Breast Cancer Risk Linked to Birth Size

LONDON, Sept. 30 (MedPage Today) -- Bigger babies may be at greater risk of breast cancer later in life, researchers affirmed.

Breast cancer risk rose 6% for every 2-cm increase in length, and 6% with each additional 1.1 pound of birth weight, reported Isabel dos Santos Silva, M.D., Ph.D., of the London School of Hygiene and Tropical Medicine, and colleagues online in PLoS Medicine.

In their patient-level meta-analysis, these significant associations were largely independent of adult body size and other postnatal factors.

Although the magnitude of the effect was small, it was similar to other common risk factors, such as age at menarche, age at menopause, or postmenopausal obesity, commented Pagona Lagiou, M.D., Ph.D., and Dimitrios Trichopoulos, M.D., Ph.D., both of the Harvard School of Public Health, in an accompanying comment.

If the relationship is causal, about 5% of all breast cancers in developed nations could result from large birth size, the researchers estimated.

While this could improve breast cancer prediction, it offers little opportunity for prevention, they acknowledged.

Because the many studies done offered conflicting conclusions on the birth size-breast cancer association, Dr. dos Santos Silva's group gathered patient-level data from the studies for a total of 22,058 breast cancer cases and 604,854 controls.

About half of the studies included were cohort studies with the rest mainly split between frequency- and individually-matched case-control studies.

Information on birth weight was from birth records, parental recall, or self-report by the women in adulthood.

Breast cancer risk increased with all measures of birth size except the ponderal index, a ratio of height to mass (P=0.81).

The increase in breast cancer risk was:

• 6% for each 0.5-kg increase in birth weight measured by birth records, which corresponded to about one standard deviation (P=0.002)
• 6% for each 2-cm increase in birth length, equivalent to one standard deviation (RR 1.06, 95% confidence interval 1.03 to 1.10)
• 9% for each standard deviation (1.5 cm) increase in head circumference (RR 1.09, 95% CI 1.03 to 1.15)

For head circumference, there was a U-shaped relationship with breast cancer.

Women with the largest head circumference of at least 35 cm at birth were at 11% higher risk relative to those in the baseline 33-cm category; those with a head circumference of less than 33 cm were 10% less likely to have breast cancer (P=0.01).

Birth length, though, was the strongest predictor of breast cancer risk among the birth size measures.

Women in the highest category for birth length -- 51 cm or longer -- were 17% more likely to develop breast cancer in adulthood than those of average length at birth (P=0.004).

Only birth length remained significantly linked to breast cancer risk when all the birth size components were mutually adjusted.

Studies that included only twins found even stronger relationships with all measures than seen in studies of singleton births, including a significant increase as ponderal index rose (RR 1.36, 95% CI 1.06 to 1.75).

But none of the associations were significant in women born prematurely or with a low birth weight.

Other factors later in life did not appear to account for the findings, which were consistent in women born across a period of several decades and wide geographical areas.

The associations were similar for pre- and postmenopausal breast cancer and were not explained away by maternal height and parity, the woman's adult height and body mass index, her socioeconomic status as an adult, or use of exogenous hormones. The researchers noted, though, that relatively few studies had data on these factors.

Some other types of cancer have also been weakly linked to birth size, Drs. Lagiou and Trichopoulos noted.

But the intrauterine environment may be most important in breast cancer because "the mammary gland seems to be the only organ that is not fully developed at birth," they said, "which implies that mammary tissue-specific stem cells may remain in a quiescent stage for longer periods than tissue-specific stem cells for other organs."

Maternal hormone exposure in utero may favor the generation of a greater number of susceptible stem cells with compromised genomic stability, they added.

The authors pointed out that residual or unmeasured confounding could not be excluded.

The study was funded by a grant and fellowship from Cancer Research UK.

The researchers did not disclose any financial conflicts of interests.

Drs. Lagiou and Trichopoulos reported support from the U.S. Department of Defense Breast Cancer Research Program but no conflicts of interest.

Additional source: PLoS MedicineSource reference: dos Santos Silva I, et al "Birth size and breast cancer risk: Re-analysis of individual participant data from 32 studies" PLoS Med 2008; 5: e193.Additional source: Lagiou P, Trichopoulos D "Birth size and the pathogenesis of breast cancer" PLoS Med 2008; 5: e194. Source reference: Lagiou P, Trichopoulos D "Birth size and the pathogenesis of breast cancer" PLoS Med 2008; 5: e194.