What can we learn from the association between adolescent alcohol consumption and breast cancer risk?

KEYWORDS:

• Timing
• adolescence
• life course

1. Introduction

Growing evidence points to the importance of early life exposures in later adult cancer risk. For example, studies have found obesity and physical inactivity in childhood and adolescence to be important drivers of risk for numerous adult onset cancers [1]. This includes many of those classified by the IARC as caused by adult weight gain (esophagus, gastric cardia, colon and rectum, liver, gallbladder, pancreas, postmenopausal breast, uterine, ovary, kidney (renal cell), meningioma, thyroid cancers, and multiple myeloma). Importantly, evidence shows that obesity in late adolescence and early adult years increases the risk of pancreatic cancer, colon cancer, and hematologic malignancies [2].

Alcohol is an established risk factor for multiple cancers, including breast, esophageal, liver, colorectal, and aerodigestive cancers [3,4]. Alcohol use is also common in youth, with around 30% of high school students drinking alcohol in the past month [5]. Does such exposure in this developmental stage result in unique cancer risks similar to those associated with obesity and physical inactivity?

2. The evidence on alcohol and breast cancer may provide insight

Alcohol is classified by the International Agency for Research on Cancer as a cause of breast cancer [6], with a 7%-10% increase in risk for each 10 g (approximately 1 drink) alcohol consumed daily by adult women [7–9]. This association is observed in both premenopausal and postmenopausal women. Compared with other organs, the breast appears to be more susceptible to the carcinogenic effects of alcohol. Approximately 4%-10% of breast cancers in the United States are attributable to alcohol consumption [7,10,11], accounting for 9,000–23,000 new invasive breast cancer cases each year.

Drinking patterns change over the lifetime, with a rapid increase in alcohol intake during adolescence leading to a peak in early adulthood. This is followed by a plateau in mid-life, and then a decline into older ages [12]. Nearly half of women of child-bearing age drink alcohol and 15% of drinkers in that age group binge drink – having four or more drinks at one time [13].

Data from the Nurses’ Health Study and Nurses’ Health Study II support links between alcohol intake in youth and young adulthood and later adult breast cancer risk. An analysis of the Nurses’ Health Study II found that for every 10 g/day of alcohol intake between menarche and first pregnancy, the risk of breast cancer increased 11% [11]. Results persisted after controlling for alcohol intake after pregnancies through adult life.

In the original Nurses’ Health Study cohort, a detailed analysis of timing of alcohol intake and breast cancer addressed drinking patterns and showed that binge drinking was positively associated with breast cancer risk [7]. This risk was on top of the risk associated with regular alcohol consumption. Further, intake in early adult life (ages 18–40) was significantly associated with increased risk of invasive breast cancer, with risk increasing with the average amount of alcohol consumed per day This risk persisted after controlling for alcohol consumption after age 40.

Benign breast lesions are a marker of increased risk of breast cancer and represent histologic changes of proliferation and stromal growth that are indicative of cancer risk [14]. Evidence on alcohol intake and increased risk of premalignant benign breast lesions adds further support of the role of alcohol both in the early mechanism of breast carcinogenesis and in the later steps of developing invasive breast cancer [7]. In prospective data from the Nurses’ Health Study II, increased risk of benign lesions (including those that carry the highest risk of subsequent breast cancer) was seen with alcohol intake. Each 10 g alcohol/day in adolescence was associated with a significant 15–16% increase in the risk of proliferative benign breast disease after controlling for alcohol intake after pregnancy [11,15]. The Growing Up Today Study, a cohort study which included girls ages 9–15 at baseline followed to age 27, alcohol intake was reported annually for 5 years, then every other year. Each additional drink per day resulted in a 50% increase in the risk of benign breast disease diagnosis in adolescence and young adulthood after controlling for current alcohol intake. Consumption of six or seven drinks per week was linked to a fivefold increase in risk compared to those who never drank [16].

3. Mechanisms

The specific mechanisms that could lead from adolescent alcohol consumption and breast cancer are currently unclear. Alcohol provides empty calories without any nutritional value; so, it is possible that consuming large amounts of alcohol may lead to a deficiency of essential nutrients, such as folate. Folate deficiency can cause human DNA damage and chromosome breaks, which could contribute to the increased risk of breast cancer [17]. Another possible pathway is through alcohol metabolism. Alcohol can cross biological membranes and be metabolized in breast tissue to acetaldehyde and reactive oxygen species [18]. Reactive oxygen species can react with and damage complex cellular molecules such as fats, proteins, or DNA ultimately leading to oxidative stress and breast tissue damage [18,19]. Alcohol intake during adolescence, with a peak in early adulthood, may lead to crucial and irreversible effects that impact later adult breast cancer risk. Though controlled for to some degree in most studies, alcohol intake is also associated with weight gain and adiposity [20], though BMI is inversely related in women it is positive in men and waist increases in both sexes. Adiposity and adult weight gain are both important risk factors for postmenopausal breast cancer. Finally, because it is difficult to tease out even in detailed analyses, there is the possibility that early life alcohol exposure may simply be a marker for cumulative lifetime exposure to alcohol. However, the quality of the current evidence suggests at least some level of independent impact of early life exposure on later adult risk.

Better describing the mechanisms through which adolescent alcohol consumption increases breast cancer risk, and its specific independent impact on risk, are crucial next steps for future research in this area.

And despite some preliminary results [21], data on the links between adolescent and young adult alcohol intake and cancers other than breast cancer remain sparse. However, given the rapid growth and development in adolescence and the susceptibility of cells and tissue during this period, it is a link well worth exploring. It likely some of the potential mechanisms linking adolescent drinking with breast cancer risk would likely relate to other cancers as well. In addition to standard epidemiological analyses, Mendelian randomization provides unique insight into causal links between youth exposure and later adult cancer [22]. A growing number of Mendelian Randomization studies support a causal relation between alcohol consumption and cancer [22], particularly colorectal and head and neck cancers.

4. Prevention

Curbing youth and young adult alcohol intake would have important short and long-term health benefits that reach well beyond cancer. More research is needed to determine effective, comprehensive, and multi-tier interventions, but there is currently good evidence that supports certain policy approaches, school-based interventions, and family interventions. Established areas of focus can include:

• Policy – Increases in alcohol taxes and implementation of minimal unit pricing [23–25]; improved ID checks; further limits on advertisements and promotions that reach youth; and use of warning labels on alcohol containers highlighting cancer risk [26].

• Education – Integration of effective alcohol messaging in school health curricula, particularly in the context of multiple health risk behavior interventions [27,28].

• Parents – Set rules about alcohol, monitor behavior, and have open discussions about alcohol as a family, including the short and long-term risks of alcohol and substance use [29].

Recent global reports have detailed the many health risks of alcohol consumption, including an increased risk of cancer. Studies of breast cancer and breast disease demonstrate that drinking in youth and young adulthood may bring unique, lifelong health risks. Better understanding such potential risks – and whether they apply to other cancers – can help develop policies and approaches to promote healthy alcohol intake not only in youth but also throughout all stages of life. Success on this front would have a profound impact on the health of individuals, the nation, and the world.

Declaration of interest

A Alimujiang reports receiving training funds from the University of Michigan School of Public Health. GA Colditz reports receiving general research support from the foundation for Barnes Jewish Hospital. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.