National Institute of Environmental Health Sciences   —  National Institutes of Health   —  U.S. Department of Health and Human Services

The Sister Study

20th Anniversary Research Highlights

Key findings from the Sister Study are grouped around major themes. In addition to yielding insights about breast cancer, this research has also discovered other important information related to women's health.

Here are some of our most impactful scientific findings:

Air Pollution

  • Exposure to airborne metals linked to postmenopausal breast cancer

    Women who lived in areas of air pollution with higher levels of airborne cadmium, lead, and mercury were at a higher risk of developing postmenopausal breast cancer.

    White AJ, O'Brien KM, Niehoff NM, Carroll R, Sandler DP. Metallic air pollutants and breast cancer risk in a nationwide cohort study. exit disclaimer Epidemiology. 2019 Jan;30(1):20-8.

  • Radioactivity linked to estrogen receptor negative breast cancer

    Radon, which occurs naturally in the environment, can breakdown into radioactive particles that can mix with air pollution, allowing the radioactive isotopes to be inhaled. Researchers found that exposure to airborne radioactive particles, such as emitted in radon gas, was associated with a higher risk of estrogen receptor negative breast cancer.

    White AJ, Gregoire AM, Fisher JA, Medgyesi DN, Li L, Koutrakis P, Sandler DP, Jones RR.Exposure to particle radioactivity and breast cancer risk in the Sister Study: A U.S.-wide prospective cohort. exit disclaimer Environmental Health Perspectives. 2022 Apr;130(4):47701. Epub 2022 Apr 4.

  • Exposure to nitrogen dioxide associated with some forms of breast cancer

    Exposure to nitrogen dioxide (NO2), a marker of traffic-related pollution, was associated with estrogen receptor or progesterone receptor positive breast cancer. The findings suggest that the association between air pollution and breast cancer may differ by subtype.

    Reding KW, Young MT, Szpiro AA, Han CJ, DeRoo LA, Weinberg C, Kaufman JD, Sandler DP.Breast cancer risk in relation to ambient air pollution exposure at residences in the Sister Study cohort. exit disclaimer Cancer Epidemiology, Biomarkers & Prevention. 2015 Dec;24(12):1907-9. Epub 2015 Oct 13.

  • Wood-burning stoves or fireplaces increases risk of breast cancer

    Indoor burning of fuel for heating or cooking is known to release carcinogens. Researchers found that women who were exposed to indoor air pollution from wood-burning stoves or fireplaces were more likely to develop breast cancer.

    White AJ, Sandler DP.Indoor wood-burning stove and fireplace use and breast cancer in a prospective cohort study. exit disclaimer Environmental Health Perspectives. 2017 July 18;125(7):077011.

  • Exposure to gasoline or petroleum products linked to premenopausal breast cancer

    Women with higher workplace exposure to gasoline or petroleum products were more likely to develop breast cancer than those with no reported exposure. Additionally, workplace exposure to soldering materials was associated with an increased risk of premenopausal breast cancer.

    Ekenga CC, Parks CG, Sandler DP.Chemical exposures in the workplace and breast cancer risk: a prospective cohort study. exit disclaimer International Journal of Cancer. 2015 Oct 1;137(7):1765-74. Epub 2015 Apr 27.

  • Exposure to airborne metals could increase risk of high blood pressure

    Women who lived in areas with higher levels of arsenic, lead, chromium, cobalt, or manganese in the air were more likely to have hypertension (high blood pressure).

    Xu J, White AJ, Niehoff NM, O'Brien KM, Sandler DP.Airborne metals exposure and risk of hypertension in the Sister Study. exit disclaimer Environmental Research. 2020 Dec;191:110144. Epub 2020 Sep 6.


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Obesity and Diabetes

  • Obesity protects against breast cancer in premenopausal women

    Obesity is a known risk factor for breast cancer in postmenopausal women but appears to be protective in premenopausal women. This protective effect is strongest for hormone receptor—positive breast cancer.

