Postpartum Breast Cancer and Survival in Women With Germline BRCA Pathogenic Variants.

Importance: In young-onset breast cancer (YOBC), a diagnosis within 5 to 10 years of childbirth is associated with increased mortality. Women with germline BRCA1/2 pathogenic variants (PVs) are more likely to be diagnosed with BC at younger ages, but the impact of childbirth on mortality is unknown. Objective: To determine whether time between most recent childbirth and BC diagnosis is associated with mortality among patients with YOBC and germline BRCA1/2 PVs. Design, Setting, and Participants: This prospective cohort study included women with germline BRCA1/2 PVs diagnosed with stage I to III BC at age 45 years or younger between 1950 and 2021 in the United Kingdom, who were followed up until November 2021. Data were analyzed from December 3, 2021, to November 29, 2023. Exposure: Time between most recent childbirth and subsequent BC diagnosis, with recent childbirth defined as 0 to less than 10 years, further delineated to 0 to less than 5 years and 5 to less than 10 years. Main Outcomes and Measures: The primary outcome was all-cause mortality, censored at 20 years after YOBC diagnosis. Mortality of nulliparous women was compared with the recent post partum groups and the 10 or more years post partum group. Cox proportional hazards regression analyses were adjusted for age, tumor stage, and further stratified by tumor estrogen receptor (ER) and BRCA gene status. Results: Among 903 women with BRCA PVs (mean [SD] age at diagnosis, 34.7 [6.1] years; mean [SD] follow-up, 10.8 [9.8] years), 419 received a BC diagnosis 0 to less than 10 years after childbirth, including 228 women diagnosed less than 5 years after childbirth and 191 women diagnosed 5 to less than 10 years after childbirth. Increased all-cause mortality was observed in women diagnosed within 5 to less than 10 years post partum (hazard ratio [HR], 1.56 [95% CI, 1.05-2.30]) compared with nulliparous women and women diagnosed 10 or more years after childbirth, suggesting a transient duration of postpartum risk. Risk of mortality was greater for women with ER-positive BC in the less than 5 years post partum group (HR, 2.35 [95% CI, 1.02-5.42]) and ER-negative BC in the 5 to less than 10 years post partum group (HR, 3.12 [95% CI, 1.22-7.97]) compared with the nulliparous group. Delineated by BRCA1 or BRCA2, mortality in the 5 to less than 10 years post partum group was significantly increased, but only for BRCA1 carriers (HR, 2.03 [95% CI, 1.15-3.58]). Conclusions and Relevance: These findings suggest that YOBC with germline BRCA PVs was associated with increased risk for all-cause mortality if diagnosed within 10 years after last childbirth, with risk highest for ER-positive BC diagnosed less than 5 years post partum, and for ER-negative BC diagnosed 5 to less than 10 years post partum. BRCA1 carriers were at highest risk for poor prognosis when diagnosed at 5 to less than 10 years post partum. No such associations were observed for BRCA2 carriers. These results should inform genetic counseling, prevention, and treatment strategies for BRCA PV carriers.

Lifetime alcohol consumption patterns and young-onset breast cancer by subtype among Non-Hispanic Black and White women in the Young Women's Health History Study.

PURPOSE: The role of alcohol in young-onset breast cancer (YOBC) is unclear. We examined associations between lifetime alcohol consumption and YOBC in the Young Women's Health History Study, a population-based case-control study of breast cancer among Non-Hispanic Black and White women < 50 years of age. METHODS: Breast cancer cases (n = 1,812) were diagnosed in the Metropolitan Detroit and Los Angeles County SEER registry areas, 2010-2015. Controls (n = 1,381) were identified through area-based sampling and were frequency-matched to cases by age, site, and race. Alcohol consumption and covariates were collected from in-person interviews. Weighted multivariable logistic regression was conducted to calculate adjusted odds ratios (aOR) and 95% confidence intervals (CI) for associations between alcohol consumption and YOBC overall and by subtype (Luminal A, Luminal B, HER2, or triple negative). RESULTS: Lifetime alcohol consumption was not associated with YOBC overall or with subtypes (all ptrend ≥ 0.13). Similarly, alcohol consumption in adolescence, young and middle adulthood was not associated with YOBC (all ptrend ≥ 0.09). An inverse association with triple-negative YOBC, however, was observed for younger age at alcohol use initiation (< 18 years vs. no consumption), aOR (95% CI) = 0.62 (0.42, 0.93). No evidence of statistical interaction by race or household poverty was observed. CONCLUSIONS: Our findings suggest alcohol consumption has a different association with YOBC than postmenopausal breast cancer-lifetime consumption was not linked to increased risk and younger age at alcohol use initiation was associated with a decreased risk of triple-negative YOBC. Future studies on alcohol consumption in YOBC subtypes are warranted.

