The Nurses' Health Study has grown from a simple questionnaire-based study initiated in 1976 to a rich resource of information collected over 29 years. Important details about lifestyle have been collected throughout the study and, as the study has progressed, blood samples and DNA from buccal cells have been collected and stored. Tumour samples have also been collected from participants who developed cancer. Through analyses that integrate information from these various sources we are advancing our understanding of the causes of cancer and the potential for prevention.
The Nurses' Health Study is the first large prospective cohort study of women with updated exposure assessment for a broad range of lifestyle factors, endogenous hormones and DNA, in relation to risk of cancer.
The Nurses' Health Study can assess overall risks and benefits of lifestyle factors by evaluating them in relation to a range of cancers and other chronic conditions, and in terms of total mortality.
Using diet data, which was first collected in 1980, we showed that alcohol intake is related to an increased risk of breast cancer independent of other dietary factors. Adult dietary-fat intake was not related to increased breast cancer risk in this and subsequent prospective studies.
The long-term use of multivitamins containing folate is associated with a reduced risk of colon cancer. This association was confirmed by findings from several studies, including the discovery that a functional polymorphism in the methylene-tetrahydrofolate reductase gene was associated with increased colon cancer risk and that plasma levels of folate were inversely related to colon cancer risk.
Both oestrogen and testosterone levels in postmenopausal women are related to an increased risk of breast cancer. Because of this, plasma oestrogen and testosterone levels are now being added to risk-prediction models for breast cancer.
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Doll, R. & Peto, R. Mortality in relation to smoking: 20 years' observations on male British doctors. BMJ 2, 1525–1536 (1976).
Vessey, M. P., Doll, R. & Jones, K. Oral contraceptives and breast cancer. Progress report of an epidemiological study. Lancet 1, 941–943 (1975).
American Nurses' Association. National Sample Survey of Registered Nurses. A report on the nurse population and factors affecting their supply (Public Health Service, Hyattsville, 1977).
Stampfer, M. J. et al. Test of the National Death Index. Am. J. Epidemiol. 119, 837–839 (1984).
London, S. T., Connolly, J. L., Schnitt, S. J. & Colditz, G. A. A prospective study of benign breast disease and the risk of breast cancer. J. Am. Med. Assoc. 267, 941–944 (1992).
Jacobs, T. W., Byrne, C., Colditz, G., Connolly, J. L. & Schnitt, S. J. Radial scars in benign breast biopsy specimens and breast cancer risk: a case–control study. N. Engl. J. Med. 340, 430–436 (1999).
Holmes, M. D. et al. Dietary factors and the survival of women with breast carcinoma. Cancer 86, 826–835 (1999).
Kroenke, C. H., Chen, W. Y., Rosner, B. & Holmes, M. D. Weight, weight gain, and survival after breast cancer diagnosis. J. Clin. Oncol. 23, 1370–1378 (2005).
Hunter, D. J. et al. A prospective study of NAT2 acetylation genotype, cigarette smoking, and risk of breast cancer. Carcinogenesis 18, 2127–2132 (1997).
Chen, J. et al. A methylenetetrahydrofolate reductase polymorphism and the risk of colorectal cancer. Cancer Res. 56, 4862–4864 (1996).
Colditz, G. A. The Nurses' Health Study: a cohort of US women followed since 1976. J. Am. Med. Womens Assoc. 50, 40–44 (1995).
Colditz, G. A., Manson, J. E. & Hankinson, S. E. The Nurses' Health Study: 20-year contribution to the understanding of health among women. J. Womens Health 6, 49–62 (1997).
Willett, W. & Colditz, G. Approaches to conducting large cohort studies. Epidemiol. Rev. 20, 91–99 (1999).
Romieu, I. et al. A prospective study of oral contraceptive use and the risk of breast cancer in women. J. Natl Cancer Inst. 81, 1313–1321 (1989).
