and breast cancer risk over the past decade have shown that persons who consume a moderate amount of alcohol are at 40%-100% greater risk of breast cancer than those who do not consume alcohol. Dose-response effects have been observed, but no causal relationship has been established. PURPOSE: This study examines the hypothesis that alcohol consumption affects levels of reproductive hormones. METHODS: A controlled-diet study lasting for six consecutive menstrual cycles was conducted. Participants were randomly assigned to two groups, and a crossover design was used. During the last three menstrual cycles, alcohol consumption of the two groups was reversed. Thirty-four premenopausal women, aged 21-40 years, with a history of regular menstrual cycles, consumed 30 g of ethanol (equivalent to approximately two average drinks) per day for three menstrual cycles and no alcohol for the other three. All food and alcohol consumed were provided by the study. Caloric intake was monitored to ensure that each woman would maintain body weight at approximately the baseline level. Hormone assays were performed on pooled plasma or 24-hour urine specimens collected during the follicular (days 5-7), peri-ovulatory (days 12-15), and mid-luteal (days 21-23) phases of the third menstrual cycle for subjects on each diet. RESULTS: Alcohol consumption was associated with statistically significant increases in levels of several hormones. Plasma dehydroepiandrosterone sulfate levels were 7.0% higher in the follicular phase (P = .05). In the peri-ovulatory phase, there were increases of 21.2% (P = .01) in plasma estrone levels, 27.5% (P = .01) in plasma estradiol levels, and 31.9% (P = .009) in urinary estradiol levels. In the luteal phase, urinary estrone levels rose 15.2% (P = .05), estradiol levels increased 21.6% (P = .02), and estriol levels rose 29.1% (P = .03). No changes were found in the percent of bioavailable estradiol, defined by the sum of percent free estradiol and percent albumin-bound estradiol. However, increased total estradiol levels in the peri-ovulatory phase suggest elevated absolute amounts of bioavailable estradiol. CONCLUSION: This study has shown increases in total estrogen levels and amount of bioavailable estrogens in association with alcohol consumption in premenopausal women. IMPLICATION: This possible explanatory mechanism for a positive association between alcohol consumption and breast cancer risk merits further investigation.

Risk factors for breast cancer in black women.

Risk factors for breast cancer were examined in black women in a hospital-based case-control study of 529 black women with breast cancer and 589 controls. Late age at menarche was associated with a reduced risk of breast cancer. Women having 5 or more children had a reduced risk relative to that of women with fewer or no children. Late age at first birth was associated with an elevated risk of breast cancer. Among postmenopausal black women, obesity [as measured by body mass index (BMI)] was associated with an increased risk; among premenopausal women, there was no association of breast cancer with BMI. Women whose menopause occurred at or after age 50 were at increased risk relative to those whose menopause occurred earlier. There was no association between number of years of education and breast cancer in black women. History of benign breast disease and history of breast cancer in mother or sisters both were risk factors. The risk factor profile for breast cancer in black women was similar to that observed in whites.

Dietary fat and breast cancer in the National Health and Nutrition Examination Survey I Epidemiologic Follow-up Study.

The relationship between dietary fat intake and breast cancer incidence was examined in the National Health and Nutrition Examination Survey I (NHANES I) Epidemiologic Follow-up Study cohort. This cohort is derived from adults (greater than or equal to 25 yr) examined in the NHANES I (1970-75) cross-sectional survey of the U.S. population and provides a mean follow-up time of 10 years. An analytic sample of 5,485 women, including 99 breast cancer cases (34 premenopausal and 65 postmenopausal at NHANES I baseline), was examined for associations with dietary intake of fat, percent energy from fat, total energy, saturated fat, polyunsaturated fat, monounsaturated fat, and cholesterol on the basis of a 24-hour recall administered at the baseline NHANES I examination. No significant differences in dietary fat intake between cases and noncases were evident when mean intakes for each group were compared. For total fat (g) and saturated fat (g), a significant inverse association was indicated in proportional hazards analyses. Adjustment of fat for total energy intake resulted in a smaller effect that was no longer statistically significant. Adjustment for accepted breast cancer risk factors did not change these findings. This prospective study of a sample from the U.S. population does not support the hypothesis that high dietary fat intake increases breast cancer risk. Indeed, some lower risk associated with high fat intake may be indicated, although this result may be influenced by methodologic problems with the dietary assessment.