Lifetime personal cigarette smoking and risk of young-onset breast cancer by subtype among non-Hispanic Black and White women in the Young Women's Health History Study.

PURPOSE: To evaluate the association between lifetime personal cigarette smoking and young-onset breast cancer (YOBC; diagnosed <50 years of age) risk overall and by breast cancer (BC) subtype, and whether risk varies by race or socioeconomic position (SEP). METHODS: Data are from the Young Women's Health History Study (YWHHS), a population-based case-control study of non-Hispanic Black (NHB) and White (NHW) women, ages 20-49 years (n = 1812 cases, n = 1381 controls) in the Los Angeles County and Metropolitan Detroit Surveillance, Epidemiology, and End Results (SEER) registry areas, 2010-2015. Lifetime personal cigarette smoking characteristics and YOBC risk by subtype were examined using sample-weighted, multivariable-adjusted polytomous logistic regression. RESULTS: YOBC risk associated with ever versus never smoking differed by subtype (Pheterogeneity = 0.01) with risk significantly increased for Luminal A (adjusted odds ratio [aOR] 1.34; 95% confidence interval [CI] 1.06-1.68) and HER2-type (aOR 1.97; 95% CI 1.23-3.16), and no association with Luminal B or Triple Negative subtypes. Additionally, ≥30 years since smoking initiation (versus never) was statistically significantly associated with an increased risk of Luminal A (aOR 1.55; 95% CI 1.07-2.26) and HER2-type YOBC (aOR 2.77; 95% CI 1.32-5.79), but not other subtypes. In addition, among parous women, smoking initiated before first full-term pregnancy (versus never) was significantly associated with an increased risk of Luminal A YOBC (aOR 1.45; 95% CI 1.11-1.89). We observed little evidence for interactions by race and SEP. CONCLUSION: Findings confirm prior reports of a positive association between cigarette smoking and Luminal A YOBC and identify a novel association between smoking and HER2-type YOBC.

Body Mass Index Is Inversely Associated with Risk of Postmenopausal Interval Breast Cancer: Results from the Women's Health Initiative.

Interval breast cancer refers to cancer diagnosed after a negative screening mammogram and before the next scheduled screening mammogram. Interval breast cancer has worse prognosis than screening-detected cancer. Body mass index (BMI) influences the accuracy of mammography and overall postmenopausal breast cancer risk, yet how is obesity associated with postmenopausal interval breast cancer incidence is unclear. The current study included cancer-free postmenopausal women aged 50-79 years at enrollment in the Women's Health Initiative who were diagnosed with breast cancer during follow-up. Analyses include 324 interval breast cancer cases diagnosed within one year after the participant's last negative screening mammogram and 1969 screening-detected breast cancer patients. Obesity (BMI ≥ 30 kg/m2) was measured at baseline. Associations between obesity and incidence of interval cancer were determined by sequential logistic regression analyses. In multivariable-adjusted models, obesity was inversely associated with interval breast cancer risk [OR (95% CI) = 0.65 (0.46, 0.92)]. The inverse association persisted after excluding women diagnosed within 2 years [OR (95% CI) = 0.60 (0.42, 0.87)] or 4 years [OR (95% CI) = 0.56 (0.37, 0.86)] of enrollment, suggesting consistency of the association regardless of screening practices prior to trial entry. These findings warrant confirmation in studies with body composition measures.

Diet-Driven Inflammation and Insulinemia and Risk of Interval Breast Cancer.