Collaborative Group on Hormonal Factors in Breast Cancer. Breast cancer and hormonal contraceptives: collaborative reanalysis of individual data on 53,297 women with breast cancer and 100,239 women without breast cancer from 54 epidemiological studies. Lancet 347, 1713–1727 (1996).
Hankinson, S. et al. A quantitative assessment of oral contraceptive use and risk of ovarian cancer. Obstet. Gynecol. 80, 708–714 (1992).
Martinez, M. E. et al. Leisure-time physical activity, body size, and colon cancer in women. Nurses' Health Study Research Group. J. Natl Cancer Inst. 89, 948–955 (1997). Shows that the association of physical activity and obesity with colon cancer in women is comparable to that seen in men.
Colditz, G. A. Oral contraceptive use and mortality during twelve years of follow-up: the Nurses Health Study. Ann. Intern. Med. 120, 821–826 (1994).
Willett, W. C. et al. Moderate alcohol consumption and the risk of breast cancer. N. Engl. J. Med. 316, 1174–1180 (1987). The first prospective study to document the relationship between moderate alcohol consumption and risk of breast cancer after excluding other possible dietary causes of breast cancer.
Cho, E. et al. Alcohol intake and colorectal cancer: a pooled analysis of 8 cohort studies. Ann. Intern. Med. 140, 603–613 (2004).
Giovannucci, E. et al. Multivitamin use, folate, and colon cancer in women in the Nurses' Health Study. Ann. Intern. Med. 129, 517–524 (1998). Repeated assessment of the use of multivitamins allows duration of use to be evaluated in relation to colon cancer risk. This study shows a strong trend of lower risk with longer duration of use.
Giovannucci, E. Alcohol, one-carbon metabolism, and colorectal cancer: recent insights from molecular studies. J. Nutr. 134, S2475–S2481 (2004).
Zhang, S. et al. A prospective study of folate intake and the risk of breast cancer. JAMA 281, 1632–1637 (1999).
Zhang, S. M. et al. Plasma folate, vitamin B6, vitamin B12, homocysteine, and risk of breast cancer. J. Natl Cancer Inst. 95, 373–380 (2003).
Willett, W. C. et al. Dietary fat and the risk of breast cancer. N. Engl. J. Med. 316, 22–28 (1987). Shows no overall association between fat intake and breast cancer risk. This finding was subsequently observed in numerous other prospective studies.
Holmes, M. et al. Association of dietary intake of fat and fatty acids with risk of breast cancer. JAMA 281, 914–920 (1999).
Smith-Warner, S. A. et al. Types of dietary fat and breast cancer: a pooled analysis of cohort studies. Int. J. Cancer 92, 767–774 (2001).
Holmes, M. D. et al. Meat, fish and egg intake and risk of breast cancer. Int. J. Cancer 104, 221–227 (2003).
Frazier, A. L., Li, L., Cho, E., Willett, W. C. & Colditz, G. A. Adolescent diet and risk of breast cancer. Cancer Causes Control 15, 73–82 (2004).
Baer, H. J. et al. Adolescent diet and incidence of proliferative benign breast disease. Cancer Epidemiol. Biomarkers Prev. 12, 1159–1167 (2003).
Willett, W. C., Stampfer, M. J., Colditz, G. A., Rosner, B. A. & Speizer, F. E. Relation of meat, fat, and fiber intake to the risk of colon cancer in a prospective study among women. N. Engl. J. Med. 323, 1664–1672 (1990).
Bertone, E. R. et al. Dietary fat intake and ovarian cancer in a cohort of US women. Am. J. Epidemiol. 156, 22–31 (2002).
Byers, T. et al. American Cancer Society 2001 Nutrition and Physical Activity Guidelines Advisory Committee. American Cancer Society guidelines on nutrition and physical activity for cancer prevention: reducing the risk of cancer with healthy food choices and physical activity. CA Cancer J. Clin. 52, 92–119 (2002).
Colditz, G. A., Rosner, B. & for the Nurses' Health Study Research Group. Use of estrogen plus progestin is associated with greater increase in breast cancer risk than estrogen alone. Am. J. Epidemiol. 147, S64 (1998).