    Premenopausal Breast Cancer Collaborative Group, Schoemaker MJ, Nichols HB, Wright LB, Brook MN, Jones ME, O'Brien KM, Adami HO, Baglietto L, Bernstein L, Bertrand KA, Boutron-Ruault MC, Braaten T, Chen Y, Connor AE, Dorronsoro M, Dossus L, Eliassen AH, Giles GG, Hankinson SE, Kaaks R, Key TJ, Kirsh VA, Kitahara CM, Koh WP, Larsson SC, Linet MS, Ma H, Masala G, Merritt MA, Milne RL, Overvad K, Ozasa K, Palmer JR, Peeters PH, Riboli E, Rohan TE, Sadakane A, Sund M, Tamimi RM, Trichopoulou A, Ursin G, Vatten L, Visvanathan K, Weiderpass E, Willett WC, Wolk A, Yuan JM, Zeleniuch-Jacquotte A, Sandler DP, Swerdlow AJ.Association of body mass index and age with subsequent breast cancer risk in premenopausal women. exit disclaimer JAMA Oncology. 2018 Nov 1;4(11):e181771. Epub 2020 May 11.

  • Obesity increases risk of breast cancer in postmenopausal women

    Women who were overweight or obese and had one or more metabolic abnormalities (such as elevated triglycerides, high blood sugar, or high blood pressure) had increased risk of postmenopausal breast cancer, as did overweight or obese women with no metabolic abnormalities. Risk of postmenopausal breast cancer was also higher in women who had normal weight, but high measures of obesity in the mid-section of their body.

    Park YM, White AJ, Nichols HB, O'Brien KM, Weinberg CR, Sandler DP.The association between metabolic health, obesity phenotype and the risk of breast cancer. exit disclaimer International Journal of Cancer. 2017 Jun 15;140(12):2657-66. Epub 2017 Mar 7.

  • Type 2 diabetes increases risk of some types of breast cancer

    Researchers found no association between type 2 diabetes and the risk of developing estrogen receptor positive breast cancer, but they found a small increase in risk for estrogen receptor negative and triple negative breast cancer. Most women in the study with type 2 diabetes took metformin, a widely used diabetes medication. These results suggest that even if type 2 diabetes is associated with increased breast cancer risk overall, metformin may help reduce the risk of developing estrogen receptor positive breast cancer.

    Park YM, Bookwalter DB, O'Brien KM, Jackson CL, Weinberg CR, Sandler DP.A prospective study of type 2 diabetes, metformin use, and risk of breast cancer. exit disclaimer Annals of Oncology. 2021 Mar;32(3):351-9. Epub 2021 Jan 29.

  • Gestational diabetes increases risk of developing type 2 diabetes

    Developing diabetes during pregnancy (gestational diabetes), especially over multiple pregnancies, increases the risk of developing type 2 diabetes later in life.

    Diaz-Santana MV, O'Brien KM, Park YM, Sandler DP, Weinberg CR.Persistence of risk for type 2 diabetes after gestational diabetes mellitus. exit disclaimer Diabetes Care. 2022 Apr 1;45(4):864-70.


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Genes and DNA Modifications

  • Breast cancer genes linked to specific subtypes

    The Sister Study contributed to landmark research examining how several genes impact breast cancer risk in the general population. Variations in the BRCA1 and BRCA2 genes were associated with the highest risk of breast cancer, followed by variations in PALB2. Variations in the genes BARD1, RAD51C, and RAD51D were associated with increased risk of estrogen receptor negative and triple-negative breast cancer.

