An obese mum-to-be may be raising the risk of bowel cancer in her adult children


An obese mum-to-be may be raising the risk of bowel cancer in her adult children, suggests research of more than 18,000 mother and child pairs, published online in the journal Gut.

The findings suggest that conditions in the womb may be key risk factors for the disease and help to explain rising rates of the disease among younger adults, say the researchers.

In many high income countries, new cases and deaths from bowel cancer have fallen or plateaued in older adults, but have nearly doubled in younger adults, while these rates have risen rapidly across all age groups in low and middle income countries.

Consequently, the global burden of bowel cancer is expected to increase by 60% to more than 2.2 million new diagnoses and 1.1 million deaths by 2030.

Fetal programming is thought to be a factor in several health conditions across the life course, including cardiovascular disease and diabetes. Published research suggests that fetal exposure to obesity in the womb may also have a role in bowel cancer risk.

To explore this further, the researchers drew on more than 18,000 mother and child pairs from the Child Health and Development Studies (CHDS) at the Public Health Institute in Oakland, California, to see if maternal obesity, pregnancy weight gain, and high birthweight might be associated with a heightened risk of bowel cancer in adulthood.

At enrolment (1959-66), mothers provided background information, while details of prenatal visits, diagnosed conditions, and prescribed medications, were gleaned from their medical records, from 6 months before pregnancy through to delivery.

Mothers’ weight (BMI) was classified as: underweight (under 18.5); healthy (18.5–24.9); overweight (25– 29.9); and obese (30 or above).

Weight gain was recorded as the rate of early weight gain, or pounds gained each week up to and including 32 weeks of pregnancy; and total weight gain, or the difference between the last weight before giving birth and that recorded at the first prenatal visit.

Birthweight was categorised as low if 2000 g or below; average if between 2000 and 3999 g; and high as anything above that.

The offspring were then monitored for 60 years from birth until 2019 through linkage with the California Cancer Registry.

Most of the 18751 children (48%) were born in the early 1960s. About a third (34%) were racial/ethnic minorities, and half (52%) came from families with an annual income below the national average.

During the monitoring period, 68 were diagnosed with bowel cancer between 1986 and 2017, when aged between 18 and 56. About half (48.5%) were diagnosed before the age of 50. Nearly 1 in 5 had a family history of bowel cancer.

A higher proportion of obese (16%) mothers had offspring weighing 4000 g or more at birth than did underweight/healthy weight (7.5%) or overweight (11%) mothers.

Compared with being underweight or a healthy weight, overweight and obesity were associated with a more than doubling in the risk of bowel cancer in the offspring. Bowel cancer rates were 16.2/100,000, 14.8/100,000, and 6.7/100,000 in the adult offspring of obese, overweight, and underweight/healthy weight mothers, respectively.

While early weight gain wasn’t associated with bowel cancer risk, total weight gain was, with a doubling in risk for a gain of 23-29 pounds.

However, a high rate of early weight gain was associated with a quadrupling in risk among the offspring of mothers whose total weight gain had been low, but not among those whose total weight gain had been high.

The risk was also heightened among those whose birthweight was 4000 g or more compared with those within a healthy weight range at birth.

This is an observational study, and as such, can’t establish cause. Factors common to both mother and child, such as diet and microbiome, which weren’t captured in the CHDS, may have influenced the results. Similarly, offspring weight wasn’t measured throughout adulthood.

But the findings suggest that “the well-established relationship between obesity and colorectal cancer may have origins in periods that begin before birth,” say the researchers.

Nutrients received in the womb may permanently alter the structure and function of adipose (fat) tissue, appetite regulation and metabolism, while excess exposure to insulin and growth hormone may affect insulin sensitivity, they explain.

“Our results provide compelling evidence that in utero events are important risk factors of [colorectal cancer] and may contribute to increasing incidence rates in younger adults,” they write, adding: “There may also be other as yet unknown exposures during gestation and early life that give rise to this disease and warrant further study.”