Rossouw, J. E. et al. Risks and benefits of estrogen plus progestin in healthy postmenopausal women: principal results from the Women's Health Initiative randomized controlled trial. JAMA 288, 321–333 (2002).
Rockhill, B., Colditz, G. & Rosner, B. Bias in breast cancer analyses due to error in age at menopause. Am. J. Epidemiol. 151, 404–408 (2000).
Chen, W. Y. et al. Association of hormone replacement therapy to estrogen and progesterone receptor status in invasive breast carcinoma. Cancer 101, 1490–1500 (2004).
Missmer, S. A., Eliassen, A. H., Barbieri, R. L. & Hankinson, S. E. Endogenous estrogen, androgen, and progesterone concentrations and breast cancer risk among postmenopausal women. J. Natl Cancer Inst. 96, 1856–1865 (2004). Shows that the endogenous hormones oestrogen, androgen and progesterone are most directly related to risk of oestrogen-receptor-positive breast cancers.
Pollak, M. N., Schernhammer, E. S. & Hankinson, S. E. Insulin-like growth factors and neoplasia. Nature Rev. Cancer 4, 505–518 (2004).
Hankinson, S. E. et al. Circulating concentrations of insulin-like growth factor-I and risk of breast cancer. Lancet 351, 1393–1396 (1998).
Toniolo, P. et al. Serum insulin-like growth factor-I and breast cancer. Int. J. Cancer 88, 828–832 (2000).
Muti, P. et al. Markers of insulin resistance and sex steroid hormone activity in relation to breast cancer risk: a prospective analysis of abdominal adiposity, sebum production, and hirsutism (Italy). Cancer Causes Control 11, 721–730 (2000).
Clevenger, C. V., Furth, P. A., Hankinson, S. E. & Schuler, L. A. The role of prolactin in mammary carcinoma. Endocr. Rev. 24, 1–27 (2003).
Hankinson, S. E. et al. Plasma prolactin levels and subsequent risk of breast cancer in postmenopausal women. J. Natl Cancer Inst. 91, 629–634 (1999).
Tworoger, S. S., Eliassen, A. H., Rosner, B., Sluss, P. & Hankinson, S. E. Plasma prolactin concentrations and risk of postmenopausal breast cancer. Cancer Res. 64, 6814–6819 (2004).
Hankinson, S. E. et al. Plasma sex steriod hormone levels and risk of breast cancer in postmenopausal women. J. Natl Cancer Inst. 90, 1292–1299 (1998).
Key, T., Appleby, P., Barnes, I., Reeves, G. Endogenous Hormones and Breast Cancer Collaborative Group. Endogenous sex hormones and breast cancer in postmenopausal women: reanalysis of nine prospective studies. J. Natl Cancer Inst. 94, 606–616 (2002).
Key, T. J. et al. Body mass index, serum sex hormones, and breast cancer risk in postmenopausal women. J. Natl Cancer Inst. 95, 1218–1226 (2003).
Haiman, C. A., Hankinson, S. E., Spiegelman, D., Brown, M. & Hunter, D. J. No association between a single nucleotide polymorphism in CYP19 and breast cancer risk. Cancer Epidemiol. Biomarkers Prev. 11, 215–216 (2002).
Guillemette, C. et al. Association of genetic polymorphisms in UGT1A1 with breast cancer and plasma hormone levels. Cancer Epidemiol. Biomarkers Prev. 10, 711–714 (2001).
Haiman, C. A. et al. The androgen receptor CAG repeat polymorphism and risk of breast cancer in the Nurses' Health Study. Cancer Res. 62, 1045–1049 (2002).
De Vivo, I., Hankinson, S. E., Colditz, G. A. & Hunter, D. J. A functional polymorphism in the progesterone receptor gene is associated with an increase in breast cancer risk. Cancer Res. 63, 5236–5238 (2003).
Ishibe, N. et al. Cigarette smoking, cytochrome P450 1A1 polymorphisms, and breast cancer risk in the Nurses' Health Study. Cancer Res. 58, 667–671 (1998).