    Hu C, Hart SN, Gnanaolivu R, Huang H, Lee KY, Na J, Gao C, Lilyquist J, Yadav S, Boddicker NJ, Samara R, Klebba J, Ambrosone CB, Anton-Culver H, Auer P, Bandera EV, Bernstein L, Bertrand KA, Burnside ES, Carter BD, Eliassen H, Gapstur SM, Gaudet M, Haiman C, Hodge JM, Hunter DJ, Jacobs EJ, John EM, Kooperberg C, Kurian AW, Le Marchand L, Lindstroem S, Lindstrom T, Ma H, Neuhausen S, Newcomb PA, O'Brien KM, Olson JE, Ong IM, Pal T, Palmer JR, Patel AV, Reid S, Rosenberg L, Sandler DP, Scott C, Tamimi R, Taylor JA, Trentham-Dietz A, Vachon CM, Weinberg C, Yao S, Ziogas A, Weitzel JN, Goldgar DE, Domchek SM, Nathanson KL, Kraft P, Polley EC, Couch FJ.A population-based study of genes previously implicated in breast cancer. exit disclaimer The New England Journal of Medicine. 2021 Feb 4;384(5):440-51. Epub 2021 Jan 20.

  • Frequency of breast cancer genes do not vary by race

    In addition to the well-known breast cancer genes BRCA1 and BRCA2, other inherited genes are also important in breast cancer. In a large study that included Sister Study participants, investigators found that the frequencies of inherited genetic mutations in 12 breast cancer genes did not vary by race.

    Palmer JR, Polley EC, Hu C, John EM, Haiman C, Hart SN, Gaudet M, Pal T, Anton-Culver H, Trentham-Dietz A, Bernstein L, Ambrosone CB, Bandera EV, Bertrand KA, Bethea TN, Gao C, Gnanaolivu RD, Huang H, Lee KY, LeMarchand L, Na J, Sandler DP, Shah PD, Yadav S, Yang W, Weitzel JN, Domchek SM, Goldgar DE, Nathanson KL, Kraft P, Couch FJ.Contribution of germline predisposition gene mutations to breast cancer risk in African American women. exit disclaimer Journal of the National Cancer Institute. 2020 Dec 14;112(12):1213-21.

  • New breast cancer risk score could identify women at highest risk

    Researchers developed a new risk prediction score that may help identify women at higher risk for developing breast cancer. The new risk score is based on measures of naturally occurring chemical modifications to DNA, known as methylation, that can be assessed in the cells collected from a simple blood sample.

    Kresovich JK, Xu Z, O'Brien KM, Shi M, Weinberg CR, Sandler DP, Taylor JA.Blood DNA methylation profiles improve breast cancer prediction. exit disclaimerMolecular Oncology. 2022 Jan;16(1):42-53. Epub 2021 Aug 19.

  • Chemical modifications to DNA could predict risk of breast cancer

    Researchers examined more than 400,000 naturally occurring chemical modifications to DNA, known as DNA methylation markers, in Sister Study participants. They identified several thousand methylation markers associated with breast cancer. Because the associations were stronger for breast cancer diagnosed shortly after study enrollment, many of these markers may be indicators of early disease.

    Xu Z, Sandler DP, Taylor JA.Blood DNA methylation and breast cancer: A prospective case-cohort analysis in the Sister Study. exit disclaimerJournal of the National Cancer Institute. 2020 Jan 1;112(1):87-94. Epub 2019 Apr 15.

  • Biological age linked to elevated breast cancer risk

    Biologic age, a DNA-based estimate of a person's age, is associated with future development of breast cancer. Biologic age was determined by measuring DNA methylation, a chemical modification to DNA that is part of the normal aging process. Researchers found that for every five years a woman's biologic age was older than her chronologic or actual age, known as age acceleration, she had a 15 percent increase in her chance of developing breast cancer.

    Kresovich JK, Xu Z, O'Brien KM, Weinberg CR, Sandler DP, Taylor JA.Methylation-based biological age and breast cancer risk. exit disclaimerJournal of the National Cancer Institute. 2019 Oct 1;111(10):1051-8. Epub 2019 Feb 22.