Interval breast cancers (IBCs) emerge after a non-suspicious mammogram and before the patient's next scheduled screen. Risk factors associated with IBC have not been identified. This study evaluated if the empirical dietary inflammatory pattern (EDIP) or empirical dietary index for hyperinsulinemia (EDIH) scores are associated with IBC compared to screen-detected breast cancer. Data were from women 50-79 years-old in the Women's Health Initiative cohort who completed food frequency questionnaires at baseline (1993-98) and were followed through March 31, 2019 for breast cancer detection. Women were identified as having either IBC diagnosed within 1-year after their last negative screening mammogram (N = 317) or screen-detected breast cancer (N = 1,928). Multivariable-adjusted logistic regression analyses were used to estimate odds ratios for risk of IBC compared to screen-detected cancer in dietary index tertiles. No associations were observed between EDIP or EDIH and IBC. Odds ratios comparing the highest to the lowest dietary index tertile were 1.08; 95%CI, 0.78-1.48 for EDIP and 0.92; 95%CI, 0.67-1.27 for EDIH. The null associations persisted when stratified by BMI categories. Findings suggest that diet-driven inflammation or insulinemia may not be substantially associated with IBC risk among postmenopausal women. Future studies are warranted to identify modifiable factors for IBC prevention.

Theory, methods, and operational results of the Young Women's Health History Study: a study of young-onset breast cancer incidence in Black and White women.

PURPOSE: The etiology of young-onset breast cancer (BC) is poorly understood, despite its greater likelihood of being hormone receptor-negative with a worse prognosis and persistent racial and socioeconomic inequities. We conducted a population-based case-control study of BC among young Black and White women and here discuss the theory that informed our study, exposures collected, study methods, and operational results. METHODS: Cases were non-Hispanic Black (NHB) and White (NHW) women age 20-49 years with invasive BC in metropolitan Detroit and Los Angeles County SEER registries 2010-2015. Controls were identified through area-based sampling from the U.S. census and frequency matched to cases on study site, race, and age. An eco-social theory of health informed life-course exposures collected from in-person interviews, including socioeconomic, reproductive, and energy balance factors. Measured anthropometry, blood (or saliva), and among cases SEER tumor characteristics and tumor tissue (from a subset of cases) were also collected. RESULTS: Of 5,309 identified potentially eligible cases, 2,720 sampled participants were screened and 1,812 completed interviews (682 NHB, 1140 NHW; response rate (RR): 60%). Of 24,612 sampled control households 18,612 were rostered, 2,716 participants were sampled and screened, and 1,381 completed interviews (665 NHB, 716 NHW; RR: 53%). Ninety-nine% of participants completed the main interview, 82% provided blood or saliva (75% blood only), and SEER tumor characteristics (including ER, PR and HER2 status) were obtained from 96% of cases. CONCLUSIONS: Results from the successfully established YWHHS should expand our understanding of young-onset BC etiology overall and by tumor type and identify sources of racial and socioeconomic inequities in BC.

Effects of changes in lunch-time competitive foods, nutrition practices, and nutrition policies on low-income middle-school children's diets.

BACKGROUND: The School Nutrition Advances Kids project tested the effectiveness of school-initiated and state-recommended school nutrition practice and policy changes on student dietary intake in low-income middle schools. METHODS: Schools recruited by an application for grant funding were randomly assigned to (1) complete an assessment of nutrition education, policies, and environments using the Healthy School Action Tools (HSAT) and implement an action plan, (2) complete the HSAT, implement an action plan, and convene a student nutrition action team, (3) complete the HSAT and implement an action plan and a Michigan State Board of Education nutrition policy in their cafeteria à la carte, or (4) a control group. All intervention schools were provided with funding and assistance to make self-selected nutrition practice, policy, or education changes. Block Youth Food Frequency Questionnaires were completed by 1176 seventh-grade students from 55 schools at baseline and during eighth-grade follow-up. Nutrient density and food group changes for the intervention groups were compared to the control group, controlling for baseline dietary intake values, gender, race/ethnicity, school kitchen type, urbanization, and percent of students eligible for free or reduced-price meals. Analyses were conducted by randomization and based on changes the schools self-selected. RESULTS: Improvements in students' nutrient density and food group intake were found when schools implemented at least three new nutrition practice changes and established at least three new nutrition policies. Students in schools that introduced mostly healthful foods in competitive venues at lunch demonstrated the most dietary improvements. CONCLUSIONS: New USDA nutrition standards for à la carte and vending will likely increase the healthfulness of middle school children's diets.