De Vivo, I., Hankinson, S. E., Li, L., Colditz, G. A. & Hunter, D. J. Association of CYP1B1 polymorphisms and breast cancer risk. Cancer Epidemiol. Biomarkers Prev. 11, 489–492 (2002).
Gertig, D. M. et al. N-acetyltransferase 2 genotypes, meat intake and breast cancer risk. Int. J. Cancer 80, 13–17 (1999).
Schernhammer, E. S., Hankinson, S. E., Hunter, D. J., Blouin, M. J. & Pollak, M. N. Polymorphic variation at the -202 locus in IGFBP3: influence on serum levels of insulin-like growth factors, interaction with plasma retinol and vitamin D and breast cancer risk. Int. J. Cancer 107, 60–64 (2003).
Missmer, S. A. et al. A sequence repeat in the insulin-like growth factor-1 gene and risk of breast cancer. Int. J. Cancer 100, 332–336 (2002).
De Vivo, I. et al. A functional polymorphism in the promoter of the progesterone receptor gene associated with endometrial cancer risk. Proc. Natl Acad. Sci. USA 99, 12263–12268 (2002).
Rockhill, B. et al. A prospective study of recreational physical activity and breast cancer risk. Arch. Intern. Med. 159, 2290–2296 (1999).
Siiteri, P. K. Adipose tissue as a source of hormones. Am. J. Clin. Nutr. 45, S277–S282 (1987).
Cauley, J. A., Gutai, J. P., Kuller, L. H., LeDonne, D. & Powell, J. G. The epidemiology of serum sex hormones in postmenopausal women. Am. J. Epidemiol. 129, 1120–1131 (1989).
An, P. et al. A genetic study of sex hormone-binding globulin measured before and after a 20-week endurance exercise training program: the HERITAGE Family Study. Metabolism 49, 1014–1020 (2000).
Stoll, B. A. Adiposity as a risk determinant for postmenopausal breast cancer. Int. J. Obes. Relat. Metab. Disord. 24, 527–533 (2000).
Kaaks, R. Nutrition, hormones, and breast cancer: is insulin the missing link? Cancer Causes Control 7, 605–625 (1996).
Giovannucci, E. Insulin and colon cancer. Cancer Causes Control 6, 164–179 (1995).
Byrne, C. et al. Mammographic features and breast cancer risk: effects with time, age, and menopause status. J. Natl Cancer Inst. 87, 1622–1629 (1995).
Byrne, C. et al. Plasma insulin-like growth factor (IGF) I, IGF-binding protein 3, and mammographic density. Cancer Res. 60, 3744–3748 (2000).
Kawachi, I. et al. Smoking cessation in relation to total mortality rates in women: a prospective cohort study. Ann. Intern. Med. 119, 992–1000 (1993).
Fuchs, C. S. et al. Alcohol consumption and mortality among women. N. Engl. J. Med. 332, 1245–1250 (1995).
Hu, F. B. et al. Adiposity as compared with physical activity in predicting mortality among women. N. Engl. J. Med. 351, 2694–2703 (2004).
Willett, W. C. Nutritional Epidemiology 2nd edn (Oxford University Press, New York, 1998).
Wolf, A. et al. Reproducibility and validity of a self-administered physical activity questionnaire. Int. J. Epidemiol. 23, 991–999 (1994).
Manson, J. E. et al. A prospective study of walking as compared with vigorous exercise in the prevention of coronary heart disease in women. N. Engl. J. Med. 341, 650–658 (1999).
Hu, F. et al. Physical activity and risk of stroke in women. JAMA 283, 2961–2967 (2000).
Hu, F. et al. Walking compared with vigorous physical activity and risk of type 2 diabetes in women: a prospective study. JAMA 282, 1433–1439 (1999).
Hu, F. B., Li, T. Y., Colditz, G. A., Willett, W. C. & Manson, J. E. Television watching and other sedentary behaviors in relation to risk of obesity and type 2 diabetes mellitus in women. JAMA 289, 1785–1791 (2003).
