AJRCCM (IF=31) The evidence is here!

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The individual effects of early exposure to tobacco smoke and its interaction with genetic factors in adult lung cancer remain unclear

On August 9, 2022, Zhong Rong's team from Huazhong University of Science and Technology published online in the American Journal of Respiratory and Critical Care Medicine (IF=31) titled "In Utero and Childhood/Adolescence Exposure to Tobacco Smoke, Genetic Risk and Lung Cancer Incidence and Mortality in Adulthood", which included a total of 432,831 participants from the UK Biobank study

Lung cancer incidence was increased [hazard ratio (HR): 1.

Lung cancer is the second most common malignancy worldwide and the leading cause of cancer death, posing a huge public health burden
.

In 2020, it is estimated that there will be approximately 2.
2 million newly diagnosed lung cancer cases and approximately 1.
8 million lung cancer deaths globally in 2020, and will almost certainly rise further in the coming years
.

In view of this, significant efforts have been directed and continue to be expended to identify risk factors for lung cancer over the decades
.

It is well known that lung cancer can be driven by long-term interactions of predisposing genetic variants and environmental or behavioral factors
.

Smoking is a major environmental risk factor for lung cancer, causing approximately 7 million deaths globally each year, of which approximately 1.
7 million are due to lung cancer
.

Early life exposure has far-reaching health effects compared to exposure to tobacco smoke in adulthood, and available evidence suggests that early life processes, including prenatal, childhood and adolescence, have been implicated in susceptibility to a variety of environmental factors necessary window
.

At present, the prevalence of early exposure to tobacco is reported to be relatively high, with 8.
1% of women in the European region smoking during pregnancy and at least 50 million adult smokers globally who start smoking before the age of 15
.

Previous research has linked early exposure to tobacco smoke with autism, respiratory health and cancer in children
.

However, the association of early-life tobacco exposure (including in utero tobacco exposure and early initiation of smoking) with lung cancer morbidity and mortality later in life remains unclear
.

Part of the results of the article show (picture from American Journal of Respiratory and Critical Care Medicine)
In addition to environmental factors, genetic factors also play an important role in the pathogenesis of lung cancer
.

Previous genome-wide association studies (GWAS) have identified several genetic variants associated with lung cancer risk
.

The polygenic risk score (PRS) has been shown to increase the prediction of genetic susceptibility by weighing and integrating multiple single genetic variants with less impact
.

Studies have shown that PRSs constructed from GWAS gene variants can effectively predict cancer, including lung cancer risk and clinical outcomes
.

Considering the interaction between tobacco smoke exposure and genetic factors, it is particularly important to investigate the interaction and combined effects of in utero tobacco exposure with early smoking and PRS on lung cancer morbidity and mortality risk
.

In this study, it was hypothesized that in utero tobacco exposure and earlier initiation of smoking and its interaction with genetic factors may increase the risk of lung cancer morbidity and mortality in adulthood
.

The study utilized lung cancer cases from the UK Biobank (UKBB) prospective cohort study and constructed a PRS
.

This comprehensive dataset provides a unique opportunity to examine the interacting and combined effects of in utero and childhood/adolescent exposure to tobacco smoke and genetic factors on adult lung cancer morbidity and mortality
.

A total of 432,831 participants from the UK Biobank study were included in the study
.

The associations of in utero exposure to tobacco smoke, age at initiation of smoking, and their interaction with PRS, and adult lung cancer incidence and mortality were estimated using Cox proportional hazards models
.

Lung cancer incidence [hazard ratio (HR): 1.
59, 95% confidence interval (CI), 1.
44-1.
76] was increased among participants exposed to tobacco in utero
.

The multivariate-adjusted HRs (95% CI) for lung cancer incidence (compared with never-smokers) for smoking initiation in adulthood, adolescence, and childhood were 6.
10 (5.
25-7.
09), 9.
56 (8.
31-11.
00), and 15.
15 ( 12.
90- 17.
79) (trend < 0.
001)
.

Similar findings were observed in lung cancer mortality
.

Participants with high PRS and intrauterine tobacco exposure (compared to participants with low PRS not exposed in utero) had an HR of 2.
35 (95% CI, 1.
97-2.
80, Pinteraction=0.
089) for lung cancer incidence and a mortality rate of 2.
43 (95% CI, 2.
05-2.
88, Pinteraction=0.
032)
.

High PRS (compared with low PRS never smokers) who started smoking in childhood had an HR of 18.
71 (95% CI, 14.
21-24.
63, Pinteraction=0.
004) for incidence, and a mortality rate of 19.
74 (95% CI, 14.
98- 26.
01, Pinteraction= 0.
033)
.

In conclusion, exposure to tobacco smoke in utero and during childhood/adolescence and its interaction with genetic factors may significantly increase the risk of lung cancer morbidity and mortality in adulthood
.
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