  • Breast cancer treatments accelerate biological aging

    Researchers found that women who received breast cancer treatment, particularly radiation therapy, were biologically older than women who were never diagnosed with breast cancer.

    Kresovich JK, O'Brien KM, Xu Z, Weinberg CR, Sandler DP, Taylor JA. 2023.Changes in methylation-based aging in women who do and do not develop breast cancer. exit disclaimerJ Natl Cancer Inst, djad117.


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Hair Products

  • Adolescent use of straighteners and perms linked to breast cancer

    Researchers looked at hair product use during adolescence and found that frequent use of straighteners and perms may be associated with an increased risk of breast cancer, particularly the types of breast cancer that occur prior to menopause.

    White AJ, Gregoire AM, Taylor KW, Eberle C, Gaston S, O'Brien KM, Jackson CL, Sandler DP. Adolescent use of hair dyes, straighteners and perms in relation to breast cancer risk. exit disclaimerInternational Journal of Cancer. 2021 May 1;148(9):2255-63. Epub 2020 Dec 14.

  • Hair straightening products associated with ovarian cancer

    Frequent use of hair straightening products or relaxers (4 or more times per year) was associated with twice the risk of ovarian cancer compared to those who did not use the products. This finding is particularly relevant for Black women, who are more likely to use straighteners or relaxers.

    White AJ, Sandler DP, Gaston SA, Jackson CL, O'Brien KM. Use of hair products in relation to ovarian cancer risk. exit disclaimerCarcinogenesis. Sep;42(9):1189-95. Epub 2021 Jun 26.

  • Use of hair straighteners associated with uterine cancer

    Women who reported frequent use of hair straightening products (4 or more times per year), were more than twice as likely to develop uterine cancer compared to those who did not use these products. No associations were found between uterine cancer and use of hair dyes, bleach, highlights, or perms.

    Chang CJ, O'Brien KM, Keil AP, Gaston SA, Jackson CL, Sandler DP, White AJ. Use of straighteners and other hair products and incident uterine cancer. exit disclaimerJournal of the National Cancer Institute. 2022 Dec 8;114(12):1636-45. Epub 2022 Oct 17.


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Personal Care Products

  • Beauty, hair, and skin-related personal care products and breast cancer

    Among White women, those classified as "moderate" and "frequent" users of beauty products had increased risk of breast cancer relative to "infrequent" users, as did frequent versus infrequent users of skincare. Whether these results are due to specific chemicals or to other correlated behaviors needs to be evaluated.

    Taylor KW, Troester MA, Herring AH, Engel LS, Nichols HB, Sandler DP, Baird DD.Associations between personal care product use patterns and breast cancer risk among White and Black women in the Sister Study. exit disclaimerEnvironmental Health Perspectives. 2018 Feb 21;126(2):027011.

  • No association found between genital powder and uterine cancer

    Genital powders often contain talc and other substances that could potentially irritate and inflame tissues and promote cancer development in female reproductive organs. Researchers did not find an association between uterine cancer risk and genital powder use, with the possible exception of a slightly elevated risk among long-term users.

    O'Brien KM, Tworoger SS, Harris HR, Trabert B, Weinberg CR, Fortner RT, D'Aloisio AA, Kaunitz AM, Wentzensen N, Sandler DP.Genital powder use and risk of uterine cancer: A pooled analysis of prospective studies. exit disclaimerInternational Journal of Cancer. 2021 Jun 1;148(11):2692-701. Epub 2021 Jan 12.

  • Preliminary research did not find an association between douching and uterine cancer. However, there was some evidence that genital talc use may be associated with an increased risk of uterine cancer.

    O'Brien KM, D'Aloisio AA, Shi M, Murphy JD, Sandler DP, Weinberg CR.Perineal talc use, douching, and the risk of uterine cancer. exit disclaimerEpidemiology. 2019 Nov;30(6):845-52.

  • Potential link between genital powder and ovarian cancer

    Researchers found a small, but not statistically significant, association between genital powder use and ovarian cancer. The increase in risk may be limited to women who have not had a hysterectomy or tubal ligation.