“Given population trends in maternal obesity, which has multiplied in prevalence by nearly six since the 1960s, we may see a growing burden of early-onset [bowel cancer] for decades to come,” they conclude.

Childhood obesity has reached epidemic proportions worldwide [1]. Obesity in childhood has a pronounced impact on subsequent health risks as it often tracks into adulthood and is associated with a higher risk of chronic diseases including type 2 diabetes [2]. Although immediate lifestyle intervention in the paediatric population is essential, mounting evidence has pointed to the first 1000 days of life (from conception to 2 years old) as a critical period for preventing childhood obesity [3, 4].

In the 2016 Commission on Ending Childhood Obesity report commissioned by the World Health Organization (WHO), appropriate prenatal care such as optimizing maternal nutrition was highlighted as a key strategy to prevent childhood obesity [5].

The Developmental Origins of Health and Diseases (DOHaD) concept posits that early life represents a window of opportunity to optimize health trajectory of the immediate offspring and subsequent generations. Indeed, exposure to severe (in response to famine) or mild (e.g. suboptimal macronutrient composition) in utero malnutrition has been associated with a higher risk of obesity/higher adiposity [6,7,8,9,10] and metabolic disorders such as type 2 diabetes [11] later in life. Furthermore, maternal over-nutrition has also been shown to have a long-term influence on the offspring, including a higher risk of childhood obesity and other metabolic disorders (recently reviewed in [12]).

Due to the complexity of human diet [13] and because individuals do not consume nutrients and foods in isolation, the effectiveness of public health messaging to influence eating behaviours could be improved by assessing diet in a more holistic way. One such approach is through the use of diet quality indices based on previous scientific evidence that summarizes several aspects of dietary intake either against dietary guidelines or in terms of biological mechanism [14].

Because maternal inflammatory markers are associated with higher offspring adiposity [15, 16], reducing maternal inflammation through dietary optimization [17, 18] may be a potential strategy to reduce childhood obesity risk. A dietary inflammatory index (DII) has been designed specifically to measure diet-related inflammatory potential.

DII likely captures a slightly different and narrower dimension of diet than a general dietary quality index, as suggested by only a moderate correlation between these indices [19].

Although maternal inflammation can be a mechanism through which maternal diet affects child health, other pathways such as epigenetic programming can also be responsible. Thus, by investigating maternal dietary inflammatory potential, we can infer the potential involvement of inflammation in our studied outcomes and make more specific dietary recommendations based on the DII if it does.

Most studies to date examining dietary quality or inflammatory potential and childhood adiposity have been conducted in a single country [20,21,22,23], potentially limiting generalizability because dietary habits could differ substantially across countries. These studies, in general, observed beneficial influence of higher maternal dietary quality and lower dietary inflammatory potential on offspring adiposity measures; however, one study reported null associations after adjusting for covariates [22].

We thus aimed to further elucidate the associations between maternal dietary quality, inflammatory potential and offspring adiposity outcomes through an individual participant data meta-analysis involving five countries.

A UK study that followed women from pre-conception through pregnancy showed that maternal dietary intakes and patterns changed little from before pregnancy to early and late pregnancy [24]. However, maternal diet at different stages of pregnancy could potentially differentially influence child outcomes, as such stages represent different phases of foetal growth and development. For example, foetal fat accretion starts only in late gestation [25].

We thus hypothesized that a pro-inflammatory and low-quality maternal diet is associated with a higher risk of childhood obesity, potentially with differential influences of maternal diet at different stages of preconception/pregnancy. Pre-conception diet has been increasingly associated with child outcomes, suggesting that there may be opportunities for interventions that change dietary patterns before conception to influence long-term child health [26].

Thus, in cohorts with available data, we also investigated potential influence of pre-pregnancy maternal dietary quality and inflammatory potential on childhood obesity.

reference link :

More information: Maternal obesity, pregnancy weight gain, and birth weight and risk of colorectal cancer, Gut (2021). DOI: 10.1136/gutjnl-2021-325001


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