A population-based case-control study of fetal growth, gestational age, and maternal breast cancer.

Fetal growth or gestational age in a woman's pregnancies may modify pregnancy-related breast cancer risk, yet studies of these exposures are few. The authors conducted a population-based case-control study among parous Michigan women aged ≤50 years using linked Michigan Cancer Registry (1985-2004) and Michigan livebirth records (1978-2004). Breast cancer cases (n = 7,591) were matched 1:4 to controls (n = 28,382) on maternal birth year and race. Using conditional logistic regression, the authors examined the associations of gestational age (in weeks) and fetal growth (defined using birth weight percentiles for gestational age) in first and last births with breast cancer risk. Having a small-for-gestational-age or large-for-gestational-age infant at a maternal first or last birth was not associated with breast cancer risk, but having a small-for-gestational-age infant at a last birth at ≥30 years modestly reduced risk: odds ratio = 0.82 (95% confidence interval: 0.68, 0.98). First delivery at <32 or >41 weeks also modestly reduced risk: odds ratio = 0.80 (95% confidence interval: 0.62, 1.04) or 0.92 (95% confidence interval: 0.85, 0.99), respectively. In the largest case-control study to date, fetal growth was not associated with overall breast cancer risk in women aged ≤50, and there was some evidence for reduced breast cancer risk for early or late gestational age in first births only.

Polymorphisms in the adenomatous polyposis coli (APC) gene and advanced colorectal adenoma risk.

While germline mutations in the adenomatous polyposis coli (APC) gene cause the hereditary colon cancer syndrome (familial adenomatous polyposis (FAP)), the role of common germline APC variants in sporadic adenomatous polyposis remains unclear. We studied the association of eight APC single nucleotide polymorphisms (SNPs), possibly associated with functional consequences, and previously identified gene-environment (dietary fat intake and hormone replacement therapy (HRT) use) interactions, in relation to advanced colorectal adenoma in 758 cases and 767 sex- and race-matched controls, randomly selected from the screening arm of the Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial. Cases had at least one verified advanced adenoma of the distal colon; controls, a negative sigmoidoscopy. We did not observe an association between genotypes for any of the eight APC SNPs and advanced distal adenoma risk (P(global gene-based)=0.92). Frequencies of identified common haplotypes did not differ between cases and controls (P(global haplotype test)=0.97). However, the risk for advanced distal adenoma was threefold higher for one rare haplotype (cases: 2.7%; controls: 1.6%) (odds ratio (OR)=3.27; 95% confidence interval (CI)=1.08-9.88). The genetic association between D1822V and advanced distal adenoma was confined to persons consuming a high-fat diet (P(interaction)=0.03). Similar interactions were not observed with HRT use. In our large, nested case-control study of advanced distal adenoma and clinically verified adenoma-free controls, we observed no association between specific APC SNPs and advanced adenoma. Fat intake modified the APC D1822V-adenoma association, but further studies are warranted.

Pregnancy characteristics and maternal breast cancer risk: a review of the epidemiologic literature.

The short- and long-term effects of pregnancy on breast cancer risk are well documented. Insight into potential biological mechanisms for these associations may be gained by studying breast cancer risk and pregnancy characteristics (e.g., preeclampsia, twining), which may reflect hormone levels during pregnancy. To date, no review has synthesized the published literature for pregnancy characteristics and maternal breast cancer using systematic search methods. We conducted a systematic search to identify all published studies. Using PUBMED (to 31 July 2009), 42 relevant articles were identified. Several studies suggest that multiple births may be associated with a lowered breast cancer risk of about 10-30%, but results were inconsistent across 18 studies. The majority of 13 studies suggest about a 20-30% reduction in risk with preeclampsia and/or gestational hypertension. Six of seven studies reported no association for infant sex and breast cancer risk. Data are sparse and conflicting for other pregnancy characteristics such as gestational age, fetal growth, pregnancy weight gain, gestational diabetes, and placental abnormalities. The most consistent findings in a generally sparse literature are that multiple births and preeclampsia may modestly reduce breast cancer risk. Additional research is needed to elucidate associations between pregnancy characteristics, related hormonal profiles, and breast cancer risk.