    O'Brien KM, Tworoger SS, Harris HR, Anderson GL, Weinberg CR, Trabert B, Kaunitz AM, D'Aloisio AA, Sandler DP, Wentzensen N.Association of powder use in the genital area with risk of ovarian cancer. exit disclaimerJAMA. 2020 Jan 7;323(1):49-59.

  • Douching may increase risk of ovarian cancer

    Douching has been linked to elevated levels of urinary metabolites of endocrine-disrupting chemicals, which could affect cancer risk. Researchers found that douching was associated with increased risk of ovarian cancer.

    Gonzalez NL, O'Brien KM, D'Aloisio AA, Sandler DP, Weinberg CR.Douching, talc use, and risk of ovarian cancer. exit disclaimerEpidemiology. 2016 Nov;27(6):797—802. Epub 2016 Jun 20.


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Sleep

  • Artificial nighttime light associated with obesity

    Nighttime light is thought to affect health and wellbeing by disrupting the body's natural 24-hour (or circadian) rhythms. Exposure to artificial light while sleeping, including having a small nightlight or light from clock radios on in the room, light from outside the room or a light or television on inside the room, was associated with being overweight or obese.

    Park Y-MM, White AJ, Jackson CL, Weinberg CR, Sandler DP.Association of exposure to artificial light at night while sleeping with risk of obesity in women. exit disclaimerJAMA Internal Medicine. 2019 Jun 10;179(8):1061-71. Epub 2019 Jun 10.

  • Sleeping with indoor lights on may increase breast cancer risk

    Researchers found that sleeping with a television on or at least one light on in the bedroom was associated with a small increase (9%) in breast cancer risk. Living in an area with more outdoor light at night (such as from streetlamps or buildings) was not associated with an increased risk of breast cancer.

    White AJ, Weinberg CR, Park YM, D'Aloisio AA, Vogtmann E, Nichols HB, Sandler DP.Sleep characteristics, light at night and breast cancer risk in a prospective cohort. exit disclaimerInternational Journal of Cancer. 2017 Dec 1;141(11):2204-14. Epub 2017 Aug 22.


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Social and Lifestyle Factors

  • Earlier puberty increases breast cancer risk

    Earlier age at menarche (a woman's first menstrual period) and earlier age at thelarche (the start of breast development) were each associated with increased breast cancer risk. Experiencing both early menarche (before age 12) and early thelarche (before age 10) together was associated with a greater increase in risk than either factor on its own.

    Goldberg M, D'Aloisio AA, O'Brien KM, Zhao S, Sandler DP.Pubertal timing and breast cancer risk in the Sister Study cohort. exit disclaimerBreast Cancer Research. 2020 Oct 27;22(1):112. Epub 2020 Oct 27.

  • Recent childbirth can increase breast cancer risk

    Having children is widely recognized as a protective factor against breast cancer, but breast cancer risk may be increased shortly after childbirth. Researchers found that compared with women who never gave birth, women with one or more children had the highest risk of developing estrogen receptor positive breast cancer about 5 years after their last birth.

    Nichols HB, Schoemaker MJ, Cai J, Xu J, Wright LB, Brook MN, Jones ME, Adami HO, Baglietto L, Bertrand KA, Blot WJ, Boutron-Ruault MC, Dorronsoro M, Dossus L, Eliassen AH, Giles GG, Gram IT, Hankinson SE, Hoffman-Bolton J, Kaaks R, Key TJ, Kitahara CM, Larsson SC, Linet M, Merritt MA, Milne RL, Pala V, Palmer JR, Peeters PH, Riboli E, Sund M, Tamimi RM, Tjonneland A, Trichopoulou A, Ursin G, Vatten L, Visvanathan K, Weiderpass E, Wolk A, Zheng W, Weinberg CR, Swerdlow AJ, Sandler DP.Breast cancer risk after recent childbirth: A pooled analysis of 15 prospective studies. exit disclaimerAnnals of Internal Medicine. 2019 Jan 1;170(1):22-30.