Body fat distribution and breast cancer in the Framingham Study.

We examined the relation between central body fat distribution and breast cancer in a prospective cohort of women who participated in the Framingham Study. At the baseline examination in 1948, a total of 2,201 women aged 30-62 years were analyzed. An index of central to peripheral body fat (the central adiposity ratio) was calculated from the sum of the trunkal skinfolds (chest, subscapular, and abdominal) divided by the sum of the extremity skinfolds (triceps and thigh). These skinfolds were measured at the fourth examination in 1954. The cohort was followed for up to 28 years and yielded 106 cases of breast cancer. When divided into quartiles based on the central adiposity ratio, only women in the fourth quartile (those with the highest central to peripheral body fat distribution) demonstrated an increased risk for breast cancer. The age- and adiposity-adjusted relative risk estimate for having an increased central adiposity ratio (fourth quartile) compared to lower central adiposity ratios was 1.8 (95% confidence interval, 1.2-2.6). Adjustment for potential confounders of height, parity, and education did not appreciably alter this estimate (1.7, 1.1-2.5). There was no association between degree of adiposity, as measured by the sum of the five skinfolds or by body mass index (weight in kg divided by height in m2), and subsequent breast cancer. The results of this study suggest that increased central to peripheral body fat distribution predicts breast cancer risk independently of the degree of adiposity and may be a more specific marker of a premalignant hormonal pattern than degree of adiposity.

Is alcohol consumption related to breast cancer? Results from the Framingham Heart Study.

We studied the relation between alcohol consumption and breast cancer among women in the Framingham Heart Study cohort. A total of 2,636 women aged 31-64 years provided information on alcohol consumption at the second biennial examination. They were followed for up to 32 years; during this period, breast cancer was diagnosed in 143 of these women. Alcohol intake was also assessed at 10 and 20 years of follow-up and every 2 years thereafter. In analyses using only baseline alcohol intake, the multiple risk factor-adjusted relative risk (RR) estimate of breast cancer for any drinking, compared with nondrinking, was 0.8 [95% confidence interval (CI), 0.5-1.1]. For three levels of alcohol intake (0.1-1.4 g/day, 1.5-4.9 g/day, and greater than or equal to 5.0 g/day), the baseline analyses yielded RRs (vs. nondrinking) of 1.0 (CI, 0.6-1.5), 0.7 (CI, 0.4-1.1), and 0.6 (CI, 0.4-1.0), respectively. In analyses incorporating repeated measures of alcohol, the comparable RRs were 0.9 (CI, 0.6-1.2) for any drinking (vs. nondrinking) and 0.7 (CI, 0.4-1.4), 1.1 (CI, 0.7-1.8), and 0.8 (CI, 0.5-1.2), respectively, for the three levels of intake (vs. nondrinking). Alcohol consumption was not associated with an increased risk of breast cancer in this cohort.

Hormone replacement therapy and colorectal adenoma recurrence among women in the Polyp Prevention Trial.

BACKGROUND: Epidemiologic studies have suggested that estrogen may protect against the development of colorectal cancers and adenomatous polyps. We conducted a prospective study to evaluate the association between hormone replacement therapy (HRT) and adenoma recurrence among perimenopausal and postmenopausal women participating in the Polyp Prevention Trial, a randomized dietary intervention study of individuals with colorectal adenomas. METHODS: We used a questionnaire and interviews to collect detailed information, at baseline and at each of four annual study visits, from 620 women regarding hormone use, menopausal status, diet, alcohol consumption, and other risk factors. Adenoma recurrence was ascertained by complete colonoscopy at baseline and after 1 and 4 years. Logistic regression models were used to evaluate the association between hormone use and adenoma recurrence after adjusting for intervention group and for age and body mass index at baseline. All statistical tests were two-sided. RESULTS: Adenomas recurred in 200 women. There was no overall association between adenoma recurrence and either overall hormone use (odds ratio [OR] = 1.01; 95% confidence interval [CI] = 0.70 to 1.45), combined estrogen and progestin use (OR = 0.94; 95% CI = 0.57 to 1.56), or unopposed estrogen use (OR = 1.04; 95% CI = 0.68 to 1.59). HRT use was associated with a reduction in risk for recurrence of distal adenomas (OR = 0.56; 95% CI = 0.32 to 1.00) and a statistically nonsignificant increase in risk for recurrence of proximal adenomas (OR = 1.39; 95% CI = 0.85 to 2.26). We observed a statistically significant interaction between the HRT-adenoma recurrence association and age (P =.02). HRT was associated with a 40% reduced risk of adenoma recurrence among women older than 62 years (OR = 0.58; 95% CI = 0.35 to 0.97) but with an increased risk among women younger than 62 years (OR = 1.99; 95% CI = 1.11 to 3.55). CONCLUSIONS: HRT was not associated with a reduced risk for overall adenoma recurrence in this trial cohort, although there was a suggestion of an age interaction. The effect of age on the association needs to be confirmed in other adenoma recurrence trials.

