In the present nationwide study, which involved a large cohort of Korean individuals, we found that height was positively associated with risk of all sites-combined cancer and with cancers of the larynx, stomach, colorectum, pancreas, biliary tract and gallbladder, lung, liver, breast, ovary, cervix and corpus uteri, kidney, bladder, prostate, testes, CNS, thyroid, skin (excluding non-melanoma), and lymphatic and haematopoietic systems. The HR for all-site cancers per 5 cm increment in height was 1.09 (95% CI: 1.086–1.090), and the magnitude of the associations for specific sites ranged from HR 1.01 (95% CI: 1.00–1.02) for liver cancer to HR 1.18 (95% CI: 1.18–1.19) for thyroid cancer. This association was more prominent in women and non-smokers than in other counterparts.

Several studies have evaluated the association between attained stature and the risk for development of cancer,2,3,4,5,6,7 showed generalised outcomes, i.e., cancer risk increased with increase in stature. For instance, the Million Women Study,7 which is one of the largest studies, presented the positive associations between height and cancers in the colon, rectum, breast, endometrium, ovary, kidney, CNS, skin, and lymphatic and haematopoietic systems. In accordance with the result, our study showed significant associations for all above-mentioned sites. Furthermore, we newly reported positive relationships between taller stature and increased vulnerability to thyroid, gallbladder and biliary tract, and testicular cancers, which the Million Women Study did not report. A previous Korean study has also reported the association of greater stature with a higher risk of biliary cancers in line with our results.5 A recent Danish study has reported that the risk for testicular germ cell tumour was associated with height by age 7 years, not between ages 7 and 13.13 By contrast, the present study showed that taller adult height was significantly associated with a higher chance of testicular cancers in adults. A meta-analysis on the association between adult height and malignancy in testes showed a positive result.14

One of the possible mechanisms which link height to cancers is that the adult height correlates with organ sizes.15 According to this hypothesis, more active cell proliferation for the organs in taller persons could increase the possibility of mutation. Another explanation is an increased level of insulin-like growth factor (IGF) which correlates with calorie intake in animals,16 height in children,17 and risk of colorectal and prostate cancer in adult humans.18 In support of the IGF-malignancy link, there is a positive relationship of stature with carcinoma of the prostate and colorectum in several studies. Some genetic factors linked with height might share mechanisms underlying tumour vulnerability. Recently, Lophatananon et al.19 has reported that height and several genetic variants related to the human growth pathway, such as IGF or growth hormone secretagogue receptor,20 are associated with high-grade prostate cancer risk.

Although gastric, hepatic and cervical cancers traditionally thought to be related with infection, there have been some reports that obesity or metabolic syndrome are associated with the increased risk of them.21,22,23,24,25 For instance, hepatic cellular carcinoma can develop in noncirrhotic livers with non-alcoholic fatty liver disease, particularly in the presence of multiple metabolic risk factors, such as obesity and diabetes.23 Obese women might receive screening for cervical cancer less frequently than normal-weight women.25 Therefore, it is not possible to exclude the possibility that these tumours are linked to IGF hypothesis.

According to literature, the association of height with all-sites cancers was statistically significant after adjustment for potential confounding factors except for the current smoking and usage of hormone therapy.6,26 Our results confirmed that current smoking history is an important effect modifier; that is, height was more strongly related to cancer risk among non-smokers than among smokers.7,27 With regard to gender, similar associations in both genders have been reported.26 Slightly prominent associations among women than among men were shown in the present study. Given that this trend is maintained regardless of whether or not smoking, gender as well as smoking can be a modifier affecting the association between development of height and cancer. To date, no specific mechanism has been known as to whether the association between tall stature and the development of cancer is greater in women or non-smokers.

Another possible modifier is BMI. Weight is correlated with height and could confound the association between height and cancer.28,29 As for oesophageal cancer, which is negatively associated with BMI, the association with height was not significant.

There is some degree of consistency in the impact size of stature on site-specific cancer risks. For instance, melanoma, leukaemia, kidney cancer, and colorectal cancer have been ranked in the highest positions among both sexes.5,6,7,27 When the gender was restricted to men, the Whitehall cohort4 showed melanoma and kidney cancers were the most height-associated, while Sung et al.5 reported thyroid cancer, lymphoma, and melanoma as such. While only our study and the study by Sung et al.5 showed the highest association with taller stature in thyroid cancer, in the present study, skin cancers did not represent the strong association. Ethnic differences may have affected this result because thyroid cancer has been South Korea’s most common cancer, but skin cancers rarely occur in Korea.30 Additionally, a significant association with cancers in the biliary tract and taller persons has been reported in the above two studies. Even though the two studies were based in Korea, there were some differences in results; in the present study, persons with taller stature were at a higher risk of developing stomach and pancreas cancers, while in the study by Sung et al. there was no such clear association between height and stomach and pancreatic cancer.5 This could be because the two studies included in populations from different time periods; thus, resulting in a younger generation in our study. Heliobacter pylori, one of the most potent factors in the carcinogenesis of stomach cancer, is declining over time, from 66.9% in 1998 to 54.4% in 201117; Because H. pylori prevalence is decreasing in Korea and Japan, height may have a greater association with gastric cancer in younger individuals. On the other hand, malignancy in the pancreas has continuously increased, but the incidence is relatively low.30 A huge sample size of the present study could contribute the positive association unlike the study by Sung et al.5 Additionally, Sung et al. previously have shown a marked reduction in the positive association between height and liver cancer after an additional adjustment for hepatitis B viral antigenicity. Therefore, the significant association with liver cancer in taller persons in the present study should be interpreted cautiously because we did not adjust for hepatitis B or C viral antigenicity. Our results suggest a special caution when assessing the association of height with some cancers that are closely associated with weight or infection.

To determine the casualty between anthropometric traits and cancer, Mendelian randomisation study has been used.31 The basic concept is genetic factors influencing height play roles in carcinogenesis. One British study recently have reported that genetically determined taller height is causally associated with greater overall cancer susceptibility and cancer mortality by age 60.32 Further study is necessary to investigate which factors make the association or casualty greater among women or non-smoker.

One of the strengths of our present study is that we used the nationwide database for both sexes to perform a population-based cohort study. Some analyses involved small numbers of events for certain cancer sub-types; this reduced researchers’ ability to detect existing associations. To our knowledge, this is the first study that reported the positive relationship between adult height and cancers in testes among Asian population. This study evaluated as many as 23 site-specific cancers including and biliary tract and gallbladder.

The limitation of the present study is a short follow-up period and the lack of data about menstruation, parity, breast-feeding or use of exogenous hormones. Nonetheless, the result in this study is in accordance with previous studies with 10 years or more follow-up period7 and the consistent impact of height on the development of female organ cancers has been reported after controlling for reproductive factors.26 Authors did not exclude women who had undergone hysterectomy or bilateral oophorectomy at recruitment for the analyses of uterine and ovarian cancer.

Because the study participants were recruited based on health check-up examinee, it cannot be free from the potential selection bias. Further research on the exact mechanisms and potential lifestyle factors which may have a combined synergistic effect for the development of malignancies among individuals of taller stature could provide a clue for better cancer prevention.