  • Early-life trauma increases breast cancer risk

    Different types of early-life traumatic experiences may affect breast cancer risk. Researchers found that women who experienced either sexual trauma and household dysfunction or medium levels of early-life trauma had a greater risk of breast cancer. However, breast cancer risk due to early-life trauma was lower among women who reported constant childhood social support.

    Woo JMP, Simanek A, O'Brien KM, Parks C, Gaston S, Auer PL, Konkel RH, Jackson CL, Meier HCS, Sandler DP.Latent class models of early-life trauma and incident breast cancer. exit disclaimerEpidemiology. 2022 Sep 1;33(5):729-38. Epub 2022 May 16.

  • Disadvantaged neighborhoods associated with high blood pressure

    Women living in disadvantaged neighborhoods were more likely to have certain DNA "epigenetic" markers indicative of more rapid aging. This finding may help explain some of the biology underlying the relationship between poverty and poor health outcomes.

    Lawrence KG, Kresovich JK, O'Brien KM, Hoang TT, Xu Z, Taylor JA, Sandler DP.Association of neighborhood deprivation with epigenetic aging using 4 clock metrics. exit disclaimerJAMA Network Open. 2020 Nov 2;3(11):e2024329. Epub 2020 Nov 4.


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Diet and Supplements

  • Vitamin D may be useful for breast cancer prevention

    High blood vitamin D levels and regular vitamin D supplement use were both associated with a reduction in breast cancer risk. These associations were particularly strong among postmenopausal women.

    O'Brien KM, Sandler DP, Taylor JA, Weinberg CR.Serum vitamin D and risk of breast cancer within five years. exit disclaimerEnvironmental Health Perspectives. 2017 Jul 6;125(7):077004.

  • Some fruits and vegetables as well as vitamin supplements contain carotenoids, such as β-carotene, which may protect against chronic diseases including cancer. Researchers found that blood levels of several carotenoids were inversely associated with markers of inflammation and oxidative stress, suggesting that they may have antioxidant effects.

    Park YM, Lilyquist J, Van't Erve TJ, O'Brien KM, Nichols HB, Milne GL, Weinberg CR, Sandler DP.Association of dietary and plasma carotenoids with urinary F2-isoprostanes. exit disclaimerEuropean Journal of Nutrition. 2022 Aug;61(5):2711-23. Epub 2022 Mar 7.

  • Fruits and vegetables containing carotenoids may protect against cancer

    Diets that were considered pro-inflammatory and pro-oxidative stress were associated with higher risk of breast cancer, especially triple negative breast cancer. These results suggest that modifying dietary lifestyle factors may help reduce the risk of breast cancer.

    Park YM, Shivappa N, Petimar J, Hodgson ME, Nichols HB, Steck SE, Hébert JR, Sandler DP.Dietary inflammatory potential, oxidative balance score, and risk of breast cancer: Findings from the Sister Study. exit disclaimerInternational Journal of Cancer. 2021 Aug 1;149(3):615-26. Epub 2021 Mar 30.

  • Eating low-acidic foods, such as fruits and vegetables, may protect against breast cancer

    Eating acidic foods such as processed meats could promote carcinogenesis. Researchers showed that women with high diet-dependent acid loads had a greater risk of developing breast cancer than those with low acid loads. The finding suggests that diets with decreased acid load, such as those abundant in fruits and vegetables, may protect against breast cancer.

    Park YM, Steck SE, Fung TT, Merchant AT, Hodgson ME, Keller JA, Sandler DP.Higher diet-dependent acid load is associated with risk of breast cancer: Findings from the Sister Study. exit disclaimerInternational Journal of Cancer. 2019 Apr 15;144(8):1834-43. Epub 2018 Dec 7.


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