Dietary predictors of the insulin-like growth factor system in adolescent females: results from the Dietary Intervention Study in Children (DISC).

BACKGROUND: The insulin-like growth factor (IGF) system is associated with the adult diet and chronic disease. Childhood diet may influence chronic disease through its effect on the IGF system; however, there is limited information describing the dietary predictors of the IGF system in adolescents. OBJECTIVE: We examined associations between dietary food intake [fat, protein (animal and vegetable), carbohydrate, lactose, dietary fiber, calcium, zinc, and sodium] and serum IGF-I, IGF binding protein 1 (IGFBP-1), IGF binding protein 3 (IGFBP-3), and the IGF-I:IGFBP-3 molar ratio in adolescent females. DESIGN: One hundred fifty-nine adolescent females in the Dietary Intervention Study in Children (age range: 14-18 y; 0.2-6.3 y postmenarche) were included. The dietary intake was assessed via three 24-h dietary recalls. IGF-related biomarkers were determined by using radioimmunoassays. Associations between dietary intakes and biomarkers were assessed with Pearson's correlations and multivariable linear regression. Dietary intakes and biomarkers were logarithmically transformed; thus, beta coefficients represented percentages. RESULTS: In analyses adjusted for energy, age, and time since menarche, significant correlations (P < 0.05) were as follows: IGF-I with total protein, lactose, calcium, and sodium; IGFBP-3 with total fat (inverse), lactose, fiber, and calcium; IGF-I/IGFBP-3 with lactose and calcium; and IGFBP-1 with vegetable protein. In multivariable analyses, significant predictors of IGF-I were energy (beta = 0.14, P < 0.05) and calcium (beta = 0.14, P < 0.01), the significant predictor of IGFBP-3 was calcium (beta = 0.07, P < 0.05), and significant predictors of IGFBP-1 were vegetable protein (beta = 0.49, P < 0.05) and body mass index-for-age percentile (beta = -0.01, P < 0.001). CONCLUSION: This study provides evidence that dietary intake affects IGF-related biomarkers-particularly elevated calcium with IGF-I and IGFBP-3 and elevated vegetable protein with IGFBP-1-and, to our knowledge, is novel in reporting these associations in adolescent females. The Dietary Intervention Study in Children was registered at clinicaltrials.gov as NCT00000459.

Understanding the increased risk of neural tube defect-affected pregnancies among Mexico-born women in California: immigration and anthropometric factors.

Mexico-born women in the United States have an unexplained twofold increased risk of neural tube defect (NTD)-affected pregnancies. We examined whether immigration characteristics were associated with the NTD risk and whether anthropometric factors contributed to the increased risk among Mexico-born women. Data were derived from a large population-based case-control study in California. In-person interviews were conducted with mothers of 538 (88% of eligible) NTD-affected fetuses/infants and mothers of 539 (88%) randomly selected non-malformed control infants. The crude odds ratio (OR) for NTDs among all Mexico-born women, women residing <2 years in the US, and women >16 years old at immigration compared with non-Hispanic white women was 2.4 [95% confidence interval (CI) = 1.8, 3.3], 7.2 [95% CI = 3.7, 14.0] and 3.0 [95% CI = 2.0, 4.4], respectively. Risk for second- or third-generation Mexican-Americans was similar to that of white women. The crude OR for all Mexico-born women was reduced from 2.4 to 2.0 [95% CI = 1.3, 3.0] and for those residing <2 years in the US from 8.4 to 7.1 [95% CI = 3.2, 15.3] after adjustment for maternal body mass index (BMI), height, compromised diet, diabetes, and other known risk factors. In term pregnancies, additional adjustment for pregnancy weight gain reduced the OR in all Mexico-born women and recent immigrants by 16% and 25%, respectively. Low pregnancy weight gain (<10 vs. 10-14 kg) was particularly associated with increased NTD risk among Mexico-born women (OR(ADJ) = 5.8; 95% CI = 2.1, 15.8). Findings indicate that recent Mexican immigrants have a sevenfold increased risk for NTDs. Maternal BMI and height contributed very little, and inadequate weight gain contributed modestly to the NTD risk disparity for Mexican immigrants.