Test reliability is critically important to molecular epidemiology: an example from studies of human papillomavirus infection and cervical neoplasia.

To demonstrate that it is critically important to achieve excellent test reliability before conducting full-scale molecular epidemiological studies, data were compared from two consecutive case-control studies of human papillomavirus (HPV) infection and cervical intraepithelial neoplasia. The major methodological difference between the two studies was the much greater reliability of the HPV test used in the second study. Although the first study used an assay considered state-of-the-art at that time, mediocre test reliability led to (a) a weakened association between HPV and risk of cervical intraepithelial neoplasia, (b) a weakened association between known risk factors for cervical intraepithelial neoplasia and HPV prevalence, (c) failure to demonstrate that HPV infection explains the known risk factors for cervical intraepithelial neoplasia, and (d) a marked reduction in the estimated proportion of cervical intraepithelial neoplasia attributable to HPV infection. With an improved assay, the second study strongly supported the idea that HPV infection is an intermediate end point explaining the known epidemiology of cervical intraepithelial neoplasia. Based on this experience and supportive theoretical considerations, we recommend that researchers optimize the reliability of innovative assays before application to full-scale molecular epidemiological projects.

Association of change in body mass with breast cancer.

We examined the relation between maximal adult change in body mass and breast cancer in the Epidemiological Follow-up Study of the first National Health and Nutrition Examination Survey. A total of 5599 women ages 25 to 74 years at the baseline examination in 1971 to 1975 were analyzed. Adult body mass change was calculated from baseline interview questions on lowest and highest adult weights, ages at those weights, and adult height. The cohort was followed for a median of 10 years and yielded 101 cases of breast cancer. In a multivariate model adjusting for potential confounders (age, body mass, education, parity, age at first birth, menopausal status, calorie and alcohol intake, and physical activity) the relative risk estimates for the upper two tertiles of body mass gain were 1.7 (95% confidence interval, 0.9 to 3.4) and 2.5 (95% confidence interval, 1.2 to 5.4), respectively, in comparison to the lowest tertile of adult body mass gain. The relative risk estimate for those with a loss in body mass during adulthood was 1.3 (95% confidence interval, 0.7 to 2.6) in comparison to those in the lowest tertile of adult body mass gain. There was no association between body mass at the baseline examination and subsequent breast cancer. The results of this study suggest that gain in adult body mass is a predictor of breast cancer risk independent of adult body mass. These results also suggest that avoidance of marked weight gain during adult life may reduce the risk of breast cancer.

Adult stature and risk of cancer.

We examined the relationship between adult stature and cancer incidence using data from the first U.S. National Health and Nutrition Examination Survey and its follow-up study. Among 12,554 participants 25-74 years old, 460 cancers occurred in men and 399 in women after an average follow-up period of approximately 10 years. The age-adjusted relative risk of cancer for the second (Q2) through fourth (Q4) quartiles of stature compared to the first quartile among men were significantly increased: 1.5, 1.4, and 1.4. After adjustment for race, cigarette smoking, income, and body mass index, the all-sites cancer relative risk increased slightly to 1.6, 1.5, and 1.6. For most cancer sites in men, and particularly colorectal cancer (relative risk = 2.1 for Q4), the lowest incidence was observed among those in the shortest quartile of stature. A weaker, positive association was evident among women, restricted primarily to cancer of the breast and colorectum (relative risk in Q4 = 2.1 and 1.6 for the two cancers, respectively). These findings indicate that short stature is associated with reduced risk of cancer, particularly in men, and suggest a role for nutrition early in life in human carcinogenesis.