According to a population study, being overweight and obese in mothers during pregnancy increased the risk of colorectal cancer (CRC) in their children later in life.
Compared to underweight/healthy weight during pregnancy, both obesity and overweight were associated with an increased risk of CRC in the offspring (corrected HR 2.51, 95% CI 1.05-6.02 and adjusted HR 2.12, respectively). 95% CI 1.18-3.82), Caitlin Murphy, PhD, of the University of Texas Health Science Center at Houston, and colleagues reported.
Weight gain in early pregnancy also increased this risk, but only if weight gain was low throughout the pregnancy. This suggests that an aberrant fetal growth pattern from early to late pregnancy may affect outcomes later in life, the researchers wrote in Gut.
“We see that early life events, or things that happen in the womb, are important risk factors for colorectal cancer in adulthood,” Murphy told MedPage Today. “No one has really talked about early life factors that are important for this disease until now.”
It was “puzzling” to find that the effect of weight gain in early pregnancy on cancer risk in the offspring was dependent on a mother’s weight gain throughout the pregnancy, Murphy continued. “But it suggests there’s something about the timing of weight gain that’s important here,” she added.
The incidence and death rates of CRC have been rising in younger populations in recent decades, Murphy and colleagues noted. The global burden of disease is expected to increase by 60% by 2030, totaling 2.2 million new cases and 1.1 million deaths.
Obesity is a known risk factor for CRC, but it is still uncertain how obesity during pregnancy can predispose a fetus to developing disease later on. The researchers proposed two mechanisms: either maternal obesity drives obesogenic growth patterns for babies that persist into adulthood, or it triggers a sensitivity in fetal gastrointestinal tissue that can influence pathology into adulthood.
Murphy’s group analyzed the rates of CRC in adult offspring from the Child Health and Development Studies, a population-based cohort of mother-child couples who received prenatal care from Kaiser Permanente in Oakland in the 1960s. Offspring were followed for approximately 60 years.
Using data from the California State Cancer Registry, the researchers linked maternal body mass index (BMI), weight gain during pregnancy, and birth weight with diagnoses of CRC through the year 2019. They checked for covariates such as race and ethnicity, age of the mother at pregnancy. , parity, education level, total income, gestational age and family history of CRC.
More than 18,000 offspring were included in the analysis. Nearly half were born in the early 1960s and 52% were born to families whose total income was below the median. About two-thirds of the study participants were white.
During more than 700,000 person-years of follow-up, 68 offspring were diagnosed with CRC. All diagnoses occurred when the patients were between the ages of 18 and 56, with about half of the patients being diagnosed before the age of 50. Most patients were diagnosed with regional (44.1%) or distant (25%) disease, and with tumors in the distal colon (42.4%) or rectum (28.8%). Nearly 20% of patients had a family history of CRC.
For obese mothers, the incidence of CRC in offspring was 16.2 per 100,000 compared to 14.8 per 100,000 for overweight mothers and 6.7 per 100,000 for healthy-weight or underweight mothers.
Independently, neither early pregnancy weight gain nor overall pregnancy weight gain was significantly associated with the risk of CRC in the offspring. However, when there was a high pregnancy weight gain and a low overall weight gain, the risk of developing CRC for offspring in adulthood was much greater (adjusted HR 4.78, 95% CI 1.45-15.74).
Birth weight was also associated with increased CRC risk: infants weighing more than 4,000 g were more likely to develop CRC in adulthood (adjusted HR 1.95, 95% CI 0.8-4.38).
Murphy’s group acknowledged that shared maternal and child characteristics, including diet and microbiome, were not explained and may limit these findings. They also did not control for BMI in offspring throughout adulthood. Finally, gestational diabetes was not part of routine screening practice during recruitment and could have influenced these results.
Amanda D’Ambrosio is a reporter on the MedPage Today enterprise and research team. She covers obstetrics-gynecology and other clinical news, and writes articles about the US health care system. To follow
This study was funded by the National Cancer Institute.
Murphy and colleagues reported relevant relationships with Freenome, Bayer, Eisai, Genentech, Bristol Myers Squibb, Exelixis, Exact Sciences and GRAIL.