Dietary sources of nutrients among rural Native American and white children.

OBJECTIVE: To identify important food sources of energy, fiber, and major macro- and micronutrients among rural Native American and white children. DESIGN: In a 1997 cross-sectional study, food frequency questionnaire data were collected during in-person interviews with caregivers of young children. SUBJECTS/SETTING: Participants included a representative sample of 329 rural Native American and non-Hispanic white children aged 1 through 6 years living in northeastern Oklahoma. STATISTICAL ANALYSES: The percentage that each of 85 food items contributed to the population intake of 10 dietary constituents was calculated for the total sample and by age and race/ethnicity. Percentages are presented in descending rank order for foods providing at least 2% of the total sample intake. Z scores were used to assess age and racial/ethnic differences in food sources. RESULTS: Primary energy sources among study children were milk, cheese, white breads, salty snacks, nondiet soft drinks, hot dogs, candy, and sweetened fruit drinks. Diets showed poor food variety. With few exceptions (eg, milk, cheese, 100% orange juice, ready-to-eat cereals, peanuts/peanut butter, and dried beans), top sources of most dietary constituents were low-nutrient-dense high-fat foods and refined carbohydrates. Solid fruits and vegetables contributed minimally to nutrient and fiber intake. There were few differences in food sources by age or race/ethnicity. CONCLUSIONS: Among rural Native American and white children in northeastern Oklahoma, food sources of nutrients appear less healthful than found in national samples. Sugar-sweetened beverages, high-fat foods, and refined carbohydrates are displacing more nutrient-dense alternatives, increasing children's risk for childhood obesity, type 2 diabetes, and adult chronic disease.

Empirically derived dietary patterns and risk of postmenopausal breast cancer in a large prospective cohort study.

BACKGROUND: Inconsistent associations have been reported between diet and breast cancer. OBJECTIVE: We prospectively examined the association between dietary patterns and postmenopausal breast cancer risk in a US-wide cohort study. DESIGN: Data were analyzed from 40 559 women who completed a self-administered 61-item Block food-frequency questionnaire in the Breast Cancer Detection Demonstration Project, 1987-1998; 1868 of those women developed breast cancer. Dietary patterns were defined by using principal components factor analysis. Cox proportional hazard regression was used to assess breast cancer risk. RESULTS: Three major dietary patterns emerged: vegetable-fish/poultry-fruit, beef/pork-starch, and traditional southern. The vegetable-fish/poultry-fruit pattern was associated with higher education than were the other patterns, but was similar in nutrient intake to the traditional southern pattern. After adjustment for confounders, there was no significant association between the vegetable-fish/poultry-fruit and beef/pork-starch patterns and breast cancer. The traditional southern pattern, however, was associated with a nonsignificantly reduced breast cancer risk among all cases (in situ and invasive) that was significant for invasive breast cancer (relative hazard = 0.78; 95% CI = 0.65, 0.95; P for trend = 0.003). This diet was also associated with a reduced risk in women without a family history of breast cancer (P = 0.05), who were underweight or normal weight [body mass index (in kg/m(2)) < 25; P = 0.02], or who had tumors positive for estrogen receptor (P = 0.01) or progesterone receptor (P = 0.003). Foods in the traditional southern pattern associated with reduced breast cancer risk were legumes, low mayonnaise-salad dressing intake, and possibly cabbage. CONCLUSIONS: The traditional southern diet or its components are associated with a reduced risk of invasive breast cancer in postmenopausal women.

Lifetime reproductive and anthropometric risk factors for breast cancer in postmenopausal women.