Rimm, E. B. et al. Validity of self-reported waist and hip circumferences in men and women. Epidemiology 1, 466–473 (1990).
Hunter, D. J. et al. Cohort studies of fat intake and the risk of breast cancer: a pooled analysis. N. Engl. J. Med. 334, 356–361 (1996).
Hunter, D. J. et al. Non-dietary factors as risk factors for breast cancer, and as effect modifiers of the association of fat intake and risk of breast cancer. Cancer Causes Control 8, 49–56 (1997).
Pike, M. C., Krailo, M. D., Henderson, B. E., Casagrande, J. T. & Hoel, D. G. 'Hormonal' risk factors, 'breast tissue age' and the age-incidence of breast cancer. Nature 303, 767–770 (1983).
Rosner, B., Colditz, G. A. & Willett, W. C. Reproductive risk factors in a prospective study of breast cancer: the Nurses' Health Study. Am. J. Epidemiol. 139, 819–835 (1994).
Rosner, B. & Colditz, G. Log-incidence mathematical model of breast cancer incidence. J. Natl Cancer Inst. 88, 359–364 (1996).
Colditz, G., Rosner, B. & Speizer, F. Risk factors for breast cancer according to family history of breast cancer. J. Natl Cancer Inst. 88, 365–371 (1996).
Colditz, G. & Rosner, B. Cumulative risk of breast cancer to age 70 years according to risk factor status: data from the Nurses' Health Study. Am. J. Epidemiol. 152, 950–964 (2000).
Rockhill, B., Byrne, C., Rosner, B., Louie, M. M. & Colditz, G. Breast cancer risk prediction with a log-incidence model: evaluation of accuracy. J. Clin. Epidemiol. 56, 856–861 (2003).
Colditz, G., Rosner, B., Chen, W. Y., Holmes, M. & Hankinson, S. E. Risk factors for breast cancer: according to estrogen and progesterone receptor status. J. Natl Cancer Inst. 96, 218–228 (2004).
This work was supported by a grant from the National Cancer Institute. G.A.C. is supported in part by an American Cancer Society Clinical Research Professorship.
National Cancer Institute
- NESTED CASE–CONTROL STUDY
A study that is nested within a cohort study, whereby all cases and a small sample of non-cases are included — a design used frequently when genetic or other biomarker analyses are being conducted. It maintains the strengths of the prospective cohort (with exposure information collected before disease diagnosis) but is more efficient and economical because laboratory assays are conducted on only a small subset of the cohort.
- BUCCAL SAMPLES
Cheek-cell samples used as a source of DNA and collected by a swish-and-spit method using mouthwash, or by using a buccal brush.
- RADIAL SCARS
Benign lesions with a fibroelastic core from which ducts and lobules radiate.
- ONE-CARBON METABOLISM
The chemical reactions and physical changes involving compounds that contain a single carbon atom. One-carbon metabolism is crucial for nucleotide biosynthesis and for methylation reactions. Several dietary factors, including folate and vitamin B6, are important cofactors in this process.
- ENERGY ADJUSTMENT
A statistical technique to account for the influence of energy (calorie) intake when studying the association between a specific nutrient (for example, dietary fat) in relation to disease risk.
- RELATIVE RISK
A quantitative measure that is used to describe the increase (or decrease) in risk associated with a specific risk factor. A relative risk is the ratio of two absolute risks: the numerator is the absolute risk among those with the risk factor, while the denominator is the absolute risk among those without the risk factor.
- ABSOLUTE RISK
A person's chance of developing a specific disease over a specified time period. The absolute risk of disease is estimated by examining a large number of people who are similar in some respects (in terms of age, for example) and counting the number of individuals in this group who develop the disease over the specified time period.
- PROSPECTIVE COHORT STUDY
In prospective cohort studies, exposure information is collected from large groups of participants who are then followed over time to assess their health outcomes, and to determine how these outcomes are related to the previously collected exposure data.
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