BRCA mutation carriers have an increased risk of cancers from smoking

By Robyn Boyle, RPh, for MDLinx
Published January 29, 2018

Key Takeaways

Researchers in the multinational Hereditary Breast Cancer Clinical Study Group reported that cigarette smoking causes a modest increase in the risk of breast and ovarian cancers among women with a BRCA1 or BRCA2 mutation. The study was published in the International Journal of Cancer.

Although prior research into the risk of smoking and breast or ovarian cancer is not conclusive, cigarette smoking is a known carcinogen for certain types of cancer including lung, bladder, liver, and colon.

Women who inherit mutations in BRCA1 or BRCA2 genes have an increased risk of developing breast, ovarian, and other types of cancer. It is important to identify modifiable risks in this population so that carriers can be advised on how to reduce their chance of developing cancer.

In this large prospective study involving more 4,276 women, the Hereditary Breast Cancer Clinical Study Group assessed the risk of cigarette smoking and overall cancer incidence, as well as breast and ovarian cancer incidence in women with the BRCA1 and BRCA2 mutation from 80 centers in 17 countries from North America, Europe, Asia, the Caribbean, and Latin America. The research team was led by Kwang-Pil Ko, MD, PhD, from the Gachon University College of Medicine in Incheon, South Korea.

Using questionnaires, participants reported information such as smoking history, reproductive factors, and past medical history. Incidence of cancers were updated biennially during follow-up. During 26,711 person-years of follow-up, 700 cancers were reported.

The following smoking related variables were evaluated: smoking history (ever, never), current smoking history (non-smoker, past smoker, current smoker), starting age of smoking, and average packs smoked per week.

In general, women who smoked were older (40.4 years vs 38.1 years), more likely to be BRCA1 mutation carriers (78% vs 21%), more likely to have been pregnant (43% vs 31%), and breastfed longer compared to non-smokers.

Smokers were more likely to use oral contraceptives (42% vs 36%), to have a greater BMI (mean 24.7 vs 24.0 kg/m2), to live in Europe (52% vs 43%), and to consume alcohol (45% vs 28%) and coffee regularly (46% vs 24%) compared to never smokers. Average follow-up for smokers 6.5 years and nonsmokers was 6.1 years.

The breakdown in cancers between women with the BRCA1 and BRCA2 mutations was as follows:

BRCA1 (n=3,256)

BRCA2 (n=987)

All Cancers



Breast Cancer

339 (10.4%)

87 (8.8%)

Ovarian cancer

103 (3.2%)

6 (0.6%)

Other commonly diagnosed cancers included ductal carcinoma in situ, lobular carcinoma in situ, as well as cancers of the skin, peritoneum, and fallopian tube.

Women who had ever smoked had a 17% increased risk of developing any cancer compared to never smokers (hazard ratio [HR] = 1.17) and current smokers had a 31% increase risk of developing cancer compared to never smokers (HR = 1.31).

With regard specifically to risk of breast cancer, ever smoking was not significantly associated with increased risk (HR = 1.16); however, the risk in current smokers increased 28% (HR = 1.28). Women in the highest quartile of smoking duration and of total pack-years each had increased risk of developing breast cancer compared to never smokers (HR = 1.34 and HR = 1.33, respectively).

When evaluating the risk of ovarian cancer, the researchers found that past smokers had a 69% increased risk compared to never smokers (HR = 1.69). Current smoking was not significantly associated with risk (HR = 1.25). There was a significant dose-response relationship between both smoking duration and total pack-years and the risk of developing ovarian cancer.

The investigators admit that the study was limited by the use of a questionnaire to determine incidence of cancer and they were not able to confirm all reported cancers by medical record review. Furthermore, follow-up information was not available for 2,372 (36%) of the baseline participants, so cancer incidence was not determined.

“Findings from this large prospective analysis of smoking and BRCA-associated cancers clearly implicates smoking as a risk factor, particularly for breast and ovarian cancer, the most common type of cancers diagnosed in this high-risk population,” the authors concluded. “The adverse health effects of smoking should be discussed by clinicians and genetic counsellors managing women with BRCA-associated cancers.”

To read more about this study, click here

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