Hormonally-linked adult reproductive and anthropometric risk factors have been well established in the etiology of postmenopausal breast cancer, though early life exposures have been evaluated only more recently. Here, we examine the evidence for associations between lifetime reproductive and anthropometric risk factors for postmenopausal breast cancer. The review finds some evidence for the hypothesis that breast cancer risk is determined by the number of susceptible stem cells, modified by the hormonal environment. The in utero experience of an infant may be associated with postmenopausal breast cancer; preeclampsia may decrease and greater birthweight increase risk, but more evidence is needed. Earlier and more rapid childhood growth appears to increase postmenopausal breast cancer risk and childhood obesity to decrease risk, but very few studies have yet examined these associations. Increased final height and earlier age at menarche are consistently associated with increased risk for postmenopausal breast cancer. Later age at first birth, decreased parity, later menopausal age, use of hormone replacement therapy (especially progestin containing), and increased postmenopausal adiposity are well-established risk factors for postmenopausal breast cancer. The effect of a woman's own pregnancy conditions and lactation are not established. Further investigation is needed to identify whether events occurring early in life modify later events or accumulate over the life course. Many aspects of this research can be conducted by examining the influence of early life events on intermediary events without the need for longitudinal data.

Meat, fat, and their subtypes as risk factors for colorectal cancer in a prospective cohort of women.

The authors investigated the association of intakes of meat and fat with colorectal cancer in a prospective cohort of women in the United States. Between 1987 and 1989, 45,496 women completed a 62-item National Cancer Institute/Block food frequency questionnaire, and during 386,716 person-years of follow-up, there were 487 incident cases of colorectal cancer. The authors used Cox proportional hazards regression to estimate relative risks and 95% confidence intervals for total meat, red meat, white meat, processed meat, and well-done meat intakes, as well as for total fat, saturated fat, and unsaturated fat. Relative risks for increasing quintiles of total meat and red meat consumption indicated no association with colorectal cancer (relative risk for high compared with low quintile = 1.10, 95% confidence interval: 0.83, 1.45) for red meat. For total fat, there was also no association with increasing quintiles of consumption (relative risk for high compared with low quintile = 1.14, 95% confidence interval: 0.86, 1.53). Additionally, none of the other subtypes of either meat or fat showed any association with colorectal cancer. This study provided no evidence of an association between either meat or fat (or any of their subtypes) and colorectal cancer incidence, but the authors cannot rule out the possibility of a modest association.

Fruit and vegetable intakes and the risk of colorectal cancer in the Breast Cancer Detection Demonstration Project follow-up cohort.

BACKGROUND: Recent findings have cast doubt on the hypothesis that high intakes of fruit and vegetables are associated with a reduced risk of colorectal cancer. OBJECTIVE: In a large prospective cohort of women, we examined the association between fruit and vegetable intakes and colorectal cancer. DESIGN: Between 1987 and 1989, 45490 women with no history of colorectal cancer satisfactorily completed a 62-item Block-National Cancer Institute food-frequency questionnaire. During 386142 person-years of follow-up, 314 women reported incident colorectal cancer, searches of the National Death Index identified an additional 106 colorectal cancers, and a match with state registries identified another 65 colorectal cancers for a total of 485 cases. We used Cox proportional hazards regression analysis to estimate the relative risks (RRs) and 95% CIs in both energy-adjusted and fully adjusted models. RESULTS: In models using the multivariate nutrient-density model of energy adjustment, RRs for increasing quintile of fruit consumption indicated no significant association with colorectal cancer [RR (95% CI)]: 1.00 (reference), 0.94 (0.70, 1.26), 0.85 (0.63, 1.15), 1.07 (0.81, 1.42), and 1.09 (0.82, 1.44). For vegetable consumption, there was also no significant association in the multivariate nutrient-density model with increasing quintiles of consumption: 1.00 (reference), 0.77 (0.58, 1.02), 0.83 (0.63, 1.10), 0.90 (0.69, 1.19), and 0.92 (0.70, 1.22). Additionally, 3 alternative models of energy adjustment showed no significant association between increases in vegetable intake and the risk of colorectal cancer. CONCLUSION: Although the limitations of our study design and data merit consideration, this investigation provides little evidence of an association between fruit and vegetable intakes and colorectal cancer.